75MO - Phase I trial of the DLL3/CD3 IgG-like T cell engager BI 764532 in patients (pts) with DLL3+ tumors: Focus on Asian pts

Background

DLL3 is expressed on small-cell lung cancer (SCLC) tumors and neuroendocrine carcinomas (NECs). NCT04429087 is an ongoing phase I dose-escalation trial of BI 764532, a DLL3/CD3 IgG-like T-cell engager, in pts with locally advanced/metastatic DLL3+ SCLC, extrapulmonary (ep) NEC or large cell NEC of the lung (LCNEC). Here we focus on Asian pts.

Methods

BI 764532 was given iv in 3 regimens: Regimen A (RA; fixed dose q3w); RB1 (fixed dose qw); RB2 (step-in doses followed by a fixed dose). Treatment (Tx) continued until progressive disease, unacceptable toxicity, other withdrawal criteria or max Tx duration (36 mo). Main objective: MTD and/or recommended dose for expansion. Other objectives: safety, tolerability, PK, PD, and preliminary efficacy (RECIST v1.1).

Results

As of 26 March 2023, 107 pts received ≥1 dose (≥ 0.03 μg/kg) of BI 764532 (RA n=24; RB1 n=10; RB2 n=73). 20 pts were Asian (Japanese n=18). Baseline characteristics (all/Asian): male: 57/60%; median age. years (range): 60 (32–79)/65.5 (35–77); ECOG PS 0: 26/60%; ≥2 prior lines of Tx: 68/45%. Tumor type (all/Asian): SCLC 53/5%, epNEC 38/95%, LCNEC 8/0%. Overall DLTs: 1 pt on RA (G3 confusion) and 4 pts on RB2 (G4 cytokine release syndrome [CRS]; G3 CRS; G3 nervous system disorder and G2 infusion-related reaction). MTD has not been reached. Dose escalation is ongoing. One DLT occurred in an Asian pt (G3 CRS). TRAEs were similar in all pts and Asian pts (Table). Tx discontinuations due to TRAEs (all/Asian): 4/0%. Overall, ORR in pts who received clinically active doses of BI 764532 (n=71) was 25% (SCLC 26%; epNEC 19%; LCNEC 60%). In Asian pts who received clinically active doses (n=13), ORR was 23%. As of 21 April 2023, all 3 responding Asian pts were ongoing Tx (duration: 392, 121, 35 days). Table: 75MO

*Efficacy population: ≥1 post-baseline tumor assessment (P-BTA) or permanently discontinued before first P-BTA; responses evaluated per RECIST v1.1 criteria; ^†Discontinued before first P-BTATRAEs occurring in ≥15% of pts are listed

Conclusions

BI 764532 showed manageable tolerability; MTD has not been reached. Promising efficacy was observed in SCLC, epNEC and LCNEC. The tolerability and efficacy of BI 764532 was similar in Asian pts and the overall population.

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.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

Y. Kuboki: Financial Interests, Personal, Speaker, Consultant, Advisor: 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.B. 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., Corcept Therapeutics Inc., Hutchison MediPharma, Boehringer Ingelheim, Xencor Inc., Cue Biopharma, Inc., Merck, Syros Pharmaceuticals Inc., Inhibitex Inc, Arcus Biosciences Inc.; Financial Interests, Personal, Research Grant: ImmunoGen; Financial Interests, Personal, Advisory Board: Ipsen Pharmaceuticals, Aadi Bioscience, Taiho, Pfizer, Seagen Inc., Bristol Myers Squibb, AstraZeneca. D. Morgensztern: Financial Interests, Personal, Advisory Board: AbbVie, Eli Lilly, Arcus, Mirati; Non-Financial Interests, Personal, Principal Investigator: AbbVie, Arcus, Merk, Novartis, Bristo-Myers Squibbb, Incyte, Surface, Amgen, Genprex, Boehringer Ingelheim, NeoImmunotech, Apollomics 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: Financial Interests, Personal, Other, Honoraria: BMS, MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: Numab; Financial Interests, Personal, Research Grant: Roche. E. Arriola: Financial Interests, Personal, Other, Honoraria: Takeda, Lilly, Roche, MSD, Boehringer Ingelheim, BMS, AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: Takeda, Lilly, Roche, MSD, Boehringer Ingelheim, BMS, AstraZeneca; Financial Interests, Personal, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Travel, Accomodation, Exspense: Takeda; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Roche, MSD, AstraZeneca. J. Wolf: Financial Interests, Personal, Other, Honoraria: AbbVie, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, MSD, Novartis, Roche, Amgen, Bayer, Blueprint Medicines, Chugai Pharma Europe, Daiichi Sankyo Europe GmbH, Ignyta, Janssen, Lilly, Loxo, Loxo/Lilly, Pfizer, Seattle Genetics, Takeda, Nuvalent, Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor: AbbVie, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharma, Ignyta, Lilly, MSD Oncology, Novartis, Pfizer, Roche, Janssen, Loxo/Lilly, Blueprint Medicines, Amgen, Takeda, Bayer, Daiichi Sankyo Europe GmbH, Seattle Genetics, Nuvalent, Inc; Financial Interests, Personal, Research Funding: Bristol Myers Squibb, Novartis, Pfizer, Janssen. T.K. Owonikoko: Financial Interests, Personal, Research Funding: Novartis, Bayer, Regeneron, AstraZeneca, G1 Therapeutics, Bristol-Myers, United Therapeutics, Amgen, Loxo/Lilly, Fujifilm, Pfizer, Aeglea Biotherapeutics, Incyte, Merck, Mersana, Turning Point, Oncorus, Ipsen, Eisai, Roche/Genentech, Cardiff Oncology, Ym; Financial Interests, Personal, Advisory Board: Novartis, Lilly, AbbVie, Eisai, G1 Therapeutics, Bristol Myers Squibb, Lilly, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, XCovery, Bayer, Merck, Oncocyte, Takeda, Bayer, Jazz, Zentalis, Ipsen, Daichi, Janssen, BeiGene, Genentech, E; Financial Interests, Personal, Other, IRC/DSMB: EMD Serono; Roche/Genentech, Takeda. M. Studeny: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. M. Bouzaggou: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. E. Song: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. M. Wermke: Financial Interests, Personal, Other, Honoraria: Lilly, Boehringer Ingelheim, SYNLAB, Jannsen, Merck Serono, GWT, Amgen, Novartis; Financial Interests, Personal, Advisory Role: Bristo-Myers Squibbb, 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, Amgen, Sanofi/Aventis, immatics, Merck Serono. All other authors have declared no conflicts of interest.