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

ABSTRACT

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.