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FDA clamps partial hold on Phase III trial of BioNTech & OncoC4’s NSCLC therapy

A partial clinical hold was placed on the registrational trial after results showed variance between squamous and non-squamous NSCLC patient responses.

The US Food and Drug Administration (FDA) has placed a partial clinical hold on the registrational Phase III PRESERVE-003 trial of BioNTech and OncoC4’s gotistobart.

The study was placed on partial hold after the therapy showed “varying results between the squamous and non-squamous non-small cell lung cancer (NSCLC) patient populations”, as per an SEC filing by BioNTech. The companies have also “proactively” paused the enrolment of new patients and have informed the US regulator “of the possible variance for further alignment.”

The companies were adamant that clinical hold does not affect other gotistobart trials, including a Phase II trial (NCT05446298) in ovarian cancer indication, a Phase I/II trial (NCT05682443) in prostate cancer and a Phase I/II trial (NCT04140526) of gotistobart and MSD’s Keytruda (pembrolizumab) in advanced solid tumours.

Additionally, whilst the companies are not enrolling new patients in the Phase III PRESERVE-003 study, the ones that have already enrolled in the trial will continue to receive treatment. The trial was expected to enrol 600 participants with metastatic NSCLC who have progressed on anti-programmed death ligand 1 (PD1) antibodies, according to ClinicalTrials.gov.

The participants were randomised to receive either gotistobart or a chemotherapy docetaxel. The trial’s primary endpoint is overall survival over 36 months. The study also measures objective response rate, progression free survival and treatment emergent adverse events as part of secondary endpoints.

Gotistobart is an antibody that targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which regulates the body's immune responses. BioNTech licenced the therapy from OncoC4 in March 2023. As part of the agreement, the companies will jointly develop gotistobart in the solid tumour indication both as a monotherapy and in combination with anti-PD1 antibodies. Whilst BioNTech holds sole rights to develop the therapy as a combination, other than with PD-1 inhibitors.

Another anti-CTLA-4 antibody being developed as a treatment for solid tumours is Xilio Therapeutics’ XTX101. It is currently being evaluated as a combination treatment with Roche’s Tecentriq (atezolizumab) in an open-label Phase I/II trial (NCT04896697). The study is co-funded by Roche and Xilio and investigates the combination in advanced solid tumours.