Neoadjuvant nivolumab (N) + platinum-doublet chemotherapy (C) for resectable NSCLC: 3-y update from CheckMate 816

Background The phase III CheckMate 816 study demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) with neoadjuvant N + C vs C in patients (pts) with resectable NSCLC. Here, we report 3-y efficacy, safety, and exploratory biomarker analyses from CheckMate 816. Methods Adults with stage IB (tumors >=4 cm)-IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS <= 1, and no known EGFR/ALK alterations were randomized to N 360 mg + C Q3W or C alone Q3W for 3 cycles followed by surgery. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS by surgical approach and extent/completeness of resection, and EFS and pCR by a 4-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline (BL) tumor samples. Results At a median follow-up of 41.4 mo (database lock, Oct 14, 2022), continued EFS benefit was observed with N + C vs C (HR, 0.68;95% CI, 0.49-0.93);3-y EFS rates were 57% and 43%, respectively. N + C improved EFS vs C in pts who had surgery, regardless of surgical approach or extent of resection, and in pts with R0 resection (table). Recurrence occurred in 28% and 42% of pts who had surgery in the N + C (n = 149) and C arms (n = 135), respectively. In the N + C arm, BL 4-gene inflammatory signature scores were numerically higher in pts with pCR vs pts without, and EFS was improved in pts with high vs low scores (data to be presented). Grade 3-4 treatment-related and surgery-related adverse events occurred in 36% and 11% of pts in the N + C arm, respectively, vs 38% and 15% in the C arm. Conclusions Neoadjuvant N + C continues to provide long-term clinical benefit vs C in pts with resectable NSCLC, regardless of surgical approach or extent of resection. Exploratory analyses in pts treated with N + C suggested that high BL tumor inflammation may be associated with improved EFS and pCR. Clinical trial identification NCT02998528. Editorial acknowledgement Medical writing and editorial support for the development of this , under the direction of the authors, was provided by Adel Chowdhury, PharmD, Samantha Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb. Legal entity responsible for the study Bristol Myers Squibb. Funding Bristol Myers Squibb. Disclosure P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, F-Star, G1 Therapeutics, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface;Financial Interests, Institutional, Research Grant: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus, Kyowa, Novartis, Regeneron;Financial Interests, Personal, Other, Trial steering committee member: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus;Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation;Non-Financial Interests, Personal, Advisory Role, Scientific advisory board member: LUNGevity Foundation. J. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, CLS Therapeutics, Merck, Protalix Biotherapeutics, Roche;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Protalix Biotherapeutics, Regeneron, Roche, Xenetic Biosciences;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, PeerView;Non-Financial Interests, Personal, Other, Data safety monitoring board member: Deutsche Forschungsgemeinschaft;Non-Financial Interests, Personal, Leadership Role, Industry chair: Canadian Association of Thoracic Surgeons. [Formula presented] N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Tak da, Owkin;Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen;Financial Interests, Institutional, Funding: BMS;Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG;Other, Personal, Other, Family member is an employee: AstraZeneca. M. Provencio: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Janssen, Pfizer, Roche, Takeda;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, Takeda. S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, Roche, Simcere, ZaiLab;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Hanosh, Roche. M. Awad: Financial Interests, Personal, Other, Consulting fees: ArcherDX, Ariad, AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, EMD Serono, Genentech, Maverick, Merck, Mirati, Nektar, NextCure, Novartis, Syndax;Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Genentech, Eli Lilly. T. Mitsudomi: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, BridgeBio Pharma;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, MSD, Novartis, Ono, Pfizer;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant, Invitae, Merck, MSD, Novartis, Ono, Pfizer, Taiho;Financial Interests, Personal, Advisory Board: AstraZeneca;Non-Financial Interests, Personal, Leadership Role, Former president: IASLC. E. Felip: Financial Interests, Institutional, Research Grant: Fundacion Merck Salud, Merck KGAa;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, MSD, Novartis, Peptomyc, Pfizer, Sanofi, Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck, MSD, PeerVoice, Pfizer, Sanofi, Takeda, touchONCOLOGY;Non-Financial Interests, Personal, Member of the Board of Directors: Grifols. S.J. Swanson: Financial Interests, Personal, Speaker's Bureau: Ethicon. F. Tanaka: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Chugai, Eli Lilly, Ono, Taiho;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Chugai, Ono;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Covidien, Eli Lilly, Intuitive, Johnson & Johnson, Kyowa Kirin, MSD, Olympus, Ono, Pfizer, Stryker, Taiho, Takeda. P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Cai: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb;Financial Interests, Personal, Other, Travel support for attending meetings and travel: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Neely: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Other, patents planned, issued, or pending: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.R. Broderick: Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by E sevier Inc.

Net treatment benefit of OSE2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO) in phase III Atalante-1 randomized trial

Background: OSE2101 (Tedopi) is an anticancer vaccine that increased overall survival (OS) (HR 0.59, p=0.017) versus Standard of Care Chemotherapy in the population of interest (PoI N=118) of patients with IO secondary resistance after sequential CT-IO (ESMO 2021 #47LBA). The Net Treatment Benefit (NTB) is an original method combining efficacy and safety endpoints to test the overall improvement in health outcome between 2 treatments (Buyse M. Stat Med 2010). NTB was assessed in the overall population (N=219) from whom OS improvement of OSE2101 (HR 0.86, p=0.35) was lower than in PoI. Methods: NTB was tested by comparing prioritized outcomes using Generalized Paired Wise Comparisons (GPC). The prioritized outcomes were OS, then time to worsening ECOG (threshold=2 months) followed by severe adverse events, progression free survival (shorter vs. longer than 2 months) and Quality of Life (threshold=5 points on Global Health Status of EORTC-QLQC30). Analysis was stratified using the 3 strata of the study (histology, best response to 1rst line, line of prior IO) and enrollment time (before vs during COVID-19). Sensitivity analyses used no stratification, different thresholds of clinical relevance and PoI. Results: In the primary analysis (1088 pairs), NTB was 19% and reached statistical significance in favor of OSE2101 (p=0.035). In unstratified analysis (11120 pairs), NTB was 11% (p=0.188). In the PoI (388 pairs), NTB was 22% (p stratified=0.074) and 28% (p=0.014) in unstratified analysis (3040 pairs). Although the primary analysis was statistically positive, results were not consistent in some sensitivity analyses due to the limited sample size and the impact of stratification factors. Conclusions: An overall improvement in health outcome was observed with OSE2101 in the overall population of advanced NSCLC after IO failure with a NTB of 19% over SoC. In PoI with IO secondary resistance after CT-IO, the NTB was 22%. Post-hoc analyses are ongoing intended to explain the variability of NTB and will be detailed. Clinical trial identification: EudraCT: 2015-003183-36;NCT02654587. Editorial acknowledgement: We thank Pierre Attali (Medical Expert, MD) for his support in the writing of the . Legal entity responsible for the study: Ose Immunotherapeutics. Funding: Ose Immunotherapeutics. Disclosure: M.E. Buyse: Financial Interests, Personal, Officer, Chief Scientific Officer: IDDI;Financial Interests, Personal, Invited Speaker, Board Member: CluePoints;Financial Interests, Personal, Stocks/Shares: IDDI, CluePoints. F. Montestruc: Financial Interests, Personal, Member of the Board of Directors, CEO of the Company: eXYSTAT SAS;Financial Interests, Institutional, Other, Statistician Consultant: AbbVie, Biocodex, Geneuro, Gensight, Guerbet, Imcheck, Ose Immunotherapeutics, Pfizer, Takeda;Non-Financial Interests, Personal, Other, Statistician Consultant and Training: Institut Pasteur. J. Chiem: Financial Interests, Personal, Full or part-time Employment: IDDI. V. Deltuvaite-Thomas: Financial Interests, Personal, Full or part-time Employment: IDDI. S. Salvaggio: Financial Interests, Personal, Full or part-time Employment, Working as a statistician: International Drug Development Institute. M.R. Garcia Campelo: Financial Interests, Personal, Advisory Role: Roche/Genentech, MSD Oncology, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, Janssen Oncology;Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, MSD Oncology, Sanofi/Aventis, Janssen Oncology, Amgen;Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche/Genentech, MSD Oncology, Pfizer. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD;Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, Galecto and MS . S. Viteri Ramirez: Financial Interests, Personal, Advisory Board: Merck Healthcare KGAA Germany, Bristol Myers Squibb S.A. U, Puma Biotechnology;Financial Interests, Personal, Invited Speaker: Takeda Farmaceutica España SA, MSD de España SA, AstraZeneca Farmaceutica Spain, Roche Farma SA;Financial Interests, Personal, Expert Testimony: Reddy Pharma Iberia SAU. W. Schuette: Financial Interests, Personal, Other, Honoraria: Roche, MSD, Novartis;Financial Interests, Personal, Advisory Role: Roche, MSD, Novartis. A. Zer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Takeda, Pfizer, Novartis;Financial Interests, Personal, Advisory Board: AstraZeneca, Steba, Oncohost;Financial Interests, Personal, Stocks/Shares: Nixio;Financial Interests, Institutional, Research Grant: BMS. S. Comis: Financial Interests, Personal, Full or part-time Employment: Ose Immunotherapeutics. B. Vasseur: Financial Interests, Personal, Full or part-time Employment: Ose Immunotherapeutics;Financial Interests, Personal, Other, Actions: Ose Immunotherapeutics. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Seattle Genetics, Pfizer, Takeda, Regeneron, MSD, Bristol Myers-Squibb, PharmaMar, Bayer;Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Foundation Medicine;Financial Interests, Personal, Expert Testimony: Novartis;Financial Interests, Personal and Institutional, Invited Speaker: Roche, AstraZeneca, MSD, Amgen, Celon Pharma, Pfizer, Novartis, Brsitol Myers-Squibb, Eli Lilly, Loxo;Financial Interests, Invited Speaker: BeiGene, Ardigen, Ose Immunotherapeutics;Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma;Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche;Other, Travel: Roche, Bristol Myers-Squibb, AstraZeneca. G. Giaccone: Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Institutional, Research Grant: Karyopharm. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Medical Trends, Merck Sharp & Dohme, Pfizer, Puma, Sanofi, Takeda, Merck Serono, Peptomyc, Regeneron, Syneos Health, F. Hoffmann-La Roche;Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Springer, Touch Medical, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono;Financial Interests, Personal, Invited Speaker, Independent member: Grifols;Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol-Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc;Non-Financial Interests, Leadership Role, President Elect (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica);Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO;Non-Financial Interests, Leadership Role, Member of Board of Directors and the Executive Committee (2017-Sept 2021): IASLC (International Association for the Study of Lung Cancer);Non-Fina cial Interests, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). All other authors have declared no conflicts of interest.

