Novel T-cell engager demonstrates activity in neuroendocrine carcinomas
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MADRID — A novel T-cell engager appeared safe and exhibited efficacy as treatment for neuroendocrine tumors, according to study results presented at ESMO Congress.
Delta-like ligand 3 (DLL3) is highly expressed on neuroendocrine carcinomas and small cell lung cancer tumors, according to study background.
BI 764532 (Boehringer Ingelheim) — a DLL3/CD3 T cell-engaging bispecific antibody — has exhibited “potent preclinical activity,” Valentina Gambardella, MD, medical oncologist with INCLIVA Biomedical Research Institute at Hospital Clínico de Valencia in Spain, and colleagues wrote.
An ongoing phase 1 dose-escalation trial is designed to assess the agent for adults with locally advanced or metastatic DLL3-positive extrapulmonary neuroendocrine carcinoma, large cell neuroendocrine lung carcinoma or small cell lung cancer.
Study participants received BI 764532 in one of four IV regimens: a fixed dose every 3 weeks, a fixed dose once weekly, step-in doses followed by fixed dose, or step-in dose followed by target dose.
Treatment continued for 36 months, or until disease progression, unacceptable toxicity or other withdrawal criteria.
Maximum tolerated dose or recommended dose for expansion served as the primary study objective. Additional objectives included safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy per investigator assessment.
As of data cutoff on July 26, 129 patients (median age, 60 years; range, 32-81; 59% men) had received at least one dose ( 0.03 g/kg) of BI 764532 (fixed dose every 3 weeks, n = 24; fixed dose weekly, n = 10; step-in dose/fixed dose, n = 79; step-in dose/target dose, n = 16).
Most study participants had ECOG performance status 0 (28%) or 1 (71%). Half (49%) had received prior PD-1/PD-L1 therapy and most (70%) had received at least two prior lines of therapy.
Seven patients experienced dose-limiting toxicities. One patient who received a fixed dose every 3 weeks developed grade 3 confusion. The other six dose-limiting toxicities occurred among patients who received the step-in dose/fixed-dose regimen. These included one case each of grade 5 immune effector cell-associated neurotoxicity syndrome (ICANS), grade 3 ICANS, grade 4 cytokine release syndrome, grade 3 CRS, grade 3 nervous system disorder and grade 2 infusion-related reaction.
Maximum tolerated dose had not been reached, and dose escalation remained ongoing.
Fifty-three patients with extrapulmonary neuroendocrine carcinoma had been treated and 14 remained on treatment as of data cutoff.
In this group, 92% experienced any treatment-related adverse events, and 17% experienced grade 3 or higher treatment-related adverse events.
The most common treatment-related adverse events included CRS (any grade 72%; grade 3, 4%), pyrexia (any grade, 26%; grade 3, 0%), dysgeusia (any grade, 19%; grade 3, 0%) and fatigue (any grade, 17%; grade 3, 0%).
No patients with extrapulmonary neuroendocrine carcinoma discontinued therapy due to treatment-related adverse events.
An efficacy analysis that included 46 patients with extrapulmonary neuroendocrine carcinoma (gastrointestinal, n = 23; genitourinary, n = 16; unknown origin, n = 7) showed a 22% overall response rate and a 41% disease control rate.
Among the 36 patients who received clinically active doses of BI 764532, researchers reported a 28% ORR and a 47% disease control rate.
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Gambardella V, et al. Abstract 725MO. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.
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