542P - Ezabenlimab (BI 754091) monotherapy in patients (pts) with advanced solid tumours

Background

Ezabenlimab is a PD-1-targeting monoclonal antibody. Ezabenlimab is being investigated as monotherapy and in combination with other anti-cancer agents, and has been administered to >600 pts in combination settings. Here, we report results in pts who received 240 mg ezabenlimab monotherapy every 3 weeks (q3w).

Methods

Data from two phase I dose escalation/expansion trials and a phase I imaging trial are presented. Dose escalation cohorts enrolled pts with any advanced solid tumours. Dose expansion included pts with: select advanced solid tumours (including NSCLC, bladder, melanoma, gastric, ovarian, triple-negative breast cancer and RCC); TMB-high tumours (excluding MSI-high); squamous cell cervical/anal/skin tumours and vaginal or vulvar squamous cell carcinoma. Prior anti-PD-1 therapy was permitted in dose escalation but not in expansion cohorts. Tumour response was evaluated as per RECIST 1.1. Safety was assessed by incidence and severity of adverse events (AEs).

Results

111 pts received ezabenlimab 240 mg q3w. 83 pts (75%) were female; median age, 62 yrs. At data cut-off (Nov 2020), 13 pts remain on treatment. Best overall confirmed response is shown in the table. Duration of response ranged from 43 to 570 days (response was ongoing in 9/16 pts at data cut-off). The most common AEs (all/≥G3) were fatigue (38.7%/3.6%), nausea (28.8%/0) and anaemia (21.6%/10.8%). The most common drug-related AE (all/≥G3) was fatigue (18.0%/0). 33 pts (29.7%) had immune-related AEs, most commonly hypothyroidism (7 pts [6.3%]). 38 pts (34.2%) had serious AEs (2 were considered treatment-related [G2 pyrexia and G3 rash]). There were no AEs leading to death. 2 pts had AEs leading to discontinuation (G2 colitis and G3 musculoskeletal pain). Anti-drug antibodies occurred infrequently and did not affect the PK profile of ezabenlimab.

Conclusions

Ezabenlimab monotherapy showed anti-tumour activity similar to other checkpoint inhibitors and was well tolerated. Table: 542P

Table shows responses in pts with post-baseline assessments; *all pts received ezabenlimab 240 mg q3w; ^†Tumour types: oesophageal, mesothelial; ^‡Tumour types: breast cancer (n=2), fallopian tube, RCC

Clinical trial identification

NCT02952248 (1381.1), NCT03433898 (1381.4), NCT03780725 (1381.3).