The acute phase response identifies cancer patients with adverse outcomes from SARS-CoV-2 infection as quantified by the OnCovid Inflammatory Score

We sought to determine parameters of the acute phase response, a feature of innate immunity activated by infectious noxae and cancer, deranged by Covid-19 and establish oncological indices' prognostic potential for patients with concomitant cancer and Covid-19. Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive referrals of patients with cancer and Covid-19 aged 18 from the U.K., Spain, Italy, Belgium, and Germany. Patients with myeloma, leukemia, or insufficient data were excluded. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) were evaluated for their prognostic potential, with the NLR, PLR, and PNI risk stratifications dichotomized around median values and the pre-established risk categorizations from literature utilized for the mGPS and PI. 1,071 eligible patients were randomly assorted into a training set (TS, n=529) and validation set (VS, n=542) matched for age (67.9±13.3 TS, 68.5±13.5 VS), presence of 1 comorbidity (52.1% TS, 49.8% VS), development of 1 Covid-19 complication (27% TS, 25.9% VS), and active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS). Among all 1,071 patients, deceased patients tended to categorize into poor risk groups for the NLR, PNI, mGPS, and PI (P<0.0001) with a return to pre-Covid-19 diagnosis NLR, PNI, and mGPS categorizations following recovery (P<0.01). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, P<0.0001), PNI<40 (46.6% vs 20.9%, P<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, P<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, P<0.0001). Findings were confirmed in the VS (P<0.001 for all comparisons). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (P<0.001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed the NLR (P<0.0001), PNI (P<0.0001), PI (P<0.01), and mGPS (P<0.001) as predictors of survival. In a multivariable Cox regression model including all inflammatory indices and pre-established prognostic factors for severe Covid-19 including sex, age, comorbid burden, malignancy status, and receipt of anti-cancer therapy at Covid-19 diagnosis, the PNI was the only factor to emerge with a significant hazard ratio [HR] in both TS and VS analysis (TS HR 1.97, 95%CI 1.19-3.26, P=0.008;VS HR 2.48, 95%CI 1.47- 4.20, P=0.001). We conclude that systemic inflammation drives mortality from Covid-19 through hypoalbuminemia and lymphocytopenia as measured by the PNI and propose the PNI as the OnCovid Inflammatory Score (OIS) in this context.

LBA47 Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO): Final results of phase III Atalante-1 randomised trial

