1061P Safety of cemiplimab for advanced cutaneous squamous cell carcinoma: The Spanish named patient programme

Background: Cemiplimab is a programmed cell death receptor-1 inhibitor with antitumour activity for cutaneous squamous cell carcinoma (CSCC) and acceptable safety proved in its pivotal trial. We provide the first data on cemiplimab safety in daily practice from the named patient programme (NPP) for advanced CSCC in Spain. Methods: This cemiplimab NPP was performed from March 2019 to March 2020. It included patients aged ≥18 years with advanced CSCC and ineligible for surgery, radiation therapy or clinical trials. The cemiplimab safety was assessed according to treatment-emergent adverse events (TEAEs) reported until March 2021. Results: 140 patients were included (median age [interquartile range, IQR] 77.0 [65.0-84.0] years;age ≥80 38%;men 71.7%;≥1 comorbidity 83%;ECOG 0-1 86.3%;locally advanced CSCC 60.7%;cemiplimab as first-line therapy 67.7%). Cemiplimab was received for a median (IQR) of 8.0 (3.0-14.0) cycles. Fifty-eight (41.4%) patients showed ≥1 of the 163 TEAEs reported, which most frequently included diarrhoea n=7, asthenia n=6, constipation n=4 and abdominal pain n=4. Fourteen (8.6%) were immune-mediated, mainly bronchitis n=2, pneumonitis n=2 and hepatitis n=2. Seventy-eight (47.9%) TEAEs were grade ≥3, most frequently pneumonia n=3, COVID-19 n=3, general physical health deterioration n=2, pyrexia n=2, renal transplant failure n=2, sepsis n=2, acute kidney injury n=2 and respiratory failure n=2. Twenty-one (12.9%) were treatment-related (TREAEs): 11 (6.7%) were grade 1-2 (diarrhoea n=3 and asthenia, hepatotoxicity, malnutrition, odynophagia, polymyalgia rheumatica, pneumonitis, pruritus, and skin toxicity), 9 (5.5%) grade 3 (acute kidney injury, adrenal insufficiency, abdominal pain, blood creatinine increased, dysphagia, haematuria, immune-mediated enterocolitis, panniculitis, surgical wound infection) and 1 (0.6%) unknown grade. Cemiplimab was withdrawn due to TREAEs in only 5 (3.6%) patients. The TEAE outcome was fatal in 29 (17.8%);none related to cemiplimab. Conclusions: This NPP supports the real-life safety of cemiplimab for CSCC, showing an acceptable safety profile consistent with previous reports. Editorial acknowledgement: Editorial assistance was provided by Esther Álvarez-García at Dynamic Science S.L., funded by Sanofi. Legal entity responsible for the study: Sanofi. Funding: Sanofi. Disclosure: E. Muñoz Couselo: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Pierre Fabre;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Other, Honoraria: Amgen;Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb;Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme;Financial Interests, Personal, Other, Honoraria: Novartis;Financial Interests, Personal, Other, Honoraria: Pierre Fabre;Financial Interests, Personal, Other, Honoraria: Roche;Financial Interests, Personal, Principal Investigator: Amgen;Financial Interests, Personal, Principal Investigator: Bristol-Myers Squibb;Financial Interests, Personal, Principal Investigator: GlaxoSmithKline;Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme;Financial Interests, Personal, Principal Investigator: Novartis;Financial Interests, Personal, Principal Investigator: Pierre Fabre;Financial Interests, Personal, Principal Investigator: Roche;Financial Interests, Personal, Principal Investigator: Sanofi. A. Soria: Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: Sanofi Aventis;Financial Interests, Personal, Invited Speaker: Roche Pharma;Financial Interests, Personal, Invited Speaker: Merck Serono;Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme;Financial Interests, Perso al, Invited Speaker: Bristol-Myers Squibb;Financial Interests, Personal, Invited Speaker: Pierre Fabre;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Sanofi Aventis;Financial Interests, Personal, Advisory Board: Roche Pharma;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Board: Pierre