TroFuse-022/ENGOT-ov84/GOG-3103 part 2: A phase 3 study of maintenance therapy with sacituzumab tirumotecan ± bevacizumab vs standard of care following second-line platinum-based doublet chemotherapy for platinum-sensitive recurrent ovarian cancer.

Abstract

TPS5636 Background: There is an unmet clinical need for novel therapies for patients with platinum-sensitive recurrent ovarian cancer (PSROC). Trophoblast cell-surface antigen 2 (TROP2) is highly expressed in multiple tumor types, including ovarian cancer. Sacituzumab tirumotecan (sac-TMT) is a TROP2-directed antibody-drug conjugate with a unique, bifunctional linker that maximizes delivery of a belotecan-derived topoisomerase 1 inhibitor payload to tumor cells. The current TroFuse-022/ENGOT-ov84/GOG-3103 study (NCT06824467) is evaluating maintenance therapy with sac-TMT ± bevacizumab (bev) vs standard of care (SoC) following second-line (2L) platinum-based doublet chemotherapy (chemo) in participants (pts) with PSROC. The study includes a safety run-in part (part 1) and a phase 3 part (part 2). We present the trial design for part 2 of this study. Methods: Part 2 is enrolling ~750 pts aged ≥18 y with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with PSROC (radiographic evidence of PD >180 d after the last dose of first-line [1L] platinum-based doublet chemo ± bev); pts with BRCA mutation or homologous recombination deficiency-positive status with no evidence of disease (NED), CR, or PR after 1L chemo must have received a PARP inhibitor as 1L maintenance therapy. All pts must have received 6 cycles of 2L carboplatin-based doublet chemo ± bev and achieved NED, CR, PR, or SD per investigator assessment; pts with SD must have received bev in combination with 2L chemo and be eligible to continue treatment with bev. Other inclusion criteria are an ECOG PS of 0 or 1 and an available tumor sample for central testing of TROP2 and BRCA status. Candidates for curative-intent surgery or radiotherapy at enrollment are not eligible. Pts are randomized 1:1 to receive maintenance therapy with sac-TMT 4 mg/kg IV Q2W ± bev 15 mg/kg IV Q3W (arm 1) or SoC treatment with observation ± bev 15 mg/kg IV Q3W (arm 2). Use of bev is at the investigator’s discretion and can only be given to eligible pts who received ≥2 doses of bev 15 mg/kg Q3W or equivalent dose (with no dose reductions) in combination with 2L chemo; pts with SD after 2L chemo must receive bev (pts with SD not receiving bev are ineligible). Treatment with sac-TMT (arm 1) and bev (if elected, arms 1 and 2) continues until PD, unacceptable toxicity, or other protocol-defined reason for discontinuation. Pts in arm 2 are not permitted to cross over to arm 1. The primary endpoint is PFS per RECIST version 1.1 as assessed by blinded independent central review. Secondary endpoints include OS, safety and tolerability, and patient-reported outcomes. PFS and OS will be assessed in pts with medium/high TROP2 expression tumors and all pts. The study is ongoing, and enrollment in part 2 is open. Clinical trial information: NCT06824467; EU CT, 2023-508015-23; UTN, U1111-1297-4489.