Background: OSE2101 (Tedopi®) is an anticancer vaccine (modified epitopes restricted to HLA-A2+ from 5 tumor-associated antigens). Atalante-1 is a randomized phase 3 trial of OSE2101 vs Standard of Care (SoC docetaxel or pemetrexed) in pretreated HLA-A2+ patients with advanced NSCLC, with IO as last treatment. Methods: EGFR and ALK negative NSCLC patients, ECOG PS 0-1 were randomized 2:1 to receive OSE2101 subcutaneously Q3W for 6 cycles, followed by maintenance Q8W for 1 year and Q12W until progression, versus SoC (docetaxel or pemetrexed Q3W). Primary endpoint was OS (initial hypothesis of HR 0.7 for 401 pts). Secondary endpoints were disease control rate (DCR), quality of life (QoL - EORTC QLQ-C30/LC13), and Progression free survival (PFS). Toxicities were reported using CTCAE 5.0. Positive pre-specified analyses (ESMO 2020 #1260MO) identified a Population of Interest (PoI) comprised by patients with IO secondary resistance defined as failure after a minimum of 12 weeks IO in sequential CT-IO patients. Due to the risk of COVID-19 pandemic on data integrity, the study was stopped prematurely following IDMC recommendations. PoI was chosen as primary population for the final analysis. Results: 219 pts were enrolled: median age 65 years, 29% female, 10% never-smoker, 70% non-squamous. 183 (84%) pts received sequential CT-IO from whom 118 pts (54%) complied with the definition of PoI, with otherwise similar characteristics that the overall population. In PoI, mOS was 11.1 mo for OSE2101 vs 7.5 for SoC [HR 0.59 (0.38-0.91) p= 0.02]. 6 mo-DCR 25% vs 24% (NS), mPFS 2.7 mo vs 3.4 (NS), ORR 8% vs 18% (p=0.07). Post progression survival was 7.7 mo vs 4.6 [HR 0.46 p= 0.004], time to worsening ECOG PS 8.6 mo vs 3.3 [HR 0.45 p= 0.0005]. In the total population, HR for OS was 0.86 (0.62-1.19) p=0.36. QoL Global Health Status was maintained for OSE2101 (p<0.05). Severe Adverse Events were 38% vs 68% (p<0.001). There was no TEAE of concern in the OSE2101 group. Conclusions: OSE2101 had a favorable benefit/risk of versus SoC in advanced HLA-A2+ NSCLC patients. HR for OS improved from 0.86 to 0.59 in patients with secondary resistance to IO with a meaningful gain of median OS of 3.6 months with OSE2101. Clinical trial identification: EudraCT 2015-003183-36;NCT02654587. Editorial acknowledgement: We thank Pierre Attali (Medical Expert, MD), François Montestruc (Statistics, eXYSTATt) and Berangere Vasseur (MD, OSE Immunotherapeutics) for their support in the writing of the abstract. Legal entity responsible for the study: OSE Immunotherapeutics. Funding: OSE Immunotherapeutics. Disclosure: B. Besse: Financial Interests, Institutional, Research Grant: AbbVie;Financial Interests, Institutional, Research Grant: Amgen;Financial Interests, Institutional, Research Grant: AstraZeneca;Financial Interests, Institutional, Research Grant: BEIGENE;Financial Interests, Institutional, Research Grant: Blue Print Medicines;Financial Interests, Institutional, Research Grant: BMS;Financial Interests, Institutional, Research Grant: Boehringer Ingelheim;Financial Interests, Institutional, Research Grant: Cellgene;Financial Interests, Institutional, Research Grant: Cristal Therapeutics;Financial Interests, Institutional, Research Grant: Daiichi Sankyo;Financial Interests, Institutional, Research Grant: Eli Lilly;Financial Interests, Institutional, Research Grant: GSK;Financial Interests, Institutional, Research Grant: Inivata;Financial Interests, Institutional, Research Grant: Janssen;Financial Interests, Institutional, Research Grant: Onxeo;Financial Interests, Institutional, Research Grant: OSE Immunotherapeutics;Financial Interests, Institutional, Research Grant: Pfizer;Financial Interests, Institutional, Research Grant: Roche-Genentech;Financial Interests, Institutional, Research Grant: Sanofi;Financial Interests, Institutional, Research Grant: Takeda;Financial Interests, Institutional, Research Grant: Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: 4D Pharma;Financial Interests, Institutional, Res arch Grant: Aptitude Health;Financial Interests, Institutional, Research Grant: Cergentis. M.R. Garcia Campelo: Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: Bristol-Myers;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: Boehringer Ingelheim;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Lilly;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Advisory Role: MSD;Financial Interests, Personal, Advisory Role: Bristol-Myers;Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Boehringer Ingelheim;Financial Interests, Personal, Advisory Role: Pfizer;Financial Interests, Personal, Advisory Role: Novartis;Financial Interests, Personal, Advisory Role: AstraZeneca;Financial Interests, Personal, Advisory Role: Lilly;Financial Interests, Personal, Advisory Role: Takeda;Financial Interests, Personal, Advisory Role: Janssen;Financial Interests, Personal, Invited Speaker: MSD;Financial Interests, Personal, Invited Speaker: Bristol-Myers;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim;Financial Interests, Personal, Invited Speaker: Pfizer;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Lilly;Financial Interests, Personal, Invited Speaker: Takeda;Financial Interests, Personal, Invited Speaker: Janssen. E. Quoix: Financial Interests, Personal, Speaker’s Bureau: Shugaï;Financial Interests, Institutional, Principal Investigator: Roche;Financial Interests, Institutional, Principal Investigator: OSE Immunotherapeutics;Financial Interests, Institutional, Principal Investigator: Novartis;Financial Interests, Institutional, Principal Investigator: BMS;Financial Interests, Institutional, Principal Investigator: GSK. E. Felip: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Advisory Board: BeiGene;Financial Interests, Personal, Advisory Board: Boehringer Ingelheim;Financial Interests, Personal, Advisory Board: Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Eli Lilly;Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche;Financial Interests, Personal, Advisory Board: GlaxoSmithKline;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Advisory Board: Medical Trends;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Advisory Board: PEPTOMYC;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Puma;Financial Interests, Personal, Advisory Board: Regeneron;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Syneos Health;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Speaker’s Bureau: Amgen;Financial Interests, Personal, Speaker’s Bureau: AstraZeneca;Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb;Financial Interests, Personal, Speaker’s Bureau: Eli Lilly;Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche;Financial Interests, Personal, Speaker’s Bureau: Janssen;Financial Interests, Personal, Speaker’s Bureau: Medscape;Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme;Financial Interests, Personal, Speaker’s Bureau: Merck Serono;Financial Interests, Personal, Speaker’s Bur au: PeerVoice;Financial Interests, Personal, Speaker’s Bureau: Pfizer;Financial Interests, Personal, Speaker’s Bureau: Springer;Financial Interests, Personal, Speaker’s Bureau: Touch Medical;Financial Interests, Personal, Other, Independent Member of the Board: Grifols;Non-Financial Interests, Institutional, Research Grant: Grant For Oncology Innovation (GOI);Non-Financial Interests, Institutional, Research Grant: Fundación Merck Salud. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: AZ;Financial Interests, Personal, Invited Speaker: MSD;Financial Interests, Personal, Invited Speaker: BMS;Financial Interests, Personal, Invited Speaker: Pfizer;Financial Interests, Personal, Invited Speaker: Takeda;Financial Interests, Personal, Invited Speaker: Lilly;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: AZ;Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Advisory Board: Lilly;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: Sanofi. F. Denis: Financial Interests, Personal, Invited Speaker: Merck;Financial Interests, Personal, Invited Speaker: Chugai;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Roche. W. Hilgers: Financial Interests, Personal, Advisory Role: Janssen;Financial Interests, Personal, Advisory Role: AstraZeneca;Financial Interests, Personal, Invited Speaker: MSD. S. Viteri: FinancialInterests, Personal, Full or part-time Employment: Pangaea Oncology;Financial Interests, Personal, Advisory Board: AbbVie;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Institutional, Research Grant: Roche;Financial Interests, Institutional, Research Grant: AbbVie;Financial Interests, Institutional, Research Grant: OSE Immunotherapeutics;Financial Interests, Institutional, Research Grant: Merck;Financial Interests, Institutional, Research Grant: Janssen;Financial Interests, Institutional, Research Grant: Boehringer Ingelheim;Financial Interests, Institutional, Research Grant: Boston Pharmaceuticals;Financial Interests, Institutional, Research Grant: Exelexis;Financial Interests, Institutional, Research Grant: Novocure;Financial Interests, Institutional, Research Grant: Medimmune;Financial Interests, Personal, Other, Travel accomodation expenses: Roche;Financial Interests, Personal, Other, Travel accomodation expenses: Merck;Financial Interests, Personal, Other, Travel accomodation expenses: MSD;Financial Interests, Personal, Other, Travel accomodation expenses: BMS;Financial Interests, Personal, Other, Travel accomodation expenses: OSE Immunotherapeutics. W. Schuette: Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Lilly;Financial Interests, Personal, Advisory Role: Amgen;Financial Interests, Personal, Advisory Role: Merck. A. Zer: Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Invited Speaker: BMS;Financial Interests, Personal, Invited Speaker: MSD;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: Takeda;Financial Interests, Personal, Stocks/Shares: Nixio;Non-Financial Interests, Institutional, Research Grant: BMS. D. Costantini: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics;Financial Interests, Personal, Stocks/Shares: OSE Immunotherapeutics. R. Dziadziuszko: Financial Interests, Personal, Advisory Role: F. Hoffman- La Roche Ltd;Financial Intere ts, Personal, Advisory Role: AstraZeneca;Financial Interests, Personal, Advisory Role: Pfizer;Financial Interests, Personal, Advisory Role: Novartis;Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Role: Foundation Medicine Takeda;Financial Interests, Personal, Advisory Role: Seattle Genetics;Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Boehringer Ingelheim;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Principal Investigator: F. Hoffmann-La Roche Ltd;Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme;Financial Interests, Personal, Principal Investigator: Amgen;Financial Interests, Personal, Principal Investigator: Janssen;Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb;Financial Interests, Personal, Principal Investigator: AstraZeneca;Non-Financial Interests, Institutional, Product Samples: F. Hoffmann-La Roche Ltd;Non-Financial Interests, Institutional, Product Samples: Novartis;Non-Financial Interests, Institutional, Product Samples: Pfizer. All other authors have declared no conflicts of interest.

