Treatment options for recurrent or metastatic cervical cancer (r/mCC) remain limited. We evaluated the efficacy and safety of tisotumab vedotin (TV)-based combinations with standard agents in first-line (1L) and previously treated (second-line or later [2L+]) settings in r/mCC. innovaTV 205/ENGOT-cx8/GOG-3024 (NCT03786081) was a multicenter, open-label phase 1b/2 study, which included dose-expansion arms of 1L TV + carboplatin (arm D), 1L/2L+ TV + pembrolizumab (arms E/F), and 1L TV + carboplatin + pembrolizumab ± bevacizumab (arm H). The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). As of October 15, 2025, 139 patients were enrolled in dose-expansion arms D (n = 33), E (n = 33), F (n = 35), and H (n = 38). Confirmed ORR (median DOR) was 54.5% (8.6 months), 40.6% (not reached), 35.3% (18.2 months), and 65.8% (13.3 months) in arms D-F and H, respectively. Median PFS was 6.9, 5.3, 5.6, and 10.6 months; median OS was 25.5, 30.7, 15.3, and 28.0 months. Grade ≥ 3 AEs related to any treatment component occurred in 72.7%, 45.5%, 48.6%, and 86.8% of patients; AEs leading to TV discontinuation occurred in 24.2%, 24.2%, 34.3%, and 55.3% of patients in arms D-F and H, respectively. With ≥ 5 years of follow-up, TV doublet combinations demonstrated durable activity consistent with previous findings and encouraging long-term OS in 1L and 2L+ r/mCC, with no new safety signals. The 1L TV-based triplet/quadruplet regimen showed meaningful antitumor activity with expected toxicity.

Objective: To evaluate the clinical benefit of platinum rechallenge in patients with platinum-resistant ovarian cancer (PROC) and to explore the predictive role of BRCA mutation status. Methods: We retrospectively evaluated platinum rechallenge in PROC at Vall d’Hebron University Hospital between 2010 and 2023. Eligibility required ≥1 prior non-platinum regimen and ≥12 months since the last platinum dose. Objective response rate (ORR) per RECIST 1.1 and survival outcomes were analyzed by BRCA status and prior treatment lines. Results: ORR was 57% (95%CI, 42.1–73.0%) in the overall cohort (n = 63), 77% in BRCA-mutated patients (n = 13), and 50% in BRCA wild-type patients (n = 46). Median progression-free survival (PFS) was 7.3 months overall, which was longer in BRCA-mutated versus BRCA wild-type patients (8.4 vs. 7.4 months; HR 0.47, 95%CI 0.23–0.94; p = 0.033). An exploratory subgroup analysis suggested longer PFS among BRCA-mutated patients with ≤4 prior lines; however, this small subgroup finding should be considered hypothesis-generating. A platinum-free interval >6 months after rechallenging was observed in 38.5% of BRCA-mutated versus 13% of BRCA wild-type patients. Conclusions: Platinum rechallenge showed clinically meaningful activity in selected patients with PROC after an extended interval of intervening non-platinum therapy. These findings support the concept that platinum sensitivity may be dynamic and suggest that BRCA status and clinical selection factors may help inform individualized treatment sequencing in the post-PARP inhibitor era. Prospective validation with broader molecular characterization is warranted.