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Caroline Allinson, 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.R. Patel: Financial Interests, Personal, Advisory Role: Pharmacyclics/Janssen; Financial Interests, Personal, Advisory Role: Pfizer/EMD Serono; Financial Interests, Personal, Speaker’s Bureau: Exelixis; Financial Interests, Personal, Speaker’s Bureau: Genentech/Roche; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Celgene; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Pharmacyclics; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Janssen Oncology; Financial Interests, Personal, Other, Honoraria: Genentech; Financial Interests, Institutional, Other, Research Funding: Acerta Pharma; Financial Interests, Institutional, Other, Research Funding: ADC Therapeutics; Financial Interests, Institutional, Other, Research Funding: Agenus; Financial Interests, Institutional, Other, Research Funding: Aileron Therapeutics; Financial Interests, Institutional, Other, Research Funding: AstraZeneca; Financial Interests, Institutional, Other, Research Funding: Bicycle Therapeutics; Financial Interests, Institutional, Other, Research Funding: BioNTech AG; Financial Interests, Institutional, Other, Research Funding: Boehringer Ingelheim; Financial Interests, Institutional, Other, Research Funding: Calithera Biosciences; Financial Interests, Institutional, Other, Research Funding: Celgene; Financial Interests, Institutional, Other, Research Funding: Checkpoint Therapeutics; Financial Interests, Institutional, Other, Research Funding: CicloMed; Financial Interests, Institutional, Other, Research Funding: Clovis Oncology; Financial Interests, Institutional, Other, Research Funding: Curis; Financial Interests, Institutional, Other, Research Funding: Cyteir; Financial Interests, Institutional, Other, Research Funding: Daiichi Sankyo; Financial Interests, Institutional, Other, Research Funding: eFFECTOR Therapeutics; Financial Interests, Institutional, Other, Research Funding: Lilly; Financial Interests, Institutional, Other, Research Funding: EMD Serono; Financial Interests, Institutional, Other, Research Funding: Evelo Therapeutics; Financial Interests, Institutional, Other, Research Funding: FORMA Therapeutics; Financial Interests, Institutional, Other, Research Funding: Genentech/Roche; Financial Interests, Institutional, Other, Research Funding: Gilead Sciences; Financial Interests, Institutional, Other, Research Funding: GlaxoSmithKline; Financial Interests, Institutional, Other, Research Funding: H3 Biomedicine; Financial Interests, Institutional, Other, Research Funding: Hengrui Therapeutics; Financial Interests, Institutional, Other, Research Funding: Hutchison MediPharma; Financial Interests, Institutional, Other, Research Funding: Ignyta; Financial Interests, Institutional, Other, Research Funding: Incyte; Financial Interests, Institutional, Other, Research Funding: Jacobio; Financial Interests, Institutional, Other, Research Funding: Janssen; 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M.L. Johnson: Financial Interests, Institutional, Advisory Board: Abbvie; Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Editas Medicine; Financial Interests, Institutional, Advisory Board: Eisai; Financial Interests, Institutional, Advisory Board: G1 Therapeutics; Financial Interests, Institutional, Advisory Board: GlaxoSmithKline; Financial Interests, Institutional, Advisory Board: Ideaya Biosciences; Financial Interests, Institutional, Advisory Board: Incyte; Financial Interests, Institutional, Advisory Board: Ribon Therapeutics; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Principal Investigator: Abbvie; Financial Interests, Institutional, Principal Investigator: Acerta; Financial Interests, Institutional, Principal Investigator: Adaptimmune; Financial Interests, Institutional, Principal Investigator: Amgen; 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I. Winer: Financial Interests, Personal, Advisory Board, Ad Board x1: Merck; Financial Interests, Personal, Research Grant, Investigator Initiated Trial: Oncoceutics. H. Arkenau: Financial Interests, Personal, Full or part-time Employment: Hospital Corporation of America; Financial Interests, Personal, 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. N. Cook: Financial Interests, Personal and Institutional, Advisory Board: RedX Pharmaceuticals; Non-Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Research funding: AstraZeneca; Financial Interests, Institutional, Research Grant, Research funding: Orion; Financial Interests, Institutional, Research Grant, Research funding: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Grant, Research funding: Taiho; Financial Interests, Institutional, Research Grant, Research funding: GSK; Financial Interests, Institutional, Research Grant, Research funding: Novartis; Financial Interests, Institutional, Research Grant, Research funding: Starpharma; Financial Interests, Institutional, Research Grant, Research funding: Bayer; Financial Interests, Institutional, Research Grant, Research funding: Eisai; Financial Interests, Institutional, Research Grant, Research funding: UCB; Financial