LBA32 - A randomized, phase II, dose optimization of gotistobart, a pH-sensitive anti-CTLA-4, in combination with standard dose pembrolizumab in platinum-resistant recurrent ovarian cancer: Safety, efficacy and dose optimization (PRESERVE-004/GOG-3081)

Background

Gotistobart (ONC-392/BNT316) is a humanized anti-CTLA-4 mAb that preserves CTLA-4 immune checkpoint activity by avoiding lysosomal degradation. The safety and clinical activity of gotistobart monotherapy in ovarian cancer was previously reported [https://doi.org/10.1136/jitc-2022-SITC2022.0564]. We report safety and efficacy results of gotistobart + pembrolizumab in a randomized, open-label, multicenter phase 2 trial in patients with PROC.

Methods

Patients with platinum-resistant high-grade serous OC, tubal or peritoneal cancer who previously received 1 line of platinum-based therapy and progressed between 3-6 months, or received ≥1 line and progressed within 6 months of last dose, were randomized 1:1 to receive different doses of gotistobart + pembrolizumab 200 mg, Q3W. Primary endpoints are ORR (RECIST 1.1) and safety. Secondary endpoints include PFS and OS.

Results

As of May 24, 2024, 83 patients had received ≥1 dose of gotistobart + pembrolizumab with 33 and 29 patients in 1 mg/kg and 2 mg/kg gotistobart + pembrolizumab groups, respectively. At the safety and efficacy cutoff date of May 10, 2024, with a median follow-up of 2.1 months (range 0.1-9.2), grade ≥3 treatment-related adverse events (TRAEs) were observed in 35.7% and 31.0% patients in 1 mg/kg or 2 mg/kg groups, respectively. No grade 5 TRAEs were observed. Common grade 3 TRAEs from combined groups were increased ALT and AST (both 7.0%), and diarrhea (5.3%). Unconfirmed ORR was 31.8% (7/22; 95% CI 13.9-54.9) and 36.4% (8/22; 95% CI 17.2-59.3) in 1 mg/kg and 2 mg/kg groups, respectively. Table: LBA32

*PD included those without post baseline disease assessment

Conclusions

Early results show encouraging safety and clinical activity in PROC patients receiving gotistobart + pembrolizumab.

Clinical trial identification

NCT05446298.

Editorial acknowledgement

Legal entity responsible for the study

OncoC4 Inc, BioNTech SE.

Funding

OncoC4 Inc, BioNTech SE.

Disclosure

J.N. Barlin: Non-Financial Interests, Institutional, Steering Committee Member: FLORA, XPORT; Non-Financial Interests, Institutional, Advisory Board: AstraZeneca, Clovis, Mersana, OncoC4, Immunogen, Eisai; Non-Financial Interests, Institutional, Speaker’s Bureau: AstraZeneca, Merk. P.C. Lim: Non-Financial Interests, Personal, Advisory Board: BioNTech SE, OncoC4. J. Thomes Pepin, E.E. Hopp, N.G. Cloven, C. Lee, H.D. Eshed, D. Black, H.M. Cottrill, L. Hand, D.M. O'Malley, L.T. Chuang, L. Willmott: Non-Financial Interests, Personal, Advisory Board: BioNTech, OncoC4. M. Chisamore: Financial Interests, Institutional, Full or part-time Employment: Merck & Co. Inc; Financial Interests, Institutional, Stocks/Shares: Merck & Co. Inc. S. Shpyro: Financial Interests, Institutional, Full or part-time Employment: BioNTech. J. Durbin, P. Zheng, Y. Liu: Financial Interests, Institutional, Full or part-time Employment: OncoC4. B.J. Monk: Financial Interests, Personal, Other, Consultant: Agenus, Elevar, GOG Foundation, Genmab/Seattle Genetics, Gradalis, Immunogen, Karyopharm, Mersana, Novocure, Pfizer, Acrivon, Alkemers, Amgen, Bayer, BioNtech, Corcept, Duality, EMD Merck, Genalux, Laekna, Novartis, OncoC4, Panavance, Profound Bio, Sarah Cannon Research Institue, Tubulis; Financial Interests, Personal, Other, Consultant/Speaker: AstraZeneca, Clovis, Eisai, Merck, Myriad, Roche/Genentech, Tesaro/GSK; Financial Interests, Personal, Other, Honorarium Consultant: Regeneron, Verastem, Zentalis; Financial Interests, Personal, Invited Speaker: Aadi; Financial Interests, Personal, Other, Speaker/Consultant: Adaptimune.