SERONCOVID: Seroconversion in solid-tumor cancer patients (p) after COVID-19 diagnosis

Background: Cancer p represent a high-risk population for severe COVID-19. Cancer-associated immunosuppression may hinder in the development of anti-SARS-CoV-2 antibodies. Methods: Data regarding baseline characteristics (age, cancer type, cancer activity, cancer treatment), COVID-19 infection and anti-SARS-CoV-2 IgG were collected from p with solid tumors who tested positive for COVID-19 (PCR+) between 10th March and 9th December 2020 at Catalan Institute of Oncology. We prospectively assessed anti-SARS-CoV-2 IgG seroprevalence at different timepoints (<2, 2-6, >6 months [m] since first PCR+) and explored factors associated with long-term IgG positivity. Results: Out of 79 registered p, 19 died without IgG testing (all of them <3 months after a PCR+), and 8 refused to participate, leaving 52 tested for IgG. Tested and not-tested p were similar according to baseline characteristics, cancer treatment and COVID-19. At the 1st timepoint, 19/23p were IgG+;at the 2nd, 29/33p were IgG+ and 1 inconclusive;at the 3rd timepoint, 18/22 were IgG+ (median time from PCR + to 3rd timepoint determination was 9.4 m (Interquartile range [IQR]: 8.5-9.7). Importantly, 1 p changed from IgG+ (2nd timepoint) to IgG- (3rd timepoint), and 1 inconclusive result (2nd timepoint) changed to negative (3rd timepoint). Potential factors associated to IgG+ >6 m are shown in the table. [Formula presented] Conclusions: High seroprevalence of anti-SARS-CoV-2 IgG was observed at several timepoints after COVID-19 diagnosis in solid tumor p. P with IgG+ at >6 m were older, and more likely to have required hospitalization and oxygen during prior COVID-19 in comparison to IgG- p >6m, suggesting that infection severity may promote durable immunity. Frequency of active cancer and active chemotherapy at COVID-19 diagnosis were higher among p with IgG- >6m, suggesting deeper immunosupression. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: E. Felip: Financial Interests, Personal, Other: Pfizer;Financial Interests, Personal, Other: Lilly;Financial Interests, Personal, Other: Eisai;Financial Interests, Personal, Other: Novartis;Financial Interests, Personal, Sponsor/Funding: Pfizer. M. Romeo Marin: Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: MSK;Financial Interests, Personal and Institutional, Other: MSD;Financial Interests, Personal and Institutional, Principal Investigator: AZ;Financial Interests, Personal and Institutional, Principal Investigator: GSK Tesaro;Financial Interests, Personal and Institutional, Principal Investigator: Merck. All other authors have declared no conflicts of interest.

Immune response after vaccination against SARS-COV-2 in lung cancer (LC) patients (p). Prospective study in the Medical Oncology Department at the Catalan Institute of Oncology-Badalona, Spain: COVID-lung vaccine

Background: With the approval of the vaccines against SARS-CoV-2, oncologic scientific societies have recommended cancer p to be prioritized for vaccination. Since cancer p have not participated in vaccine development studies, these recommendations arise some questions regarding their efficacy, safety and impact on survival. The aim of this prospective study is to evaluate the immune response to the SARS-CoV-2 vaccine in LC p. Secondary objectives include vaccine-related adverse events (AE), cancer treatment AE after vaccination, impact of the vaccine on survival, immune response, toxicity and survival outcomes in p>75 y, (re)infection after vaccination, complications and mortality. Methods: LCp who receive the vaccine against SARS-COV-2 are candidates to participate in this study. A pre-vaccination IgG determination will be performed to identify p with previous infection, but asymptomatic course. After vaccination, IgG will be repeated at 3, 6 and 12 months. Information on short and long term vaccine-related AEs will be collected, as well as, serological results, tumor and treatment-related data, and survival. Results: From March, 31 to April 15, 2021,106p have participated in the study. 58.5% were male, median age was 66 y (46- 83), 90.6% were Non-Small Cell LC, 83% has stage IV at diagnosis, Systemic therapy included EGFR/ALK/ROS1/RET/MET TKI (22.6%), immunotherapy (IT) (39.6%), chemotherapy (CT) (19.4%) and CTIT (14.1%). 4p were not receiving active therapy. 94.3% received Moderna® vaccine on behalf of the Hospital Vaccination Program. AES to 1st dose (1D) included local pain (16%), swelling (0.9%), fever (2.8%) and myalgia (0.9%). 5p had prior known COVID infection. No vaccine-related AE were reported in this group. 6p were admitted after vaccination due to cancer-related symptoms. No deaths were reported. Definitive data on baseline and 3-m serological data, as well as complete 1D and 2D related-AE and potential interactions with cancer therapy will be presented later. Conclusions: 1D of SARS-COV-2 vaccine appears to be safe irrespective of systemic therapy in our cohort of LCp. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: M. Saigí: Financial Interests, Institutional, Funding: Merck;Financial Interests, Personal, Other: BMS;Financial Interests, Personal, Other: Pfizer. E. Carcereny Costa: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Roche, Takeda;Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda, Amgen;Financial Interests, Personal, Other: Bristol-Myers Squibb, Pfizer, Roche, Takeda. M. Domenech: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS. A. Estival: Financial Interests, Personal, Other: Lilly, Pharmamar, Bayer, MSD, BMS, Roche. Honoraria: Roche, MSD, AstraZeneca, Pharmamar. M. Romeo Marín: Non-Financial Interests, Personal, Advisory Board: MSD, GSK;Non-Financial Interests, Personal, Other: AZ. M.T. Moran Bueno: Financial Interests, Personal, Advisory Board: AstraZeneca Boehringer Ingelheim Roche BMS. All other authors have declared no conflicts of interest.

SARS-CoV-2 antibody seroprevalence and safety of vaccines in cancer patients who recovered from COVID-19

Background: Little is known about natural anti-SARS-CoV-2 antibody seroprevalence post COVID-19 and safety of vaccines in COVID-19 survivors with cancer. Methods: Among 2795 consecutive patients (pts) with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined natural seroprevalence of anti-SARS-CoV-2 Antibodies (SC2Ab, IgM or IgG) in pts tested post-infection. We analysed prevalence and safety of SARS-Cov-2 vaccine administration in pts who underwent clinical re-assessment at participating institutions. Results: Out of 350 pts tested for SC2Ab, 318 (90.9%) had a positive SC2Ab titre post-convalescence. Neither baseline features (sex, age, comorbidities, smoking history, tumour stage/status, anticancer-therapy and primary tumour) nor COVID-19-specific features (complications, hospitalization, sequelae) were significantly associated SC2Ab status. Receipt of COVID-19 specific therapy was higher among SC2Ab+ pts (62.6% vs 40.6%, p=0.0156). Out of 593 pts with known vaccination status, 178 (30%) had received 1 dose, whilst 38 pts (6.4%) received 2 doses of mRNA based (70.2%) or viral vector vaccine (17.4%). Vaccinated pts were more likely aged ≥65 years (59% vs 48.3%, p=0.0172), with loco-regional tumour stage (56% vs 40.8%, p=0.0014), on anti-cancer therapy at COVID-19 (49.1% vs 38.2%, p=0.0168) and history of prior hospitalisation due to COVID-19 (61.8% vs 48.3%, p=0.0029). Vaccine-related adverse events were reported for 18/56 evaluable pts (32.1%) and included injection site reactions (50%), fever (44.4%), arthralgias (33.3%), fatigue (33.3%) and allergy (5.5%). No long-term vaccine-related morbidity was reported. Conclusions: We report high seroprevalence (>90%) of SC2Ab in convalescent cancer pts who survived COVID-19 irrespective of baseline demographics, oncological characteristics and COVID-19 severity. COVID-19 vaccines appear to be safe in cancer pts with history of prior infection. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: D.J. Pinato: Financial Interests, Personal, Invited Speaker: ViiV Healthcare;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Eisai;Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Nanostring tech. A. Cortellini: Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Advisory Board: SunPharma;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Astellas. All other authors have declared no conflicts of interest.