Interests, Institutional, Research Grant, Research funding: RedX Pharmaceuticals; Financial Interests, Institutional, Research Grant, Research funding: Stemline Therapeutics; Financial Interests, Institutional, Research Grant, Research funding: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, Research funding: Merck; Financial Interests, Institutional, Research Grant, Research funding: Tarveda Therapeutics. R. Aljumaily: Financial Interests, Personal, Advisory Board, Paid advisory board meetings: Regeneron; Financial Interests, Personal, Advisory Board, Paid advisory board meetings: AstraZeneca; Financial Interests, Institutional, Research Grant, Research funding for running the study: Boehringer Ingelheim. S. Kitano: Financial Interests, Personal and Institutional, Principal Investigator: Ono Pharmaceutical Company; Financial Interests, Personal and Institutional, Research Grant: Ono Pharmaceutical Company; Financial Interests, Personal and Institutional, Principal Investigator: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Daiichi-Sankyo; Financial Interests, Personal and Institutional, Principal Investigator: Eisai; Financial Interests, Personal and Institutional, Research Grant: Eisai; Financial Interests, Personal and Institutional, Principal Investigator: Astellas; Financial Interests, Personal and Institutional, Research Grant: Gilead Sciences; Financial Interests, Personal and Institutional, Principal Investigator: REGENERON; Financial Interests, Institutional, Research Grant: Takara Bio Inc.; Financial Interests, Personal and Institutional, Principal Investigator: MSD; Financial Interests, Personal and Institutional, Principal Investigator: Chugai; Financial Interests, Personal and Institutional, Research Grant: Astellas; Financial Interests, Personal and Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: PACT Pharma; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Sumitomo Dainippon Pharma; Financial Interests, Personal, Invited Speaker: AYUMI Pharmaceutical Corporation; Financial Interests, Personal, Advisory Board: Rakuten Medical; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Expert Testimony: PMDA(Pharmaceuticals and Medical Devices Agency); Financial Interests, Personal, Advisory Role: ImmuniT research Inc. C. Duffy: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim Pharmaceuticals. M. Ge: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. M. Elgadi: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. L.L. Siu: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: AstraZeneca/Medimmune; Financial Interests, Personal, Advisory Board: Morphosys; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: GeneSeeq; Financial Interests, Personal, Advisory Board: Loxo; Financial Interests, Personal, Advisory Board: Oncorus; Financial Interests, Personal, Advisory Board: Symphogen; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Voronoi; Financial Interests, Personal, Advisory Board: Treadwell Therapeutics; Financial Interests, Personal, Advisory Board: Arvinas; Financial Interests, Personal, Advisory Board: Tessa; Financial Interests, Personal, Advisory Board: Navire; Financial Interests, Personal, Advisory Board: Relay; Financial Interests, Personal, Advisory Board: Rubius; Financial Interests, Personal, Advisory Board: Janpix; Financial Interests, Personal, Ownership Interest, Co-founder - Spouse: Treadwell Therapeutics; Financial Interests, Personal, Stocks/Shares, Stock owners - Spouse: Agios; Financial Interests, Institutional, Research Grant, Clinical trials support: Novartis; Financial Interests, Institutional, Research Grant, Clinical trials support: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant, Clinical trials support: Pfizer; Financial Interests, Institutional, Research Grant, Clinical trials support: Boerhinger-Ingelheim; Financial Interests, Institutional, Research Grant, Clinical trials support: GlaxoSmithKline; Financial Interests, Institutional, Research Grant, Clinical trials support: Roche/Genentech; Financial Interests, Institutional, Research Grant, Clinical trials support: Karyopharm; Financial Interests, Institutional, Research Grant, Clinical trials support: AstraZeneca/Medimmune; Financial Interests, Institutional, Research Grant, Clinical trials support: Merck; Financial Interests, Institutional, Research Grant, Clinical trials support: Celgene; Financial Interests, Institutional, Research Grant, Clinical trials support: Astellas; Financial Interests, Institutional, Research Grant, Clinical trials support: Bayer; Financial Interests, Institutional, Research Grant, Clinical trials support: Abbvie; Financial Interests, Institutional, Research Grant, Clinical trials support: Amgen; Financial Interests, Institutional, Research Grant, Clinical trials support: Symphogen; Financial Interests, Institutional, Research Grant, Clinical trials support: Intensity Therapeutics; Financial Interests, Institutional, Research Grant, Clinical trials support: Mirati; Financial Interests, Institutional, Research Grant, Clinical trials support: Shattucks; Financial Interests, Institutional, Research Grant, Clinical trials support: Avid. All other authors have declared no conflicts of interest.