Abstract 541P
Background
Combining anti-PD-1 antibodies, such as ezabenlimab, with other immunomodulatory or targeted therapies may have synergistic effects. This phase II platform trial is investigating ezabenlimab combined with other agents. Here, we present preliminary data from Module C, assessing ezabenlimab plus BI 836880, a humanised bispecific anti-VEGF/Ang2 nanobody.
Methods
Five cohorts are each recruiting 30 pts: 1) locally advanced/metastatic gastric/gastroesophageal adenocarcinoma with ≥1 prior treatment (anti-PD-[L]1 naïve); 2) any advanced/metastatic solid tumours (except non-squamous NSCLC or melanoma) with prior anti-PD-(L)1 treatment, which progressed following at least stable disease (SD) for ≥4 months; 3) advanced/metastatic solid tumours with no benefit from prior anti-PD-(L)1 treatment (SD or progressive disease [PD] in <4 months); 4) locally advanced/metastatic MSS CRC with ≥1 prior treatment (anti-PD-[L]1 naïve); 5) advanced MSS/mismatch repair-proficient endometrial carcinoma, which progressed after 1 line of chemotherapy (anti-PD-[L]1 naïve). Pts will receive BI 836880 720 mg + ezabenlimab 240 mg IV q3w. The primary endpoint is investigator-assessed objective response.
Results
As of Apr 2021, 60 pts have been treated (Cohorts 1/2/3/4/5: 6/12/10/29/3 pts); median treatment duration was 70 [range 12 –160] days. 37 (62%) were male and median age was 62 yrs. 46 (77%) pts experienced any-cause AEs, most commonly (all/G3, %) nausea (27/2) and fatigue (23/2). Two G5 AEs were reported: non-related aspiration pneumonia and cardiac arrest. Drug-related AEs were experienced by 28 (47%) pts, most commonly nausea (20%). Serious and immune-related AEs were reported by 12 (20%) and 4 (7%) pts, respectively. 5 pts had infusion-related reactions (G1, n=2, G2, n=3) and 2 pts had an AE that led to treatment discontinuation (G2 pain and G3 bile duct stone). Of 33 pts evaluable for response, 1 had confirmed partial response (Cohort 5), 21 had SD (Cohorts 2/3/4: 5/1/15 pts).
Conclusions
Ezabenlimab plus BI 836880 had a manageable safety profile and showed preliminary anti-tumour activity. Updated data will be presented.
Clinical trial identification
NCT03697304.
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
M. Hussein: Financial Interests, Personal, Other, Consulting or advisory role: IntegraConnect. E. Arrowsmith: Financial Interests, Personal, Full or part-time Employment: Tennessee Oncology; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Flatiron Health; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: OneOncology; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Sarah Cannon Research Institute; Financial Interests, Personal, Other: Sarah Cannon Research Institute; Financial Interests, Personal, Stocks/Shares: OneOncology; Financial Interests, Institutional, Other, Research funding: AstraZeneca; Financial Interests, Institutional, Other, Research funding: Boehringer Ingelheim; Financial Interests, Institutional, Other, Research funding: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Research funding: Calistoga Pharmaceuticals; Financial Interests, Institutional, Other, Research funding: Celgene; Financial Interests, Institutional, Other, Research funding: Cephalon; Financial Interests, Institutional, Other, Research funding: Chorus; Financial Interests, Institutional, Other, Research funding: Cougar Biotechnology; Financial Interests, Institutional, Other, Research funding: Eisai; Financial Interests, Institutional, Other, Research funding: EMD Serono; Financial Interests, Institutional, Other, Research funding: Evelo Biosciences; Financial Interests, Institutional, Other, Research funding: Exelixis; Financial Interests, Institutional, Other, Research funding: Genentech; Financial Interests, Institutional, Other, Research funding: Gilead Sciences; Financial Interests, Institutional, Other, Research funding: Incyte; Financial Interests, Institutional, Other, Research funding: Merck; Financial Interests, Institutional, Other, Research funding: Millennium; Financial Interests, Institutional, Other, Research funding: Modra Pharmaceuticals; Financial Interests, Institutional, Other, Research funding: Novartis; Financial Interests, Institutional, Other, Research funding: Oncogenex; Financial Interests, Institutional, Other, Research funding: Onyx; Financial Interests, Institutional, Other, Research funding: Peloton Therapeutics; Financial Interests, Institutional, Other, Research funding: Pfizer; Financial Interests, Institutional, Other, Research funding: Sarah Cannon Research Institute; Financial Interests, Institutional, Other, Research funding: Takeda; Financial Interests, Institutional, Other, Research funding: Clovis Oncology; Financial Interests, Institutional, Other, Research funding: Lilly; Financial Interests, Institutional, Other, Research funding: Infinity Pharmaceuticals; Financial Interests, Institutional, Other, Research funding: Janssen Research & Development. H. Arkenau: Financial Interests, Personal, Full or part-time Employment: Hospital Corporation of America; Financial Interests, Personal, Other, Consulting or advisory role: iOncologi; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Guardant Health; Financial Interests, Personal, Other, Honoraria: Bicycle Therapeutics; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Other, Honoraria: Merck KGaA; Financial Interests, Personal, Other, Honoraria: BeiGene; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Research funding: Sarah