The FDA has placed a partial clinical hold on BioNTech and OncoC4's Phase III PRESERVE-003 trial evaluating gotistobart in patients with metastatic non-small cell lung cancer (NSCLC) who have progressed on anti-PD-(L)1 therapy. The decision follows the observation of varying outcomes between squamous and non-squamous NSCLC patient populations. Both companies have proactively paused new patient enrollment and are working with the FDA to address the concerns.
Details of the Clinical Hold
The partial clinical hold specifically affects the Phase III PRESERVE-003 trial (NCT05671510), which is designed to evaluate gotistobart (BNT316/ONC-392) as a monotherapy versus docetaxel in patients with metastatic NSCLC who have previously progressed after treatment with PD-(L)1 inhibitors. Patients already enrolled in the trial will continue to receive treatment. The companies stated that the hold does not affect other ongoing trials of gotistobart in different cancer types.
Gotistobart: A CTLA-4 Inhibitor
Gotistobart is a next-generation antibody targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), a key regulator of immune responses. The drug is designed to block CTLA-4, potentially enhancing T-cell activity and anti-tumor responses. BioNTech licensed gotistobart from OncoC4 in March 2023, with plans to jointly develop it as a monotherapy and in combination with anti-PD-1 antibodies for solid tumors.
Trial Design and Endpoints
The PRESERVE-003 trial is a randomized study comparing gotistobart to docetaxel in patients with metastatic NSCLC who have progressed on prior PD-1 or PD-L1 inhibitor therapy. According to ClinicalTrials.gov, the trial aimed to enroll 600 participants. The primary endpoint is overall survival (OS) over 36 months. Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and treatment-emergent adverse events.
Broader Implications
The FDA's partial clinical hold highlights the complexities of developing immunotherapies and the importance of understanding differential responses across patient subgroups. While the hold is limited to the PRESERVE-003 trial, it underscores the need for careful monitoring and analysis of clinical trial data to ensure patient safety and optimize treatment strategies. Other trials of gotistobart, including those in ovarian cancer (NCT05446298), prostate cancer (NCT05682443), and advanced solid tumors (NCT04140526), remain unaffected.
