BI 764532 Earns FDA FTD in SCLC and Extrapulmonary Neuroendocrine Carcinoma

BI 764532 was evaluated as part of a phase 1 trial (NCT04429087) among patients with DLL3-positive SCLC and NEC. Investigators presented findings from the study at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The FDA has granted fast track designation to the DLL3/CD3 IgG-like T-cell engager BI 764532 as a treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) that has progressed following 2 lines of therapy and for those with advanced or metastatic extrapulmonary neuroendocrine carcinomas (NEC) that has progressed after 1 prior line of therapy including platinum-based chemotherapy, according to a press release from Oxford BioTherapeutics.¹

The investigational T-cell engager was evaluated as part of a phase 1 trial (NCT04429087) among patients with DLL3-positive SCLC and NEC. Investigators presented findings from the study at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

Across the overall population (n = 71), patients treated at a dose of 90 μg/kg or higher experienced an overall response rate (ORR) of 25%.² Additionally, the disease control rate was 52% among all patients. Investigators reported an ORR of 26% in a subset of patients with SCLC (n = 39), 19% among those with extrapulmonary NEC (n = 27), and 60% in patients with large cell NEC (n = 5).

Safety data highlighted 5 dose-limiting toxicities, which included grade 3 or 4 cytokine release syndrome in 2 patients, grade 3 confusional state in 1, grade 2 infusion-related reaction in 1, and grade 3 central nervous system (CNS) disorder in 1. Investigators noted that all dose-limiting toxicities were reversible.

“We are delighted about the accelerated clinical development of BI 764532, for which the DLL3 antigen was discovered using our OGAP® technology platform,” Christian Rohlff, chief executive officer at Oxford BioTherapeutics, said in the press release.¹ “Receiving an ES-SCLC or [extrapulmonary] NEC diagnosis can be life changing and there is an urgent, unmet need for additional targeted immunotherapeutics to ensure that individuals [with] these aggressive cancers get the care they need.”

In the first-in-human, open-label, multi-center phase 1 trial, investigators evaluated the highest possible dose of BI 764532 and the most tolerable treatment schedule for patients with SCLC and NEC that is DLL3 positive.

The study’s primary end points were the maximum-tolerated dose (MTD) and the number of patients with dose-limiting toxicities during the MTD evaluation period. Secondary end points included ORR per RECIST v1.1 criteria and the maximum measured concentration of BI 764532.

Patients with locally advanced or metastatic cancer not amenable to curative therapy including SCLC, large cell NEC, NEC or small cell carcinoma of any other origin, and DLL3-positive tumors were able to enroll on the trial. Additional eligibility criteria included having adequate liver, bone marrow, and renal organ function; an ECOG performance status of 0 or 1; and at least 1 measurable lesion outside of CNS based on modified RECIST v1.1 criteria.

Those who received prior treatment with a T-cell engager or anticoagulant treatment that could not be safely interrupted based on the investigator’s discretion were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had other active malignancies that could interfere with disease prognosis and management or major surgery within 4 weeks of beginning study treatment.

References

1. Oxford BioTherapeutics announces partner Boehringer Ingelheim received U.S. FDA fast track designation for BI 764532 for the treatment of extensive stage small cell lung cancer and extrapulmonary neuroendocrine cancers. News release. Oxford BioTherapeutics. October 3, 2023. Accessed October 3, 2023. https://yhoo.it/3PIF8fs
2. Wermke M, Felip E, Kuboki Y, et al. First-in-human dose-escalation trial of BI 764532, a delta-like ligand 3 (DLL3)/CD3 IgG-like T-cell engager in patients (pts) with DLL3-positive (DLL3+) small-cell lung cancer (SCLC) and neuroendocrine carcinoma (NEC). J Clin Oncol. 2023;41(suppl 16):8502. doi:10.1200/JCO.2023.41.16_suppl.8502