Fabre;Financial Interests, Personal, Principal Investigator: Novartis;Financial Interests, Personal, Principal Investigator: Sanofi Aventis;Financial Interests, Personal, Principal Investigator: Roche Pharma;Financial Interests, Personal, Principal Investigator: Merck Serono;Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme;Financial Interests, Personal, Principal Investigator: Bristol-Myers Squibb;Financial Interests, Personal, Principal Investigator: Pierre Fabre. O. Sanmartin: Financial Interests, Personal, Invited Speaker: Sanofi Genzyme;Financial Interests, Personal, Advisory Board: Sanofi Genzyme;Financial Interests, Personal, Officer: Sanofi Genzyme;Financial Interests, Personal, Principal Investigator: Sanofi Genzyme;Financial Interests, Personal, Invited Speaker: Roche Pharma;Financial Interests, Personal, Advisory Board: Roche Pharma;Financial Interests, Personal, Officer: Roche Pharma;Financial Interests, Personal, Principal Investigator: Roche Pharma. J. Cañueto: Financial Interests, Personal, Invited Speaker: Hoffman-La Roche;Financial Interests, Personal, Invited Speaker: Sanofi-Genzyme;Financial Interests, Personal, Invited Speaker: AbbVie;Financial Interests, Personal, Invited Speaker: LeoPharma;Financial Interests, Personal, Other, Consultancy: Sanofi-Genzyme;Financial Interests, Personal, Other, Consultancy: InflaRx;Financial Interests, Personal, Other, Consultancy: Almirall. S. Beá Ardébol: Financial Interests, Personal, Invited Speaker: Meda;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: SunPharma;Financial Interests, Personal, Other, Trial subinvestigator: Sanofi Aventis;Financial Interests, Personal, Other, Trial subinvestigator: SunPharma;Financial Interests, Personal, Other, Trial subinvestigator: PellePharma. R. Fernández-de-Misa Cabrera: Financial Interests, Personal, Advisory Board: Sanofi. A.J. Cunquero-Tomás: Financial Interests, Personal, Invited Speaker: BMS;Financial Interests, Personal, Invited Speaker: Pierre-Fabre;Financial Interests, Personal, Writing Engagements: Sanofi;Financial Interests, Personal, Other, 2021 EADO/WMC Congress inscription fee: Sanofi. L. Fernández Franco: Non-Financial Interests, Personal, Invited Speaker: Merck;Non-Financial Interests, Personal, Invited Speaker: Sanofi;Non-Financial Interests, Personal, Invited Speaker: Servier. I. Romero: Financial Interests, Personal, Invited Speaker: Pharmamar;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: GSK;Financial Interests, Personal, Invited Speaker: Clovis;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Advisory Board: Pharmamar;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: GSK;Financial Interests, Personal, Advisory Board: Clovis;Financial Interests, Personal, Advisory Board: AstraZeneca. J. Medina Martínez: Non-Financial Interests, Personal, Invited Speaker: Roche;Non-Financial Interests, Personal, Speaker’s Bureau: Roche;Non-Financial Interests, Personal, Advisory Board: Roche;Non-Financial Interests, Personal, Invited Speaker: Novartis;Non-Financial Interests, Personal, Speaker’s Bureau: Novartis;Non-Financial Interests, Personal, Advisory Board: Novartis;Non-Financial Interests, Personal, Invited Speaker: BMS;Non-Financial Interests, Personal, Speaker’s Bureau: BMS;Non-Financial Interests, Personal, Ad isory Board: BMS;Non-Financial Interests, Personal, Invited Speaker: MSD;Non-Financial Interests, Personal, Speaker’s Bureau: MSD;Non-Financial Interests, Personal, Invited Speaker: Pierre Fabre;Non-Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre;Non-Financial Interests, Personal, Advisory Board: Pierre Fabre;Non-Financial Interests, Personal, Invited Speaker: Merk;Non-Financial Interests, Personal, Speaker’s Bureau: Merk;Non-Financial Interests, Personal, Invited Speaker: Sanofi;Non-Financial Interests, Personal, Speaker’s Bureau: Sanofi;Non-Financial Interests, Personal, Advisory Board: Sanofi;Non-Financial Interests, Personal, Invited Speaker: Servier. All other authors have declared no conflicts of interest.