Time-dependent improvement in the clinical outcomes from COVID-19 in cancer patients: An updated analysis of the OnCovid registry

Background: Early reports from registry studies demonstrated high vulnerability of cancer patients from COVID-19, with case-fatality rates (CFR) >30% at the onset of the pandemic. With advances in disease management and increased testing capacity, the lethality of COVID-19 in cancer patients may have improved over time. Methods: The OnCovid registry lists European cancer patients consecutively diagnosed with COVID-19 in 35 centres from Jan 2020 to Feb 2021. We analysed clinical characteristics and outcomes stratified in 5 trimesters (Jan-Mar, Apr-Jun, Jul-Sep, Oct-Dec 2020 and Jan-Feb 2021) and studied predictors of mortality across 2 semesters (Jan-Jun 2020 and Jul 2020-Feb 2021). Results: At data cut-off, the 2634 eligible patients demonstrated significant time-dependant improvement in 14-days CFR with trimestral estimates of 29.8%, 20.3%, 12.5%, 17.2% and 14.5% (p<0.0001). Compared to the 2nd semester, patients diagnosed in the Jan-Jun 2020 time period were ≥65 (60.3% vs 56.1%, p=0.031) had ≥2 comorbidities (48.8% vs 42.4%, p=0.001) and non-advanced tumours (46.4% vs 56.1%, p<0.001). COVID-19 was more likely to be complicated in Jan-Jun 2020 (45.4% vs 33.9%, p<0.001), requiring hospitalization (59.8% vs 42.1%, p<0.001) and anti-COVID-19 therapy (61.7% vs 49.7%, p<0.001). The 14-days CFR for the 1st and 2nd semester was 25.6% vs 16.2% (p<0.0001), respectively. After adjusting for gender, age, comorbidities, tumour features, COVID-19 and anti-cancer therapy and COVID-19 complications, patients diagnosed in the 1st semester had an increased risk of death at 14 days (HR 1.68 [95%CI: 1.35-2.09]), but not at 3 months (HR 1.10 [95%CI: 0.94-1.29]) compared to those from the 2nd semester. Conclusions: We report a time-dependent improvement in the mortality from COVID-19 in European cancer patients. This may be explained by expanding testing capacity, improved healthcare resources and dynamic changes in community transmission over time. These findings are informative for clinical practice and policy making in the context of an unresolved pandemic. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: D.J. Pinato: Financial Interests, Personal, Speaker’s Bureau: ViiV Healthcare;Financial Interests, Personal, Speaker’s Bureau: Bayer;Financial Interests, Personal, Advisory Board: EISAI;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.

Phase Ib study evaluating BI 836880 (VEGF/Ang2 nanobody) in combination with ezabenlimab (BI 754091;anti-PD-1 antibody) in patients with solid tumours

Background: Combining anti-VEGF/Ang2 and anti-PD-1 therapy promotes an immunopermissive state, supportive of T-cell-mediated tumour cell destruction. This phase Ib study is assessing BI 836880 plus ezabenlimab in patients (pts) with advanced solid tumours. In Part 1 (dose escalation in pts with advanced NSCLC), the recommended phase 2 dose (RP2D) was determined as BI 836880 720 mg + ezabenlimab 240 mg IV q3w. Here, we report updated results, including data from Part 2 (expansion cohorts). Methods: Part 2 has 7 cohorts: metastatic (m) NSCLC after checkpoint inhibitor (CPI) monotherapy (Cohort A);mNSCLC after chemotherapy (CT) + CPI (Cohort B);mSCLC after CT ± CPI (Cohort C);recurrent GBM (1st and 2nd recurrence;Cohort D);immunotherapy-resistant m-melanoma (Cohort E);HCC after prior sorafenib or lenvatinib (Cohort F);and previously untreated unresectable HCC (Cohort G). Primary endpoint is objective response rate (complete response [CR] + partial response [PR]). Results: As of March 2021, 215 pts have been treated (Part 1: 14, Part 2: 201 [Cohort A, 35;B, 32;C, 19;D, 31;E, 32;F, 29;G, 23];70% male, median age 62 yrs). Any and ≥G3 AEs (any-cause) were reported in 183 (85%) and 72 (33%) pts. 118 (55%) pts had drug-related AEs, most commonly asthenia (13%) and hypertension (12%). 7 pts had G4 AEs (non-related hyperkalaemia + cardiac arrest, laryngospasm, gastrointestinal perforation;drug-related anaphylactic reaction, cholestatic hepatitis, acute pancreatitis, increased transaminases);9 pts had G5 AEs (non-related COVID-19 pneumonia, epilepsy, intracranial haemorrhage, cardio-respiratory arrest, haemoptysis, hepatic failure, general physical health deterioration, Glasgow coma scale abnormal + shortness of breath;drug-related tracheal haemorrhage). 35 (16%) pts had immune-related AEs and 15 (7%) had AEs leading to discontinuation. 179 pts were evaluable for response: 1 had confirmed CR (Cohort F), 22 had PR (Part 1: 2;Part 2: 20 [Cohort A, 4;C, 5;D, 4;E, 3;F, 3;G, 1]) and 110 had stable disease. 106 pts remain on treatment. Conclusions: BI 836880 plus ezabenlimab had a manageable safety profile, with preliminary activity in a range of tumour types. Clinical trial identification: NCT03468426. Editorial acknowledgement: Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Hannah Simmons MSc, of Ashfield MedComms, an Ashfield Health company, and funded by Boehringer Ingelheim. Legal entity responsible for the study: Boehringer Ingelheim. Funding: Boehringer Ingelheim. Disclosure: N. Girard: Financial Interests, Personal, Advisory Role: Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, BMS, MSD, Takeda, GSK, AbbVie, Pharmamar, Janssen, Sanofi;Financial Interests, Personal, Funding, Travel/accommodation/expenses: Roche, AstraZeneca, BMS MSD Oncology;Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Boehringer Ingelheim. M. Wermke: Financial Interests, Personal, Advisory Role: MSD, Novartis, Kite, Heidelberg Pharma, Roche, Boehringer Ingelheim;Financial Interests, Personal, Other, Honoraria: