670P - Phase I trial of the delta-like ligand-3 (DLL3)/CD3 IgG-Like T cell engager BI 764532 in patients (pts) with DLL3-positive tumors: Updated data

Background

DLL3 is expressed on many cancers, including small-cell lung cancer (SCLC), extrapulmonary neuroendocrine carcinomas (epNECs), and large cell neuroendocrine carcinoma of the lung (LCNEC). BI 764532 is a DLL3/CD3 IgG-like T cell engager that initiates T cell-mediated immune responses against DLL3+ tumors. NCT04429087 is a Phase I trial of BI 764532 in pts with DLL3+ SCLC, epNECs or LCNEC.

Methods

Escalating doses of BI 764532 were given IV in 4 regimens: RA (fixed dose q3w); RB1 (fixed dose qw); RB2 and RB3 (step-in dose, then target dose). Treatment (Tx) continued until progression, unacceptable toxicity, other withdrawal criteria, or for 36 months (mos) maximum. Primary objective: determine MTD and/or RDE of BI 764532. Other objectives: safety; tolerability; PK/PD; preliminary efficacy (investigator-assessed; RECIST 1.1).

Results

As of Feb 21, 2024, 168 pts had ≥1 dose of BI 764532 (RA: n=24; RB1: n=10; RB2: n=79; RB3: n=55). Median age: 61 yrs (range 32–81); ECOG PS 0/1/missing: 27/67/5%; prior PD1/PD-L1 Tx: 51%; ≥2 prior lines of Tx: 72%. SCLC/epNEC/LCNEC: 49/42/8%. 6 pts experienced DLTs during the MTD evaluation period (all on RB2): G4 CRS; G3 CRS; G5 ICANS; G3 ICANS; G3 nervous system disorder; G2 infusion-related reaction). MTD was not reached. TRAEs (any/G3+): overall 88/24%; RA 79/21%; RB1 60/20%; RB2 96/34%; RB3 86/11%. Most common TRAEs were (any/G3+): CRS (57/3%); dysgeusia (23/0%); pyrexia (21/0%); asthenia (20/1%). With RB2/RB3, most CRS and neurological events occurred early, and were reversible. Unconfirmed tumor response data are shown below. Efficacy was highest with RB2/RB3 where all pts received target doses of ≥90 μg/kg. Overall, median DoR (95% CI): 8.5 mos (6.2—NR); estimated 6-mo DoR: 70%. 23/38 responding pts are still on Tx. Median PFS (95% CI): 1.5 mos (1.4-2.4); estimated 6-mo PFS: 20%.

Conclusions

BI 764532 showed clinically manageable tolerability and promising efficacy in SCLC, epNEC and LCNEC. Table: 670P

*Assessable pts started Tx ≥7 wks prior to data cut-off; †tumor type missing in one patient

Clinical trial identification

NCT04429087.

Editorial acknowledgement

Medical writing support for the development of this abstract was provided by Lynn Pritchard, DPhil, of Ashfield MedComms.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

M. Wermke: Financial Interests, Personal, Other, Honoraria: Amgen, Boehringer Ingelheim, Eli Lilly, GWT, Janssen, Merck Serono, Novartis, Synlab; Financial Interests, Personal, Other, Travel/accommodation/expenses: Amgen, AstraZeneca, Bristol Myers Squibb, GEMoaB, Immatics, Merck Serono, Pfizer, Sanofi/Aventis; Financial Interests, Personal and Institutional, Research Funding: Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, ImCheck Therapeutics, Immatics, ISA Pharmaceuticals, Novartis. V. Gambardella: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Genentech, Merck Serono, Roche, Beigen, Bayer, Servier, Lilly, Novartis, Takeda, Astelas, Fibrogen, Amcure, Natera, Sierra Oncology, AstraZeneca, Medimmune, BMS, MSD; Financial Interests, Personal, Research Funding: Bayer, Boehringer Ingelheim, Roche. Y. Kuboki: Financial Interests, Personal, Advisory Board: Amgen, Boehringer Ingelheim, Takeda, Incyte, Abbie; Financial Interests, Personal, Other, Honoraria: Eli Lilly Japan, Taiho Pharmaceutical, Takeda; Financial Interests, Institutional, Research Funding: AbbVie, Amgen, Astellas Pharma, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, Eli Lilly, Genmab, Incyte, Ono Pharmaceutical, Taiho Pharmaceutica, Takeda, AstraZeneca, Merck, Novartis, Hengrui. E. Felip: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Genmab, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, Daiichi Sankyo; Financial Interests, Personal, Other, independent member of the board: Grifols; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Peervoice, Pfizer, Sanofi, Takeda, Touch Oncology. M.F. Sanmamed: Non-Financial Interests, Personal and Institutional, Research Funding: Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Numab; Financial Interests, Personal, Royalties: MSD. O. Alese: Financial Interests, Personal, Advisory Board: Ipsen Pharmaceuticals, Aadi Bioscience, Taiho, Pfizer, Seagen Inc., Bristol Myers Squibb, AstraZeneca, Exelixis, Takeda; Financial Interests, Institutional, Research Grant: Taiho Oncology, Ipsen Pharmaceuticals, GSK, Bristol Myers Squibb, Suzhou Transcenta Therapeutics Co. Ltd., Boehringer Ingelheim, Cue Biopharma, Inc., Merck, Inhibitex Inc, Arcus Biosciences Inc. C.M. Sayehli: Financial Interests, Institutional, Coordinating PI: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel/accommodation/expenses: Boehringer Ingelheim, Catalym, Eli Lilly, Ipsen Pharma. E. Arriola Aperribay: Financial Interests, Personal, Other, Honoraria: Takeda, Lilly, Roche, Boehringer Ingelheim, Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Other, Travel/accommodation/expenses: Takeda, Roche, MSD, AstraZeneca; Financial Interests, Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: Takeda, Lilly, Roche, MSD, Boehringer Ingelheim, BMS, AstraZeneca. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, Merck, Mirati, MSD (Merck Sharp & Dohme), Novartis, Nuvalent, Pfizer, Roche, Seattle Genetic, Takeda, Turning Point; Financial Interests, Institutional, Research Funding: BMS, Janssen, Novartis, Pfizer, AstraZeneca. L. Villaruz: Financial Interests, Personal, Advisory Board: Sanofi, Gilead, Johnson and Johnson, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Advisory Role: EMD Serono. M. Studeny, M. Bouzaggou, X. Fang: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. D. Morgensztern: Financial Interests, Personal, Advisory Board: AbbVie, Eli Lilly, Arcus, Mirati; Financial Interests, Personal, Advisory Role: Arcus; Financial Interests, Personal, Principal Investigator: AbbVie, Arcus, Merck, Novartis, Pfizer, Bristol Myers Squibb, Incyte, Surface, Amgen, Genprex, Boehringer Ingelheim, NeoImmunotech, Apollomics.