REGISTRI: Regorafenib in first-line of KIT/PDGFR wild type advanced GIST: Capatalize the A Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial

Background: Around 15% of adult GIST are wild type for KIT/PDGFRA mutations (KPWT), usually have SDH deficiencies, and are resistant to imatinib (IM). The underlying mechanisms include overexpression of HIF1α in SDH deficient-GIST, high IGFR signaling through MAPK, BRAF mutation or STAT3 activation. Regorafenib (RE), targeting these pathways, could be more active as upfront therapy in KPWT GIST. Methods: Patients (pts) >18, with advanced non pretreated KPWT GIST were eligible after central confirmation by next-generation sequencing (NGS). Eligible pts received RE at 160mg/d for 21/28d cycles. Primary end-point was disease control rate (DCR) at 12 weeks (RECIST 1.1 ) by central radiological assessment (CRA). Secondary objectives were PFS, OS, ORR (RECIST,Choi), safety and QoL. An amendment allowed previous IM (adjuvant). Statistical assumptions [H0 73% and H1 90% (α 0.1 and β 0.2)], defined a sample size of 20 pts. Results: From May 2016 to October 2020, 30pts with KPWT GIST (by Sanger) underwent central molecular screening. Among the 15 non-eligible pts, 8 harbored KIT exon 11 mutations, 3 exon 9 and 3 PDGFRA exon 18 by NGS. The remaining 16 (53.3%) molecularly eligible pts were enrolled and started RE except one pt due to COVID-19 pandemic. The trial was prematurely closed due to low recruitment, especially after COVID outbreak. Demographics and treatment details in the table. Based on CRA, 12w-DCR was 86.7%. With a median (m) FU of 26 (5-44) months (mo), 10/15 pts progressed, with a mPFS of 10.8 mo (95% CI 6.9-14.8). 6 mo, 9 mo and 12 mo PFS rates were 65%, 48% and 29% respectively. 2 pts were PD-free at 25 and 43 mo from start of RE. 6/15 pts died, with a mOS of 33.5 mo (95% CI NR). [Formula presented] Conclusions: The study results approach the prespecified activity threshold. The low recruitment rate could have affected this attainment. Other analysis of secondary endpoints are ongoing. The high percentage of overlooked mutant GIST by Sanger raises the need of NGS in presumed KPWT GIST. Clinical trial identification: NCT02638766. Legal entity responsible for the study: Spanish Group for Research on Sarcoma (GEIS). Funding: Bayer. Disclosure: J. Martin Broto: Financial Interests, Personal, Expert Testimony, Honoraria: Lilly;Financial Interests, Personal, Expert Testimony, Honoraria: PharmaMar;Financial Interests, Personal, Expert Testimony, Honoraria: Eisai;Financial Interests, Personal, Expert Testimony, Honoraria: Bayer;Financial Interests, Personal, Invited Speaker: PharmaMar;Financial Interests, Institutional, Invited Speaker: PharmaMar;Financial Interests, Institutional, Invited Speaker: Eisai;Financial Interests, Institutional, Invited Speaker: Novartis;Financial Interests, Institutional, Invited Speaker: IMMIX Biopharma;Financial Interests, Institutional, Invited Speaker: Lixte;Financial Interests, Institutional, Invited Speaker: Karyopharm;Financial Interests, Institutional, Invited Speaker: Bayer;Financial Interests, Institutional, Invited Speaker: Celgene;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker: BMS;Financial Interests, Institutional, Invited Speaker: Blueprint;Financial Interests, Institutional, Invited Speaker: Deciphera;Financial Interests, Institutional, Invited Speaker: Nektar;Financial Interests, Institutional, Invited Speaker: FORMA;Financial Interests, Institutional, Invited Speaker: Amgen;Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo;Financial Interests, Institutional, Invited Speaker: Lilly;Financial Interests, Institutional, Invited Speaker: AROG;Financial Interests, Institutional, Invited Speaker: Adaptimmune;Financial Interests, Institutional, Invited Speaker: GSK. N. Hindi: Financial Interests, Personal, Invited Speaker: PharmaMar;Financial Interests, Personal, Advisory Board: PharmaMar;Financial Interests, Institutional, Research Grant: PharmaMar;Financial Interests, Institutional, Sponsor/Funding: PharmaMar;Financial Interests, Institutional, Research Grant: Nova tis;Financial Interests, Institutional, Research Grant: Eisai;Financial Interests, Institutional, Research Grant: Immix Bio;Financial Interests, Institutional, Sponsor/Funding: Bayer;Financial Interests, Institutional, Sponsor/Funding: Deciphera;Financial Interests, Institutional, Sponsor/Funding: Daychii;Financial Interests, Institutional, Sponsor/Funding: Blueprint;Financial Interests, Institutional, Sponsor/Funding: Adaptimmune;Financial Interests, Institutional, Sponsor/Funding: GSK;Financial Interests, Institutional, Sponsor/Funding: Karyopharm;Financial Interests, Institutional, Sponsor/Funding: Celgene;Financial Interests, Institutional, Sponsor/Funding: AROG. J. Lavernia: Financial Interests, Personal, Invited Speaker: PharmaMar;Financial Interests, Personal, Invited Speaker: BMS. C. Serrano: Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Institutional, Research Grant: Bayer. D. Moura: Financial Interests, Institutional, Research Grant: Novartis;Financial Interests, Institutional, Research Grant: Eisai;Financial Interests, Institutional, Research Grant: PharmaMar;Financial Interests, Institutional, Research Grant: Immix Bio. J. Blay: Financial Interests, Institutional, Research Grant: Bayer;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Institutional, Research Grant: Novartis;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Institutional, Research Grant: Roche;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Institutional, Research Grant: Deciphera;Financial Interests, Personal, Research Grant: Deciphera. E.R. Fumagalli: Financial Interests, Institutional, Research Grant: Bayer. All other authors have declared no conflicts of interest.