BMS, Merck, Roche, Novartis, Kite, Boehringer Ingelheim, AstraZeneca;Financial Interests, Personal, Funding, Travel/Accommodation/Expenses: Glenmark, BMS, AstraZeneca. E. Ledin: Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim. D. Kim: Financial Interests, Personal, Advisory Role: Health Insurance Review & Assessment Service, Korea;Financial Interests, Personal, Invited Speaker: Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Taiwan Lung Cancer Society;Financial Interests, Institutional, Principal Investigator, Clinical Trial Funding: Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer-Ingelheim, Bridge BioTherapeutics, Chong Keun Dang, Daiich-Sankyo, GSK, Hanmi, Janssen, Merus, MIrati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeuti;Non-Financial Interests, Person l, Advisory Role: Amgen, AstraZeneca, BMS / ONO Pharmaceuticals, Daiich-Sankyo, GSK, Janssen, Pfizer, SK Biopharm, Takeda, Yuhan;Non-Financial Interests, Personal, Member of the Board of Directors: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology;Other, Personal, Funding, Travel support for advisory board meeting attendance: Amgen, Daiichi-Sankyo. J. Bennouna: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, MSD, AstraZeneca, Roche, Servier, Bayer, AMGEN;Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, MSD, AstraZeneca, Roche;Financial Interests, Institutional, Research Grant: AstraZeneca. T. Lesimple: Financial Interests, Personal, Advisory Role: MSD, Novartis, BMS, Pierre Fabre;Financial Interests, Personal, Speaker’s Bureau: MSD, Novartis;Financial Interests, Institutional, Research Grant: Roche. E. Felip: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: BAYER;Financial Interests, Personal, Advisory Board: Beigene;Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim;Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Board: Eli Lilly;Financial Interests, Personal, Advisory Board: F. Hoffman-La Roche;Financial Interests, Personal, Advisory Board: Glaxo Smith Kline;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Advisory Board: Medical Trends;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Advisory Board: Peptomyc;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Puma;Financial Interests, Personal, Advisory Board: Regeneron;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Syneos Health;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Speaker’s Bureau: Amgen;Financial Interests, Personal, Speaker’s Bureau: AstraZeneca;Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb;Financial Interests, Personal, Speaker’s Bureau: Eli Lilly;Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche;Financial Interests, Personal, Speaker’s Bureau: Janssen;Financial Interests, Personal, Speaker’s Bureau: Medscape;Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme;Financial Interests, Personal, Speaker’s Bureau: Merck Serono;Financial Interests, Personal, Speaker’s Bureau: Peervoice;Financial Interests, Personal, Speaker’s Bureau: Pfizer;Financial Interests, Personal, Speaker’s Bureau: Springer;Financial Interests, Personal, Speaker’s Bureau: Touch Medical;Financial Interests, Personal, Member, Independent Member of the Board: Grífols. D. Berz: Financial Interests, Personal, Other, Honoraria: Oncocyte;Other, Personal, Other, Honoraria: Sun Pharma;Other, Personal, Other, Honoraria: Caris;Other, Personal, Other, Honoraria: Takeda;Other, Personal, Other, Honoraria: Natera;Other, Personal, Other, Honoraria: Jazz Pharma;Other, Personal, Other, Honoraria: Genentech;Financial Interests, Personal, Advisory Role: Oncocyte;Other, Personal, Advisory Role: Sun Pharma;Other, Personal, Advisory Role: Biocept;Other, Personal, Advisory Role: Prelude;Financial Interests, Personal, Speaker’s Bureau: Oncocyte;Other, Personal, Speaker’s Bureau: Caris;Other, Personal, Speaker’s Bureau: Sun Pharma;Other, Personal, Speaker’s Bureau: AstraZeneca;Other, Personal, Speaker’s Bureau: Takeda;Other, Personal, Speaker’s Bureau: Merck;Other, Personal, Speaker’s Bureau: Natera;Other, Personal, Speaker’s Bureau: Jazz Pharma. C. Mascaux: Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Astr Zeneca;Financial Interests, Personal, Advisory Role: Kephren;Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Role: MSD;Financial Interests, Personal, Advisory Role: Pfizer;Financial Interests, Personal, Other, Honoraria: Roche;Financial Interests, Personal, Other, Honoraria: AstraZeneca;Financial Interests, Personal, Other, Honoraria: Kephren;Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb;Financial Interests, Personal, Other, Honoraria: MSD;Financial Interests, Personal, Other, Honoraria: Pfizer;Financial Interests, Personal, Other, travel, accommodations, expenses: Roche;Financial Interests, Personal, Other, travel, accommodations, expenses: AstraZeneca;Financial Interests, Personal, Other, travel, accommodations, expenses: Boehringer Ingelheim;Financial Interests, Personal, Other, travel, accommodations, expenses: Takeda. M. Voskoboynik: Financial Interests, Personal, Advisory Role: AstraZeneca. H.T. Landsteiner: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. V. Chen: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. G. Jayadeva: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J. Alt: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, BMS, Pfizer, Roche, Takeda;Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, BMS, Roche;Financial Interests, Personal, Funding, Travel/accommodation/expenses: AstraZeneca, Boehringer Ingelheim, BMS. B. Hackanson: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, MSD, AstraZeneca, BMS. All other authors have declared no conflicts of interest.