Cannon Research Institute. Q. Chu: Financial Interests, Personal, Other, Consulting or advisory role: Novartis; Financial Interests, Personal, Other, Consulting or advisory role: Bristol-Myers Squibb; Financial Interests, Personal, Other, Consulting or advisory role: Merck; Financial Interests, Personal, Other, Consulting or advisory role: Lilly; Financial Interests, Personal, Other, Consulting or advisory role: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting or advisory role: Pfizer; Financial Interests, Personal, Other, Consulting or advisory role: AstraZeneca; Financial Interests, Personal, Other, Consulting or advisory role: Eisai; Financial Interests, Personal, Other, Consulting or advisory role: Abbvie; Financial Interests, Personal, Other, Consulting or advisory role: Takeda; Financial Interests, Personal, Other, Consulting or advisory role: Roche; Financial Interests, Personal, Other, Consulting or advisory role: Amgen; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Abbvie; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Research funding: Boehringer Ingelheim; Financial Interests, Personal, Other, Research funding: AstraZeneca. A.R. Hansen: Financial Interests, Personal, Other, Consulting or advisory role: Merck; Financial Interests, Personal, Other, Consulting or advisory role: GlaxoSmithKline; Financial Interests, Personal, Other, Consulting or advisory role: Bristol-Myers Squibb; Financial Interests, Personal, Other, Consulting or advisory role: Eisai; Financial Interests, Institutional, Other, Research funding: Karyopharm Therapeutics; Financial Interests, Institutional, Other, Research funding: Merck; Financial Interests, Institutional, Other, Research funding: Bristol-Myers Squibb; Financial Interests, Personal, Other, Research funding: Boehringer Ingelheim; Financial Interests, Institutional, Other, Research funding: GlaxoSmithKline; Financial Interests, Institutional, Other, Research funding: Roche/Genentech; Financial Interests, Institutional, Other, Research funding: Janssen; Financial Interests, Institutional, Other, Research funding: AstraZeneca/MedImmune; Financial Interests, Institutional, Other, Research funding: Astellas Pharma; Financial Interests, Institutional, Other, Research funding: Macrogenics. D. Erzen: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. S. Qiu: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. A. Lucarelli: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. S. Ulahannan: Financial Interests, Personal, Other, Consulting or advisory role: Bayer; Financial Interests, Personal, Other, Consulting or advisory role: Exelixis; Financial Interests, Personal, Other, Consulting or advisory role: Incyte; Financial Interests, Personal, Other, Consulting or advisory role: Array BioPharma; Financial Interests, Personal, Other, Consulting or advisory role: Eisai; Financial Interests, Personal, Other, Consulting or advisory role: Syros Pharmaceuticals; Financial Interests, Institutional, Other, Research funding and Principal investigator: Regeneron; Financial Interests, Institutional, Other, Research funding and Principal investigator: OncoMed; Financial Interests, Institutional, Other, Research funding and Principal investigator: Incyte; Financial Interests, Institutional, Other, Research funding and Principal investigator: CicloMed; Financial Interests, Institutional, Other, Research funding and Principal investigator: Mersana; Financial Interests, Institutional, Other, Research funding and Principal investigator: Astex Pharmaceuticals; Financial Interests, Institutional, Other, Research funding and Principal investigator: Abbvie; Financial Interests, Institutional, Other, Research funding and Principal investigator: Takeda; Financial Interests, Institutional, Other, Research funding and Principal investigator: Celgene; Financial Interests, Institutional, Other, Research funding and Principal investigator: Merck; Financial Interests, Institutional, Other, Research funding and Principal investigator: Pfizer; Financial Interests, Institutional, Other, Research funding and Principal investigator: G1 Therapeutics; Financial Interests, Institutional, Other, Research funding and Principal investigator: AstraZeneca; Financial Interests, Institutional, Other, Research funding and Principal investigator: Revolution Medicines; Financial Interests, Institutional, Other, Research funding and Principal investigator: Boehringer Ingelheim; Financial Interests, Institutional, Other, Research funding and Principal investigator: ArQule; Financial Interests, Institutional, Other, Research funding and Principal investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Research funding and Principal investigator: Klus Pharma; Financial Interests, Institutional, Other, Research funding and Principal investigator: Tesaro; Financial Interests, Institutional, Other, Research funding and Principal investigator: Macrogenics; Financial Interests, Institutional, Other, Research funding and Principal investigator: evelo biosciences; Financial Interests, Institutional, Other, Research funding and Principal investigator: Tarveda Therapeutics; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Exelixis; Financial Interests, Institutional, Principal Investigator: Incyte; Financial Interests, Institutional, Principal Investigator: Array BioPharma; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Principal Investigator: Syros Pharmaceuticals. All other authors have declared no conflicts of interest.