TroFuse-036/GOG-3123/ENGOT-cx22: A 2-part, phase 3, randomized study of sacituzumab tirumotecan (sac-TMT) + pembrolizumab (pembro) ± bevacizumab (bev) vs standard of care (SoC) as first-line maintenance therapy for PD-L1–positive cervical cancer.

Abstract

TPS5628 Background: First-line pembro + platinum-doublet chemo ± bev is the preferred SoC for PD-L1-positive stage IVB, persistent, or recurrent cervical cancer. However, ~50% of patients experience progressive disease (PD) within 1 y, highlighting the need for first-line maintenance therapies that can extend clinical benefit. Sac-TMT is a TROP2-directed antibody-drug conjugate with a unique, bifunctional linker that maximizes payload delivery to tumor cells. In a prior phase 2 basket study, sac-TMT + pembro demonstrated promising antitumor activity (ORR, 58% [22/38]) with a manageable safety profile in participants (pts) with recurrent or metastatic cervical cancer that progressed on or after platinum-doublet chemo. TroFuse-036/GOG-3123/ENGOT-cx22 (NCT07216703) is evaluating first-line maintenance therapy with sac-TMT + pembro ± bev vs SoC in pts with cervical cancer. Methods: This 2-part, phase 3, randomized, open-label study is enrolling pts aged ≥18 y with persistent, recurrent, or newly diagnosed stage IVB squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment (surgery/radiation), ECOG PS of 0 or 1, and PD-L1 combined positive score ≥1. In part 1 (safety run-in), ~20 eligible pts who complete 6 cycles of induction therapy with pembro 200 mg Q3W + paclitaxel 175 mg/m 2 Q3W + cisplatin 50 mg/m 2 (or carboplatin AUC 5 mg/mL/min Q3W) + bev 15 mg/kg Q3W without PD per investigator will receive maintenance therapy with sac-TMT 4 mg/kg Q2W + pembro 400 mg Q6W for ≤14 6-wk cycles + bev 15 mg/kg Q3W until treatment discontinuation criteria are met. Enrollment in part 2 will start after enrollment in part 1 is complete. In part 2, ~1003 eligible pts will receive 6 cycles of induction therapy (same doses as in part 1) with pembro + platinum-doublet chemo ± bev at investigator discretion. For randomization to maintenance therapy, pts must complete induction therapy and have CR, PR, or SD per RECIST v1.1 by investigator as assessed by an evaluable tumor scan at week 18; evaluable TROP2 expression; and resolution of any AEs to grade ≤1. After part 1 safety data review is complete, ~802 eligible pts in part 2 maintenance part will be randomized 1:1 to receive sac-TMT 4 mg/kg Q2W + pembro 400 mg Q6W for ≤14 6-wk cycles ± bev 15 mg/kg Q3W or SoC with pembro 400 mg Q6W for ≤14 6-wk cycles ± bev 15 mg/kg Q3W; bev use is at investigator discretion and continues until treatment discontinuation criteria are met. The primary endpoint is safety in part 1 and PFS per RECIST v1.1 by blinded independent central review and OS with maintenance therapy in part 2. Secondary endpoints associated with maintenance therapy in part 2 are PFS2 per investigator, safety, and patient-reported outcomes. Enrollment began in Dec 2025. Clinical trial information: NCT07216703 .