BioNTech SE has been informed by its partner OncoC4, Inc. that the U.S. Food and Drug Administration has lifted the partial clinical hold on PresERVE-003 (NCT05671510), a two-stage, open-label, randomized Phase 3 trial evaluating the efficacy and safety of BNT316 ONC-392 (gotistobart) as monotherapy in patients with metastatic non-small cell lung cancer (NSCLC) that progressed under previous PD-(L)1-inhibitor treatment. Based on the available trial data and following an alignment with the FDA, the companies will solely continue enrollment of patients with squamous NSCLC. The partial clinical hold on the study was previously announced by BioNTech on October 18, 2024, following OncoC4's communication to the FDA after an assessment of the trial data by the independent Data Monitoring Committee which identified a possible variance in results between the squamous and non-squamous NSCLC patient populations.
The partial clinical hold only affected new patient enrollment and did not impact patients already enrolled in the trial. Trials evaluating BNT316 ONC-393 in other indications also remained unaffected. BNT316 ONC-391 (gotistobart) is a next-generation anti-CTLA-4 antibody candidate jointly being developed by BioNTech and OncoC4.
BNT316 ONc-392 is currently in late-stage clinical development as monotherapy or combination therapy in various cancer indications. The immune checkpoint receptor CTLA-4 inhibits T cell immune response and reduces the activity of T cells in recognizing and eliminating cancer cells. This mechanism is also exploited by cancer cells to prevent them from being eliminated by T cells.
Blocking CTLA-4 may help to preserve T cell activity and enhance anti-tumor activity. BNT316 ONC -392 was designed with the aim to address this mechanism while preserving CTLA-4 recycling and thus the immunosuppressive T cell (regulatory T cells, or Tregs") function in the peripheral tissues. This approach aims to give rise to fewer immune-related adverse effects and a more favorable safety profile.
The PresERVE-003 trial (NCT056715 10), which was the subject of the partial clinical hold, is a registrational Phase 3 trial to evaluate the candidate as monotherapy in patients with prostate non-small cell lung cancer. In addition, the candidate is being evaluated in a Phase 2 trial as a combination therapy with pembrolizumab in platinum-resistant ovarian cancer (NCT05446298), in a Phase1 2 trial in metastatic castration-resistant prostate cancer (NCT05682443) as well as in a Phase 1 2 trial in multiple solid tumors (NCT04140526).