BI 764532

Shows activity

Also known as:

Obrixtamig

Cancer types include:

non-small cell lung cancer small cell lung cancer

TrialFetch AI Analysis

Show TrialFetch AI Analysis

Overview

Obrixtamig (BI 764532) is an investigational IgG‑like, DLL3×CD3 T‑cell–engaging bispecific antibody being developed for DLL3‑positive small cell lung cancer (SCLC) and other high‑grade neuroendocrine carcinomas (NECs). Early clinical studies report antitumor activity with a predominantly cytokine‑release‑syndrome (CRS)–centric safety profile. Multiple phase 1/2 studies are ongoing, including monotherapy, first‑line combinations, and combination with single‑agent chemotherapy. (ascopubs.org)

Mechanism of action

DLL3 is aberrantly expressed on many SCLC and poorly differentiated NECs but with minimal expression in normal adult tissues. Obrixtamig binds DLL3 on tumor cells and CD3 on T cells, forming an immunologic synapse that redirects T‑cell cytotoxicity against DLL3‑expressing cells. Preclinical work showed selective killing of DLL3‑positive cells and tumor regression in human T‑cell–engrafted models. (aacrjournals.org)

Efficacy

Phase 1 (NCT04429087) – dose escalation/optimization in DLL3‑positive SCLC and NECs:
In an SCLC‑focused analysis, among patients receiving at least the target (active) dose, ORR was 33% (all partial responses) and disease control rate (DCR) 66% in heavily pretreated SCLC. (jto.org)
Meeting reports from ASCO 2023 indicated, at doses ≥90 μg/kg, ORR was 26% in SCLC (n=39), 19% in extrapulmonary NECs (epNEC; n=27), and 60% in large‑cell NEC (LCNEC; n=5); overall ORR 25% and DCR 52%, with median duration of response not reached at data cut‑off. (onclive.com)
ESMO 2023 epNEC cohort: ORR 22% (efficacy population); among patients at clinically active doses, ORR 28% and DCR 47%. (oncologypro.esmo.org)
ESMO 2024 update reported continued activity across SCLC, epNEC, and LCNEC with regimen‑specific response rates; signals of higher response were observed in LCNEC in a small cohort. (Data continue to mature.) (oncologypro.esmo.org)

Note: Response assessments in phase 1 were investigator‑assessed per RECIST v1.1 and reflect heavily pretreated populations. Trials remain ongoing. (ascopubs.org)

Safety

The most frequent treatment‑related adverse event is CRS, typically grade 1–2 and occurring early during treatment; high‑grade CRS has been uncommon. Other common events include pyrexia, asthenia/fatigue, dysgeusia, and decreased lymphocyte counts. Reported phase 1 safety summaries include: - SCLC‑focused analysis: any‑grade CRS 53% (grade ≥3: 2%); other AEs included asthenia (26%/2% grade ≥3), lymphopenia (21%/19%), nausea (17%), pyrexia (17%). Step‑in dosing and standard CRS management (supportive care, corticosteroids, anti‑IL‑6R) were used. (jto.org) - epNEC cohort (ESMO 2023): any‑grade CRS 72% (grade ≥3: 4%); no treatment discontinuations due to treatment‑related AEs were reported in this abstract. (oncologypro.esmo.org)

Across early studies, dose‑limiting toxicities have been infrequent, and the maximum tolerated dose had not been reached at the time of the reported analyses. (jto.org)

Ongoing trials and regulatory status

Monotherapy phase 1 (first‑in‑human): NCT04429087 (recruiting). Objectives include defining MTD/RP2D and characterizing safety/PK/PD and preliminary efficacy. (ascopubs.org)
Phase 2 (DAREON‑5): an open‑label trial in relapsed/refractory ES‑SCLC and other NECs. (aacrjournals.org)
First‑line combination (DAREON‑8): BI 764532 plus platinum/etoposide with anti‑PD‑L1 antibody in extensive‑stage SCLC (phase 1 dose escalation/expansion). (ascopubs.org)
Combination with single‑agent chemotherapy in previously treated ES‑SCLC (DAREON‑9; phase 1). (mayo.edu)

Designations: FDA Fast Track designations have been announced for ES‑SCLC after ≥2 prior lines, epNEC after ≥1 prior line, and LCNEC of the lung; FDA Orphan Drug designation has been announced for SCLC. (Company/partner communications.) (globenewswire.com)

Active trials using BI 764532

Found 3 active trials using this drug:

DAREON™-9: A Phase Ib Open-label Dose Escalation and Dose Confirmation Safety Study of Intravenous BI 764532 in Combination With a Single Agent Chemotherapy for the Treatment of Patients With Relapsed/Refractory Small Cell Lung Cancer After Platinum-based Chemotherapy

Sponsor: Boehringer Ingelheim (industry) Phase: 1 Start date: Feb. 14, 2024

TrialFetch AI summary: Adults with relapsed/refractory extensive-stage SCLC after platinum (and prior PD-1/PD-L1 if given) eligible for single-agent chemotherapy receive IV BI 764532, a DLL3×CD3 bispecific T‑cell engager, combined with chemotherapy (dose escalation) and then with topotecan (dose confirmation). Key exclusions include active/untreated brain mets and prior DLL3-directed T-cell therapies.

ClinicalTrials.gov ID: NCT05990738

DAREON™-5: An Open-label, Multi-center Phase II Dose Selection Trial of Intravenous BI 764532, a DLL3-targeting T Cell Engager, in Patients With Relapsed/Refractory Extensive-stage Small Cell Lung Cancer and in Patients With Other Relapsed/Refractory Neuroendocrine Carcinomas

Sponsor: Boehringer Ingelheim (industry) Phase: 2 Start date: Oct. 13, 2023

TrialFetch AI summary: Adults with relapsed/refractory extensive-stage SCLC (post ≥2 lines including platinum and, where standard, PD‑L1 inhibitor) or other high‑grade neuroendocrine carcinomas (including pulmonary LCNEC and DLL3‑high extrapulmonary NEC after ≥1 platinum) receive intravenous BI 764532, a DLL3/CD3 bispecific T‑cell engager redirecting T‑cell cytotoxicity to DLL3‑expressing tumors. Part 1 randomizes between two dose levels; Part 2 expands at the selected dose in centrally confirmed DLL3‑high extrapulmonary NEC.

ClinicalTrials.gov ID: NCT05882058

A First-In-human Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of BI 764532 Administered by Parenteral Route in Patients With Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3

Sponsor: Boehringer Ingelheim (industry) Phase: 1 Start date: Sept. 23, 2020

TrialFetch AI summary: This trial enrolls adults with advanced, DLL3-positive small cell lung cancer, large cell neuroendocrine lung carcinoma, or neuroendocrine carcinoma of any origin who have progressed after standard therapies, to receive BI 764532—a parenterally administered DLL3/CD3 bispecific T-cell engager antibody. Eligible patients must have good performance status and adequate organ function, and may include those with treated or stable brain metastases.

ClinicalTrials.gov ID: NCT04429087