Professional standing of young medical oncologists in Spain during COVID-19 pandemic: A nationwide survey by the Spanish Society of Medical Oncology (SEOM) +MIR Section

Background: Knowledge of the career paths and employment situation of young medical oncologists is lacking. The aim of our study was to evaluate the current professional standing of young medical oncologists during COVID-19 pandemic in Spain. Methods: The SEOM +MIR section conducted a national online survey in May 2021 of young medical oncology consultants (<6 years of expertise) and last year medical oncology residents. Using the electronic mailing available in the SEOM database, professionals from Spain were invited. Results: A total of 136 responses were eligible in the preliminary analysis. 86 (63%) were women. 106 (78%) were consultants and 30 (22%) were residents. 92 (68%) performed standard clinical care and 10 (7%) research activity. 97 (71%) were subspecialized in a main area of interest and almost half of them, 60 (48%), chose it because it was the only option available after residency. 75 (55%) had considered different employment opportunities other than standard clinical care and 33 (25%) showed an interest in increasing their research activity. 68 (50%) had considered working in foreign countries: 40 (29%) in the European Union. The main reasons were: 35 (26%) thought it might increase their professional development and 29 (22%) argued for better salary conditions abroad. Furthermore, 109 (80%) believed the professional standing in Spain was worse than other countries. After finishing their residency, only 20 (14%) were offered a job at their training hospital. Solely, 17 (12%) participants had an indefinite employment contract. 25 (18%) had previously signed a COVID-19 temporary contract. 55 (40%) were worried about their employment stability. Conclusions: The availability of subspecializing in medical oncology may depend on the job opportunity after residency rather than personal interest. The abundance of temporary contracts could have influenced the employment stability concerns observed. Our work contributes and is consistent with the ESMO values focused on the wellbeing of medical oncology professionals. Future mentoring strategies should engage in building a long-term career path for young medical oncologists. Legal entity responsible for the study: SEOM +MIR Section. Funding: Has not received any funding. Disclosure: V. Pacheco-Barcia: Financial Interests, Personal, Invited Speaker, Speaker Fee: Eisai;Financial Interests, Personal, Invited Speaker, Speaker Fee: Merck;Financial Interests, Personal, Invited Speaker, Speaker Fee: Bristol Myers Squibb;Financial Interests, Personal, Invited Speaker, Speaker Fee: LEO Pharma;Financial Interests, Personal, Invited Speaker, Speaker Fee: Kyowa Kirin;Financial Interests, Personal, Invited Speaker, Speaker Fee: Grunenthal;Financial Interests, Personal, Invited Speaker, Speaker FEE: Prostakan;Financial Interests, Personal, Invited Speaker, Speaker Fee: Lilly;Other, Other: Merck. D.A. Sanchez: Financial Interests, Personal, Invited Speaker: Janssen;Non-Financial Interests, Personal and Institutional, Leadership Role, National Representative of Young Doctors of Promotion of Employment in Organización Médica Colegial: Spanish Medical Association;Non-Financial Interests, Personal and Institutional, Leadership Role: President of the Murcian Health Service Company Committee;Non-Financial Interests, Personal and Institutional, Leadership Role: Vice-representative from the European Junior Doctors (EJD) in Oncology Section in UEMS (Uropean Union of Medical Specialties);Non-Financial Interests, Personal, Other: Member of +MIR Section of the Spanish Society of Medical Oncology;Non-Financial Interests, Personal, Other: ESMO member;Non-Financial Interests, Personal, Other: SEOM member. B. Obispo: Financial Interests, Personal, Invited Speaker: Lilly;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: Sanofi;Financial Interests, Personal, Invited Speaker: Fresenius;Financial Interests, Personal, Invited Speaker: Angelini Pharma;Financial Interests, Personal, Invited Speaker: Rovi;Financial Interes s, Personal, Invited Speaker: Leo Pharma. A. Quilez: Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Advisory Role: Clovis;Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb;Financial Interests, Personal, Speaker’s Bureau: GSK;Financial Interests, Personal, Advisory Role: GSK. A. Sesma: Financial Interests, Personal, Invited Speaker: MSD. D. Paez: Financial Interests, Personal, Advisory Role: Amgen;Financial Interests, Personal, Speaker’s Bureau: Amgen;Financial Interests, Personal, Speaker’s Bureau: F. Hoffman-La Roche Ltd;Financial Interests, Personal, Advisory Role: Sanofi;Financial Interests, Personal, Advisory Role: Ipsen;Financial Interests, Personal, Speaker’s Bureau: Advanced Accelerator Applications;Financial Interests, Personal, Research Grant, Research funding: Merck Serono. T. Quintanar Verduguez: Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Advisory Role: Novartis;Financial Interests, Personal, Invited Speaker: Abbott;Financial Interests, Personal, Invited Speaker: Nestle;Financial Interests, Personal, Advisory Role: Lilly;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Other, Consultancy: Astra Zeneca. M. Sánchez Cánovas: Financial Interests, Personal, Invited Speaker: Leo Pharma;Financial Interests, Personal, Invited Speaker: Angelini Pharma;Financial Interests, Personal, Invited Speaker: KyowaKirin;Financial Interests, Institutional, Other: Leo Pharma;Other, Personal, Other, Attending Symposia: Sanofi;Other, Personal, Other, Attending Symposia: MSD;Other, Personal, Other, Attending Symposia: Esteve;Other, Personal, Other, Attending Symposia: Amgen;Other, Personal, Other, Attending Symposia: Servier;Other, Personal, Other, Attending Symposia: Angelini;Other, Personal, Other, Attending Symposia: Leo Pharma;Other, Personal, Other, Educational Programs: Angelini;Other, Personal, Other, Educational Programs: Sanofi;Other, Personal, Other, Educational Programs: Rovi;Other, Personal, Other, Educational Programs: Leo Pharma;Other, Personal, Other, Educational Programs: Servier;Other, Personal, Other, Educational Programs: Merck;Other, Personal, Other, Remunerations for authorship: KyowaKirin;Other, Personal, Other, Remunerations for authorship: Mylan. N. Tarazona: Financial Interests, Personal, Invited Speaker: Amgen;Financial Interests, Personal, Invited Speaker: Servier;Financial Interests, Personal, Invited Speaker: Pfizer;Financial Interests, Personal, Invited Speaker: Merck;Financial Interests, Institutional, Principal Investigator, Principal Investigator: Mutua Madrileña;Financial Interests, Institutional, Principal Investigator: SEOM;Financial Interests, Institutional, Principal Investigator: TTD Group;Non-Financial Interests, Personal, Leadership Role, Member of CIBERONC Liquid Biopsy Working Module since 2018: CIBERONC;Non-Financial Interests, Personal, Leadership Role, Member of ESMO Translational Research and Precision Medicine Working Group for the period 2019-2020.: ESMO;Non-Financial Interests, Personal, Leadership Role, Member of ESMO-MCBS Extended Working Group since 2019: ESMO;Non-Financial Interests, Personal, Leadership Role, Member of ESMO faculty member for the Gastro-Intestinal Tumours faculty group for the period 2019-2023.: ESMO Faculty;Non-Financial Interests, Personal, Leadership Role, Member of Executive Committee SEOM +MIR 2020-2022.: SEOM +MIR. A. Fernandez Montes: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb;Financial Interests, Personal, Advisory Role: MSD;Financial Interests, Personal, Invited Speaker: MSD;Financial Interests, Personal, Invited Speaker: Servier;Financial Interests, Personal, Advisory Role: Lilly;Financial Interests, Personal, Invited Speaker: Lilly;Financial Interests, Personal, Advisory Role: Astra Zeneca;Financial Interests, Personal, Invited Speaker: Pierre Fabre;Financial Interests, Personal, Invited Speaker: Merck. E. Felip: Financial Interest , Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Advisory Board: Beigene;Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim;Financial Interests, Personal, Advisory Board: Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Eli Lilly;Financial Interests, Personal, Advisory Board: F Hoffman-La Roche;Financial Interests, Personal, Advisory Board: Glaxo Smith Kline;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Advisory Board: Medical Trends;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Advisory Board: Peptomyc;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Puma;Financial Interests, Personal, Advisory Board: Regeneron;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Syneos Health;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Speaker’s Bureau: Amgen;Financial Interests, Personal, Speaker’s Bureau: AstraZeneca;Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb;Financial Interests, Personal, Speaker’s Bureau: Eli Lilly;Financial Interests, Personal, Speaker’s Bureau: F Hoffman-La Roche;Financial Interests, Personal, Speaker’s Bureau: Janssen;Financial Interests, Personal, Speaker’s Bureau: Medscape;Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme;Financial Interests, Personal, Speaker’s Bureau: Merck Serono;Financial Interests, Personal, Speaker’s Bureau: Peervoice;Financial Interests, Personal, Speaker’s Bureau:Pfizer;Financial Interests, Personal, Speaker’s Bureau: Springer;Financial Interests, Personal, Speaker’s Bureau: Touch MEdical;Other, Personal, Other, Independent member of the board: GRIFOLS. A. Rodríguez-Lescure: Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Pfizer;Financial Interests, Personal, Advisory Role: Novartis;Financial Interests, Personal, Advisory Role: Lilly;Financial Interests, Personal, Advisory Role: MSD;Financial Interests, Personal, Advisory Role: Astra Zeneca;Financial Interests, Institutional, Funding: Roche;Financial Interests, Institutional, Funding: Novartis;Financial Interests, Institutional, Funding: Pfizer;Financial Interests, Institutional, Funding: Lilly;Financial Interests, Institutional, Funding: Astra Zeneca;Financial Interests, Institutional, Funding: Amgen;Financial Interests, Institutional, Funding: MSD;Financial Interests, Institutional, Funding: Bristol-Myers Squibb;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: Pfizer;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: Lilly;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: MSD;Financial Interests, Personal, Invited Speaker: Merck;Other, Personal, Other, Travel, accommodations: Roche;Other, Personal, Other, Travel, accomodations: Pfizer. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: Array Biopharma;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Advisory Board: Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Hoffman La- Roche;Financial Interests, Personal, Advisory Board: Merck serono;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Servier;Financial Interests, Institutional, Research Grant: Abbvie;Financial Interests, Institutional, Research Grant: Amgen;Financial Interests, Institutional, Research Grant: Array Pharmaceuticals;Financial Interests, Institution l, Research Grant: AstraZeneca;Financial Interests, Institutional, Research Grant: Boehringer Ingelheim;Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb;Financial Interests, Institutional, Research Grant: GlaxoSmithKline;Financial Interests, Institutional, Research Grant: Hoffman La-Roche;Financial Interests, Institutional, Research Grant: Medimmune;Financial Interests, Institutional, Research Grant: Merck Serono;Financial Interests, Institutional, Research Grant: MSD;Financial Interests, Institutional, Research Grant: Novartis;Financial Interests, Institutional, Research Grant: Pierre-Fabre;Financial Interests, Institutional, Research Grant: Sanofi Aventis. All other authors have declared no conflicts of interest.

Phase Ib study of BI 836880 (VEGF/Ang2 nanobody) plus ezabenlimab (BI 754091;anti-PD-1 antibody) in patients (pts) with solid tumors

