5511 Background: Gotistobart, an investigational tumor microenvironment-selective Treg depletion antibody targeting CTLA-4 with a novel mechanism of action, demonstrated anti-tumor activity when combined with prembrolizumab in the PRESERVE-004/GOG-3081 trial in patients (pts) with platinum-resistant ovarian cancer (PROC; Barlin et al., ESMO 2024). Here, we present overall survival (OS) and updated safety data from the Phase 2 trial (NCT05446298). Methods: Pts with PROC, 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 treated with gotistobart (1, 2, 3, or 6 mg/kg, Q3W) and pembrolizumab (200 mg, Q3W). Here we present data from patients that received 1 or 2 mg/kg gotistobart Q3W and pembrolizumab. Primary endpoints included objective response rate (ORR) based on RECIST 1.1 and safety. Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and OS. Results: As of November 12, 2025, 83 pts were treated with ≥1 dose of gotistobart in combination with pembrolizumab. Among them, 62 pts (85.5% White with a median age of 65 years and 83.9% with high grade serous OC) had received 1 or 2 mg/kg gotistobart, and 75.8% had received ≥3 lines of prior therapy (median 4, range: 1-10). The median time from randomization to database cutoff was 22.3 months (range 17.8, 27.2). Median OS was 18.9 m (95% CI 3.9, NE) and 8.3 m (95% CI 3.9 – 17.1) with the OS rates at 18 months at 54.3% (95% CI 35.1, 70.0) and 26.9% (95% CI 11.7 - 44.7) in pts that received 1 or 2 mg/kg gotistobart, respectively. Efficacy data are summarized in the table below. Grade ≥3 treatment-related (gotistobart or pembrolizumab) adverse events (TRAEs) were observed in 51.5% and 55.2% pts treated with 1 mg/kg or 2 mg/kg, respectively. Common (≥5%) grade ≥3 TRAEs were colitis (1 mg/kg: 12.1%, 2 mg/kg: 10.3%), hyponatremia (1 mg/kg: 12.1%, 2 mg/kg: 3.4%), increased ALT (1 mg/kg: 9.1%, 2 mg/kg: 3.4%), increased AST (1mg/kg: 9.1%, 2 mg/kg: 3.4%), adrenal insufficiency (1 mg/kg: 9.1%, 2 mg/kg: 3.4%), diarrhea (1 mg/kg: 9.1%, 2 mg/kg: 3.4%), and hypokalemia (1 mg/kg: 0%, 2 mg/kg: 6.9%). Conclusions: The chemotherapy-free combination of gotistobart and pembrolizumab demonstrated clinically meaningful ORR, OS and a manageable safety profile in pts with PROC, where the majority were heavily pretreated with no further standard-of-care treatment options. Clinical trial information: NCT05446298 . 1 mg/kg gotistobart + pembrolizumab(n=33) 2 mg/kg gotistobart + pembrolizumab(n=29) Confirmed ORR, % (95% CI) 21.2 (9.0, 38.9) 20.7 (8.0, 39.7) Median DoR, m (95% CI) 10.8 (3.3, NE) 11.6 (4.0, NE) Median PFS, m (95% CI) 2.2 (2.0, 4.2) 2.5 (1.9, 6.0) Median OS, m (95% CI) 18.9 (3.9, NE) 8.3 (3.9, 17.1) OS rate at 18 months, % (95% CI) 54.3 (35.1, 70.0) 26.9 (11.7, 44.7)
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