BI 764532 Earns FDA FTD in Large Cell Lung Neuroendocrine Carcinoma

BI 764532 previously earned fast track designation from the FDA as a treatment for those with previously treated ES-SCLC and patients with advanced or metastatic extrapulmonary NEC that has progressed following at least 1 line of treatment including platinum-based chemotherapy in October 2023.

The FDA has granted fast track designation to BI 764532 as a treatment for patients with DLL3-expressing advanced or metastatic large cell neuroendocrine carcinoma (NEC) of the lung that has progressed on 1 or more previous lines of therapy including platinum-based chemotherapy, according to a press release from Oxford BioTherapeutics.¹

“We are delighted about the clinical development to help address unmet needs for people living with small cell lung cancer [SCLC] and other [NEC],” Christian Rohlff, chief executive officer at Oxford BioTherapeutics, said in the press release. “This is an important milestone for our teams and exciting news for the community.”

The investigational DLL3/CD3 IgG-like T-cell engager is currently being assessed as a therapy for patients with relapsed or refractory extensive-stage SCLC (ES-SCLC) and those with other relapsed/refractory NEC in the phase 2 DAREON-5 study (NCT05882058). Investigators announced that the first patient received a dose of study treatment in October 2023.²

In the open-label, multi-center, dose-selection DAREON-5 study, patients will be randomly assigned to receive BI 764532 at one of 2 dosing levels. The trial’s primary end points are objective response rate based on RECIST v1.1 criteria and treatment-emergent adverse effects (TEAEs). Secondary end points include duration of response, progression-free survival, disease control rate, overall survival, and TEAEs leading to treatment discontinuation.

Patients 18 years and older with histologically or cytologically confirmed SCLC; extrapulmonary NEC, medullary thyroid cancer, and neuroendocrine prostate cancer; or large cell NEC of the lung with a prominent NEC or small tumor cell component were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1, measurable lesions per RECIST v1.1 guidelines, availability of tumor tissue sample, and adequate organ function.

Patients with untreated or symptomatic brain metastases or presence of leptomeningeal disease were unable to enroll on the trial. Other exclusion criteria included active or prior interstitial lung disease, prior treatment with DLL3-targeting agents, and unresolved toxicity from previous anti-cancer therapies.

BI 764532 previously earned fast track designation from the FDA as a treatment for those with previously treated ES-SCLC and patients with advanced or metastatic extrapulmonary NEC that has progressed following at least 1 line of treatment including platinum-based chemotherapy in October 2023.³

“We are delighted about the accelerated clinical development of BI 764532, for which the DLL3 antigen was discovered using our OGAP® technology platform,” Rohlff said in a press release at the time of the previous fast track designation.³ “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.”

References

1. Oxford BioTherapeutics announces partner Boehringer Ingelheim received U.S. FDA fast track designation for BI 764532 for the potential treatment of advanced or metastatic large-cell neuroendocrine carcinoma of the lung. News release. Oxford BioTherapeutics. November 29, 2023. Accessed November 29, 2023. https://bit.ly/4a1sQIr
2. Oxford BioTherapeutics announces partner Boehringer Ingelheim dosed first patient in phase 2 trial with BI 764532 in small cell lung cancer and other neuroendocrine cancers. News release. Oxford BioTherapeutics. October 24, 2023. Accessed November 29, 2023. https://bit.ly/3Taf4NA
3. 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 November 29, 2023. https://yhoo.it/3PIF8fs