Background: In preclinical studies, the combination of anti-VEGF/Ang2 and anti-PD-1 therapy has been shown to promote an immunopermissive state, which is supportive of T-cell-mediated tumor cell destruction. BI 836880 is a humanized bispecific nanobody that targets VEGF and Ang2, and ezabenlimab (BI 754091) is an anti-PD-1 antibody. Phase I studies investigating each as monotherapies have reported safety and preliminary antitumor activity. This ongoing Phase Ib study is evaluating the combination of BI 836880 and ezabenlimab in pts with advanced solid tumors. In Part 1 (dose escalation), the combination was feasible in pts with advanced NSCLC, with a recommended Phase II dose (RP2D) of BI 836880 720 mg + ezabenlimab 240 mg IV q3w. Here, we report updated results from Part 2 (expansion phase), which is assessing the antitumor activity and safety of the RP2D. Methods: Seven cohorts are currently recruiting pts in Part 2: metastatic (m) NSCLC after checkpoint inhibitor (CPI) monotherapy (Cohort A);mNSCLC after chemotherapy (CT) + CPI (Cohort B);mSCLC after CT ± CPI (Cohort C);1 and 2nd recurrences of glioblastoma (GBM;Cohort D);immunotherapy-resistant mmelanoma (Cohort E);hepatocellular carcinoma (HCC) after prior sorafenib or lenvatinib ± CPI (Cohort F);and previously untreated/unresectable HCC (Cohort G). Primary endpoint is objective response rate (complete response + partial response [PR]). Results: As of January 2021, 196 pts have received BI 836880 plus ezabenlimab (14 in Part 1, 182 in Part 2 [Cohort A, 26;B, 30;C, 19;D, 31;E, 32;F, 28;G, 16]). 134 (68%) pts were male, median age was 63 years and 102 (52%) had prior CPI use. Any grade and ≥G3 adverse events (AEs;any cause) were reported by 160 (82%) and 62 (32%) pts, most commonly (all%/ ≥G3%) hypertension (20/8), asthenia (20/3), diarrhea, decreased appetite, and nausea (all 11/1). 95 (48%) pts had a drug-related AE, most commonly hypertension and asthenia (both 11%). 6 pts had a G4 AE (non-related: hyperkalemia + cardiac arrest, laryngospasm, gastrointestinal perforation;drug-related: anaphylactic reaction, acute pancreatitis, transaminases increased);8 pts had a G5 AE (non-related: general physical health deterioration, epilepsy, hemoptysis, cardiorespiratory arrest, hepatic failure, intracranial hemorrhage, COVID-19 pneumonia;drugrelated tracheal hemorrhage). 30 (15%) pts had immune-related AEs (3% ≥G3), including hypothyroidism (3%). 11 (6%) pts had an AE leading to discontinuation. Overall, 145 pts were evaluable for response: 9 pts achieved confirmed PR (2 pts in Part 1 and 7 in Part 2 [NSCLC, n = 3;SCLC, n = 1;GBM, n = 1;melanoma, n = 1;and 2 -line HCC, n = 1]), 87 pts had stable disease and 49 pts had progressive disease. 111 pts remain on treatment. Conclusions: BI 836880 plus ezabenlimab had a manageable safety profile. The combination showed preliminary antitumor activity in a range of tumor types.

SER-ONCOVID: Seroconversion in solid-tumor cancer patients after COVID-19 diagnosis

Background: Cancer patients (pts) represent a high-risk population for severe COVID-19. Cancer-associated immunosuppression may hinder in the development of anti-SARS-CoV-2 antibodies. Methods: Data regarding baseline characteristics, COVID-19 and anti-SARS-Cov2 IgG were collected from cancer pts (solid tumors) who tested positive for COVID-19 (PCR+) between March and April 2020 at Catalan Institute of Oncology. We prospectively assessed anti-SARS-Cov2 IgG seroprevalence at 3 and 9 months post infection and explored clinico-pathologic factors associated with IgG positivity. We explored the impact of potential factors influencing antibody production at >9 months. Results: Of 49 pts registered between 10 March-26 April 2020, 21 died <3 months after the infection and 5 pts refused to participate, leaving 23 eligible pts for IgG testing. With respect to those not tested, IgG tested cohort was younger (median age: 64.0 vs 72.9 years, p = 0.001) and presented oncologic remission in 68.2% of cases (vs 34.6%, p = 0.043) at COVID-19 diagnosis. Median time from PCR+ to first and second IgG determination was 3.2 months (Interquartile range [IQR]: 2.9-4.1) and 9.5 months (IQR: 8.8-9.8), respectively. Out of 23 pts, 15 had both determinations and 8 had only one (3 in the first time point, 5 in the second one). We identified 16/18 pts IgG+ (88.9%) at 3 months and 17/20 pts IgG+ (85%) at 9 months. One IgG+ pt became IgG-at the second determination, one was IgG-at both timepoints, and one had an inconclusive result at the first but negative at the second timepoint. Key characteristics of patients by IgG result 9 months after COVID-19 diagnosis are shown in the table. Conclusions: We describe a high seroprevalence of anti-SARS-CoV-2 IgG at 3 and 9 months after COVID-19 diagnosis in solid tumour patients, irrespective of anti-cancer therapy exposure. Pts who were IgG+ at 9 months were older, and more likely to have required oxygen during prior COVID-19 in comparison to IgG-pts suggesting that infection severity may promote durable immunity. Frequency of early stage cancers was higher among IgG+ pts, suggesting less cancerrelated immunosupression. Older (>70 years) and advanced cancer pts were underrepresented in this series, warranting confirmation of these preliminary results in a larger cohort.

Determinants of enhanced vulnerability to Covid-19 in U.K. cancer patients: Results from the OnCovid study

Background: Despite high contagiousness and rapid spread, SARS-Cov-2 has led to heterogeneous outcomes across affected nations. Within Europe, the United Kingdom is the most severely affected country, with a death toll in excess of 100.000 as of February 2021. We aimed to compare the national impact of Covid19 on the risk of death in UK cancer patients versus those in continental Europe (EU). Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of cancer patients consecutively diagnosed with Covid-19 in 27 centres from February 27 to September 10, 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline, oncological and Covid-19 specific therapy across cohorts and tested these in multivariable Cox regression models to identify predictors of adverse outcome in UK versus EU patients. Results: Compared to EU patients (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001), higher risk of death at 30 days (hazard ratio, HR 1.64 [95%CI 1.36-1.99]) and 6 months after Covid-19 diagnosis (47.64% versus 33.33%, p < 0.0001, HR 1.59 [95%CI 1.33-1.88]). UK patients were more often males, of older age and more co-morbid than EU counterparts (p < 0.01). Receipt of anti-cancer therapy was lower in UK versus EU patients (p < 0.001). Despite equal proportions of complicated Covid-19, rates of intensive care admission and use of mechanical ventilation, UK cancer patients were less likely to receive anti-Covid-19 therapies including corticosteroids, anti-virals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of patient's age, gender, tumour stage and status, number of co-morbidities, Covid-19 severity, receipt of anti-cancer and anti-Covid-19 therapy. Rates of permanent cessation of anti-cancer therapy post Covid-19 were similar in UK versus EU. Conclusions: UK cancer patients have been more severely impacted by the unfolding of the Covid-19 pandemic despite societal risk mitigation factors and rapid deferral of anti-cancer therapy. The increased frailty of UK cancer patients highlights high-risk groups that should be prioritised for anti-SARS-Cov-2 vaccination. Continued evaluation of long-term outcomes is warranted.

Identifying and preventing burnout in young oncologists, an overwhelming challenge in the COVID-19 era: a study of the Spanish Society of Medical Oncology (SEOM).

BACKGROUND: Young oncologists are at particular risk of professional burnout, and this could have a significant impact on their health and care of their patients. The coronavirus disease 2019 (COVID-19) pandemic has forced rapid changes in professionals' jobs and training, with the consequent physical and psychological effects. We aimed to characterize burnout levels and determinants in young oncologists, and the effects of the pandemic on their training and health. METHODS: Two online surveys were conducted among oncology residents and young oncology specialists in Spain. The first addressed professional burnout and its determinants before the COVID-19 pandemic, while the second analyzed the impact of the pandemic on health care organization, training, and physical and psychological health in the same population. RESULTS: In total, 243 respondents completed the first survey, and 263 the second; 25.1% reported significant levels of professional burnout. Burnout was more common among medical oncology residents (28.2%), mainly in their second year of training. It was significantly associated with a poor work-life balance, inadequate vacation time, and the burnout score. Nearly three-quarters of respondents (72%) were reassigned to COVID-19 care and 84.3% of residents missed part of their training rotations. Overall, 17.2% of this population reported that they had contracted COVID-19, 37.3% had scores indicating anxiety, and 30.4% moderate to severe depression. Almost a quarter of young oncologists (23.3%) had doubts about their medical vocation. CONCLUSIONS: Burnout affects a considerable number of young oncologists. The COVID-19 pandemic has had a profound impact on causes of burnout, making it even more necessary to periodically monitor it to define appropriate detection and prevention strategies.