GYN cancer: competitive landscape updates from ESMO 2026

GSK, Lilly, and Merck/DSI presented promising early-phase ovarian cancer ADC data supporting rapid P3 development across ovarian cancer settings.

Mocertatug rezetecan (Mo-Rez, B7-H4 ADC; GSK)

Raludotatug deruxtecan (R-DXd, CDH6 ADC; Merck/Daiichi-Sankyo)

Sofetabart mipitecan (Sofe-M, FRα ADC; Lilly)

GSK’s longer P1 follow-up demonstrated durable Mo-Rez activity in PROC, although ILD and neutropenia remain a concern (LBA41). Complementing these monotherapy findings, Lilly (1247RO) and Merck/DSI (1246RO) reported encouraging ADC–bevacizumab combination data, emphasizing manageable safety

• Key Takeaways/Potential Implications
  • Updated P1 data demonstrated durable Mo-Rez activity with longer follow-up in 45 PROC pts treated at the P3 dose (5.8 mg/kg): mPFS was 11.1 mo, mDOR was 12.2 mo, and ORR remained 62%, consistent with prior SGO’26 data
    • Updated P1 data further clarified Mo-Rez’s safety profile, with ILD/pneumonitis reported at 7% (9 events, 1 Gr 3+; N=90) across both dose levels. High Gr 3+ neutropenia rates (60% at 5.8 mg/kg) prompted a strong recommendation for G-CSF prophylaxis across the BEHOLD program
    • This early phase data supported GSK’s advancement of Mo-Rez into three P3 studies across OC: BEHOLD-Ovarian03 in non-HRD 1L maintenance (+/- bev), BEHOLD-Ovarian02 in 2L PSOC (+ bev), and BEHOLD-Ovarian01 in PROC
  • The first P1 study data for Sofe-M + bevacizumab in 29 PSOC pts showed encouraging efficacy (79% ORR; 100% DCR), with similar ORR regardless of prior PARPi exposure, supporting P3 development in PARPi-naive and PARPi-treated subgroups
    • Gr 3+ safety events were reported to be infrequent, strengthening the data by demonstrating efficacy with favorable tolerability
    • These data provide the rationale for the Sofe-M + bev regimen in development for PARPi-naive and PARPi-treated PSOC pts in the ongoing P3 FRAmework trial
  • The first P1b data for R-DXd + bevacizumab in 30 PROC pts showed encouraging efficacy (cORR 80% at 4.8 mg/kg; 53% at 5.6 mg/kg). However, a Gr 5 event at 5.6 mg/kg was adjudicated as drug-related ILD
    • The data presented here provide the foundation for the combined R-DXd + bev regimen which has been aggressively advanced to three new P3 trials:  REJOICE-Ovarian04 in 1L maintenance (+/- bev), REJOICE-Ovarian03 in 2L PSOC (+/- bev), and REJOICE-Ovarian05 in 2L PSOC maintenance (+/- bev)

Mo-Rez

• Study information:
  • P1 BEHOLD-1: Mo-rez mono in 2-4L PROC; 1EP: ORR
  • N=45 for 5.8 mg/kg Q3W (RP3D; data from other 91 pts dosed at lower levels were excluded from below)
    • 97% evaluable pts showed B7-H4 tumor membrane positivity
• Efficacy:
  • cORR: 62% (5 CR & 23 PR)
  • mPFS: 11.1 mo 
  • mDOR: 12.2 mo 
• Safety:
  • Gr 3+ TRAEs: 71% 
    • Most common Gr 3+ TRAEs included: Neutropenia (60%), thrombocytopenia (16%), and anemia/asthenia (both 9%)  
    • ILD/pneumonitis occurred in 1 pt (2%) at the 5.8 mg/kg dose and 8 pts (18%; n=45) at the 4.8 mg/kg dose (8 out of 9 total events were Gr 1-2)
  • TRAEs leading to dose reduction (47%), interruption (51%), and discontinuation (2%) 
    • G-CSF prophylaxis was used in 8% of pts in the 5.8 mg/kg group

Sofe-M + bev

• Study information:
  • P1: Sofe-M (4 mg/kg IV Q3W) + bevacizumab in PSOC; 1EP: ORR, RP2D, safety
  • N= 33 PSOC pts; mF/U for PFS: 10.2 mo, mF/U for DOR: 6.2 mo
• Efficacy (N=29 evaluable):
  • cORR: 79% (6 CR & 17 PR)
    • Response rates were consistent across FRα expression levels (0-74% vs 75-100%) and prior PARPi exposure
  • mPFS & mDOR not reached 
• Safety:
  • Most common Gr 3+ TEAEs included: neutropenia (42%), anemia (24%), and thrombocytopenia (12%) 
  • AEs of interest: febrile neutropenia (3%; all Gr), stomatitis (36%; Gr 1/2), epistaxis (72%; Gr 1/2), neuropathy (9%; Gr 1/2) 
  • TRAEs leading to dose discontinuation: 6%

R-DXd + bev

• Study Information:
  • Cohort B1 of P1b/2 REJOICE-Ovarian02: R-DXd (4.8 or 5.8 mg/kg IV Q3W) + bevacizumab in 2-4L PROC; 1EP: ORR, safety and tolerability
  • N=30 (10/20)
• Efficacy (4.8 vs 5.8 mg/kg):
  • ORR: 80% (8/10) / 53% (8/15) 
• Safety (4.8 vs 5.8 mg/kg):
  • Gr 3+ TRAEs: 0% (0/10) / 40% (8/20) 
    • Drug-related ILD: 7% (2/30); one Gr 1 (4.8 mg/kg) and one Gr 5 (5.6 mg/kg), reported by investigator as aspiration pneumonia, later adjudicated as drug-related ILD
  • TRAEs leading to dose discontinuation: (10%/0%) 

Source: ESMO 2026