725MO - Phase I trial of the DLL3/CD3 IgG-like T cell engager BI 764532 in patients (pts) with DLL3-positive (+) tumours: Focus on neuroendocrine carcinomas

Background

DLL3 is highly expressed on small-cell lung cancer (SCLC) tumours and neuroendocrine carcinomas (NECs). BI 764532 is a DLL3/CD3 IgG-like T cell engager with potent preclinical activity. NCT04429087 is an ongoing phase I dose-escalation trial of BI 764532 in adults with locally advanced/metastatic DLL3+ (confirmed centrally) SCLC, extrapulmonary (ep) NEC or large cell neuroendocrine lung carcinoma. Here we focus on pts with epNEC.

Methods

BI 764532 was given intravenously in 4 regimens: Regimen A (RA; fixed dose q3w); RB1 (fixed dose qw); RB2 (step-in doses, then fixed dose); RB3 (step-in, followed by target dose). Treatment (Tx) continued until progressive disease, unacceptable toxicity, other withdrawal criteria or maximum Tx duration (36 months). Main objective: maximum tolerated dose (MTD) and/or recommended dose for expansion of BI 764532. Other objectives: safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy based on investigator review (RECIST v1.1).

Results

As of 26 July 2023, 129 pts received ≥1 dose (≥ 0.03 μg/kg) of BI 764532 (RA: n=24; RB1: n=10; RB2: n=79; RB3: n=16). Male: 59%; median age: 60 (range 32–81); ECOG PS 0/1: 28/71%; prior PD1/PD-L1 Tx: 49%; ≥2 prior lines of Tx: 70%. Dose limiting toxicities: 1 pt on RA (Grade [G]3 confusion) and 6 pts on RB2 (G5 immune effector cell-associated neurotoxicity syndrome [ICANS]; G4 cytokine release syndrome [CRS]; G3 CRS; G3 ICANS; G3 nervous system disorder and G2 infusion-related reaction). MTD has not been reached; dose escalation is ongoing. 53 pts with epNEC have been treated (ongoing in 14). TRAEs (any/G≥3): 92/17%. The most common TRAEs (any/G≥3) were: CRS (72/4%); pyrexia (26/0%); dysgeusia (19/0%) and fatigue (17/0%); there were no Tx discontinuations due to TRAEs.

In the efficacy population, there were 46 pts with epNEC (gastrointestinal: n=23; genitourinary: n=16; unknown origin: n=7). ORR/DCR was 22/41%. In pts who received clinically active doses of BI 764532 (n=36), ORR/DCR was 28/47%.

Conclusions

BI 764532 showed clinically manageable tolerability; MTD has not been reached. Promising efficacy was observed in pts with epNEC. The study is ongoing.

Clinical trial identification

NCT04429087.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Lynn Pritchard, of Ashfield MedComms, an Inizio company, and funded by Boehringer Ingelheim.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

V. Gambardella: Financial Interests, Personal, Advisory Board: Boehringer; Financial Interests, Institutional, Other, Research: Research Funding: Bayer, Boehringer, Roche; Financial Interests, Institutional, Other, Institutional: Institutional Funding: Genentech, Merck, Roche, Bayer, Lilly, Novartis, Takeda, AstraZeneca, BM. J. Capdevila Castillon: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono; Financial Interests, Personal, Advisory Board: Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Merck Serono, Esteve, ITM; Financial Interests, Personal, Research Grant: Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications, Eisai, Bayer. Y. Kuboki: Financial Interests, Personal, Advisory Board: Takeda, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical, Bayer, Lilly Japan, Ono Pharmaceutical, Bristol Myers Squibb Japan, Merck Serono; Financial Interests, Institutional, Research Funding: Taiho Pharmaceutical, Takeda, Incyte, Daiichi Sankyo, Ono Pharmaceutical, Boehringer Ingelheim, Amgen, Chugai Pharma, GSK, Astellas Pharma, Genmab, Janssen Oncology, AbbVie, Lilly. O. Alese: Financial Interests, Institutional, Research Grant: Taiho Oncology, Ipsen Pharmaceuticals, GSK, Bristol Myers Squibb, PCI Biotech AS, ASCO, Calithera Biosciences, Inc., SynCore Biotechnology Co. Ltd., Suzhou Transcenta Therapeutics Co., Ltd., Corcept Therapeutics Inc., Hutchison MediPharma, Boehringer Ingelheim, cor Inc., Cue Biopharma, Inc., Merck, Syros Pharmaceuticals Inc., Inhibitex Inc., Arcus Biosciences Inc., ImmunoGen; Financial Interests, Personal, Advisory Role: Ipsen Pharmaceuticals, Aadi Bioscience, Taiho, Pfizer, Seagen Inc., Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: AstraZeneca. D. Morgensztern: Financial Interests, Personal, Advisory Board: AbbVie, Eli Lilly, Arcus, Mirati; Non-Financial Interests, Personal, Principal Investigator: AbbVie, Arcus, Merk, Novartis, Pfizer, Bristol Myers Squibb, Incyte, Surface, Amgen, Genprex, Boehringer Ingelheim, NeoImmunotech, Apollomics; Financial Interests, Personal, Advisory Role: Arcus. C.M. Sayehli: Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Eli Lilly, Boehringer Ingelheim, Catalym. M.F. Sanmamed: Non-Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, BMS, Roche; Non-Financial Interests, Personal, Advisory Board: Numab, BMS; Non-Financial Interests, Institutional, Research Grant: Roche, BMS. E. Arriola: Financial Interests, Personal, Other, Honoraria: Takeda, Lilly, Roche, MSD, Boehringer, BMS, AstraZeneca; Financial Interests, Personal, Advisory Role: Takeda, Lilly, Roche, MSD, Boehringer, BMS, AstraZeneca; Financial Interests, Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Takeda, Roche, MSD, AstraZeneca. Z. Oum' Hamed, E. Song, M. Studeny: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. M. Wermke: Financial Interests, Personal, Other, Honoraria: Lilly, Boehringer Ingelheim, Synlab, Janssen, Merck Serono, GWT, Amgen, Novartis; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Novartis, Lilly, Boehringer Ingelheim, ISA Pharmaceuticals, Amgen, Immatics, Bayer, ImCheck Therapeutics; Financial Interests, Institutional, Research Funding: Roche; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Pfizer, Bristol Myers Squibb, AstraZeneca, Amgen, GEMoaB, Sanofi/Aventis, Immatics, Merck Serono.