Abstract 532P
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, Personal, 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: AstraZeneca; 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.