Updated efficacy results from the phase 1 study of gotistobart (BNT316/ONC-392) in combination with lutetium Lu 177 vipivotide tetraxetan (Lu 177) in patients with metastatic castration-resistant prostate cancer (mCRPC).

175 Background: Lutetium-177 vipivotide tetraxetan (Lu 177) significantly improves progression-free survival (PFS) and overall survival (OS) in patients (pts) with pre-treated mCRPC. Combination strategies are being explored to enhance therapeutic outcomes. Preclinical models have demonstrated that radiotherapy selectively expands and activates regulatory T cells (Tregs) in the tumor microenvironment (TME). Gotistobart, an investigational pH-sensitive anti-CTLA-4 antibody, enhances Treg depletion in the TME and, combined with Lu 177, has demonstrated manageable safety and promising preliminary PSA50 rates in pts with mCRPC (#5067, ASCO 2025). Here, we report updated efficacy analyses from this Phase 1 trial. Methods: PRESERVE-006 (NCT05682443) is an open-label, randomized, phase 1/2 trial evaluating gotistobart with Lu 177 in pts with mCRPC post-androgen receptor pathway inhibition. Pts received gotistobart (3 mg/kg Q4W, 6 mg/kg Q6W, or 10 mg/kg Q6W, up to 13 doses) plus Lu 177 or Lu 177 alone (up to 6 doses). Efficacy endpoints were assessed per PCWG3 guideline. Results: As of August 8, 2025, this Phase 1 enrolled 25 pts who had a median age of 69 years (range: 52–86), 64.0% of the pts were White, 24.0% were Black and 4.0% were Asian. All pts had prior taxane and androgen receptor pathway inhibitors. Safety data for all 25 pts were reported at ASCO 2025, and no new safety signals were observed. With a median follow-up time of 11.9 m, median radiographic PFS (rPFS) was 4.8 m, 12.2 m, 8.3 m and not reached in the Lu 177 only, 3 mg/kg combo, 6 mg/kg combo, and 10 mg/kg combo group, respectively (Table). Among the 7 pts with measurable disease at baseline who received combination therapy, 5 (71.4%) achieved a partial response, and 2 pts achieved stable disease. Median PSA PFS was not reached for the cohorts dosed at 3 mg/kg and 6 mg/kg. Conclusions: Preliminary efficacy with a manageable safety profile was observed for gotistobart in combination with Lu 177 in pts with mCRPC during the Phase 1 study. The three arm randomized Phase 2 dose optimization stage (n=122) has completed enrollment at the 3 mg/kg combo, 6 mg/kg combo and Lu 177 only groups. Clinical trial information: NCT05682443 . Gotistobart 3 mg/kg + Lu 177(N = 6) Gotistobart 6 mg/kg + Lu 177(N = 6) Gotistobart 10 mg/kg + Lu 177(N = 6) Lu 177(N=7) Median follow-up time, m 17.8 9.2 11.9 12.3 Confirmed PSA50, n (%) (95% CI) 4 (66.7) (22.3, 95.7) 3 (50.0)(11.8, 88.2) 3 (50.0) (11.8, 88.2) 2 (28.6) (3.7, 71.0) PSA90, n (%) (95% CI) 3 (50)(11.8, 88.2) 0 (0.0, 45.9) 2 (33.3)(4.3, 77.7) 1 (14.3)(0.4, 57.9) Median rPFS, m(95% CI) 12.2(2.0, NE) 8.3(5.8, NE) Not reached (11.0, NE) 4.8(3.8, NE) 6m rPFS rate, (%) (95% CI) 66.7(28.9, 100) 75.0(32.6, 100) 83.3(53.5, 100) 28.6(0, 62.0) Median PSA-PFS, m (95% CI) Not reached(9.72, NE) Not reached (5.39, NE) 10.4(4.8, NE) 4.9(4.4, 6.0)