FDA Places Partial Clinical Hold on Phase 3 Gotistobart NSCLC Trial
The agency places a partial clinical hold on the phase 3 PRESERVE-003 trial due to varying results between the squamous and nonsquamous NSCLC cohorts.
Developers designed gotistobart as a next-generation CTLA-4–targeted antibody administered as monotherapy or in combination with other agents for various cancer types. Investigators hypothesized that blocking CTLA-4 may help preserve T-cell activity while boosting anti-tumor activity, and that gotistobart specifically may preserve CTLA-4 recycling and the immunosuppressive T-cell function in peripheral tissues.
The FDA has placed a partial clinical hold on the phase 3 PRESERVE-003 trial (NCT05671510) evaluating gotistobart (BNT316/ONC-392) vs docetaxel in patients with metastatic non–small cell lung cancer (NSCLC), according to a regulatory document published by the United States Securities and Exchange Commission.1
Developers BioNTech and OncoC4 acknowledge that the regulatory agency has placed a partial clinical hold on the PRESERVE-003 trial due to varying results across the nonsquamous and squamous disease cohorts. Additionally, a recent assessment from an independent data monitoring committee identified potential variance in results based on disease histology. Based on this development, developers decided to halt enrollment of additional patients before informing the FDA of potential variance in results to further align with the agency.
Patients who are already enrolled on the PRESERVE-003 trial are eligible to continue receiving study treatment as developers determine the suitable next steps for evaluating gotistobart in NSCLC. The partial clinical hold on PRESERVE-003 does not impact any other trials evaluating gotistobart in other indications.
Developers designed gotistobart as a next-generation CTLA-4–targeted antibody administered as monotherapy or in combination with other agents for various cancer types. Investigators hypothesized that blocking CTLA-4 may help preserve T-cell activity while boosting anti-tumor activity, and that gotistobart specifically may preserve CTLA-4 recycling and the immunosuppressive T-cell function in peripheral tissues. Through this approach, gotistobart may yield fewer immune-related adverse effects and produce a more favorable safety profile during treatment.
Investigators designed PRESERVE-003 as a 2-stage, multicenter phase 3 trial to assess gotistobart among patients with NSCLC who had disease progression on prior treatment with PD-L1 inhibitors.2 In stage 1 of the study, patients were assigned 1:1:1 to receive gotistobart at 3 mg/kg every 3 weeks (n = 40), 10 mg/kg for 2 doses followed by 6 mg/kg every 3 weeks (n = 40), or docetaxel at 75 mg/m2 every 3 weeks (n = 40). In stage 2 of the trial, patients were assigned to receive gotistobart at the selected dose every 3 weeks (n = 240) or docetaxel every 3 weeks (n = 240).
The trial’s primary end point was overall survival. Secondary end points included progression-free survival, objective response rate, duration of response, disease control rate, and best overall response.
Patients 18 years and older with histologically or cytologically confirmed metastatic NSCLC and radiographic progression on prior therapy with a PD-1 or PD-L1 inhibitor were eligible for enrollment on the trial. Other eligibility criteria included having 1 or more measurable lesions based on RECIST v1.1 guidelines, an ECOG performance status of 0 or 1, adequate organ function, and a minimum life expectancy of 3 months.
Those with treatment-related toxicities that have not resolved to grade 1 or lower apart from endocrinopathy or systemic steroid therapy within a week of beginning study treatment were ineligible for enrollment. Patients were also unsuitable for enrollment if they had documented mutations or alterations in EGFR, ALK, ROS1, HER2, MET, BRAF, RET, or NTRK; symptomatic brain metastases; active gastrointestinal disease; active interstitial lung disease or non-infectious pneumonitis; or impaired heart function.
Developers announced the launch of the phase 3 PRESERVE-003 trial in June 2023.3 At the time of the trial’s initiation, investigators anticipated an approximate enrollment of 600 patients with metastatic NSCLC at sites across the United States, Belgium, Germany, Italy, Spain, and Turkey.
Investigators are currently assessing gotistobart plus pembrolizumab (Keytruda) in platinum-resistant ovarian cancer as part of a phase 2 trial (NCT05446298). The agent is also under evaluation for patients with metastatic castration-resistant prostate cancer in a phase 1/2 trial (NCT05682443) and in multiple solid tumors in a phase 1/2 trial (NCT04140526).
References
- United States Securities and Exchange Commission. Form 6-K. BioNTech SE. Published October 18, 2024. Accessed October 18, 2024. https://tinyurl.com/cs8x6nv6
- Socinski MA, He K, Li T, et al. PRESERVE-003: phase 3, two-stage, randomized study of ONC-392 versus docetaxel in metastatic non-small cell lung cancers that progressed on PD-1/PD-L1 inhibitors. J Clin Oncol. 2023;41(suppl 16):TPS9146. doi:10.1200/JCO.2023.41.16_suppl.TPS9146
- BioNTech and OncoC4 initiate pivotal phase 3 trial of BNT316/ONC-392 program in metastatic NSCLC. News release. BioNTech SE and OncoC4, Inc. June 29, 2023. Accessed October 18, 2024. https://tinyurl.com/bake93b9
