BioNTech and its partner OncoC4 have announced that the FDA has lifted the partial clinical hold on the Phase 3 PresERVE-003 trial (NCT05671510) for BNT316 ONC-392 (gotistobart). The trial evaluates the efficacy and safety of BNT316 as a monotherapy in patients with metastatic non-small cell lung cancer (NSCLC) that has progressed following prior PD-(L)1 inhibitor treatment. Based on trial data and alignment with the FDA, enrollment will continue exclusively for patients with squamous NSCLC.
The partial clinical hold, which was announced on October 18, 2024, followed an assessment of trial data by the independent Data Monitoring Committee. The assessment identified a potential variance in results between squamous and non-squamous NSCLC patient populations. The hold only affected new patient enrollment; patients already participating in the trial were not impacted. Trials evaluating BNT316 in other indications were also unaffected.
BNT316: A Next-Generation Anti-CTLA-4 Antibody
BNT316 ONC-392 (gotistobart) is a next-generation anti-CTLA-4 antibody candidate jointly developed by BioNTech and OncoC4. CTLA-4 is an immune checkpoint receptor that inhibits T cell immune response, reducing the ability of T cells to recognize and eliminate cancer cells. Cancer cells exploit this mechanism to evade T cell-mediated destruction.
Blocking CTLA-4 can help preserve T cell activity and enhance anti-tumor activity. BNT316 was designed to address this mechanism while preserving CTLA-4 recycling and the function of immunosuppressive T cells (regulatory T cells, or Tregs) in peripheral tissues. This approach aims to reduce immune-related adverse effects and improve the safety profile.
Ongoing Clinical Development
Beyond the PresERVE-003 trial in squamous NSCLC, BNT316 is in late-stage clinical development as a monotherapy or combination therapy across various cancer indications. This includes a Phase 2 trial in combination with pembrolizumab for platinum-resistant ovarian cancer (NCT05446298), a Phase 1/2 trial in metastatic castration-resistant prostate cancer (NCT05682443), and a Phase 1/2 trial in multiple solid tumors (NCT04140526).
