Merck avvia studio di fase 3 con patritumab deruxtecan (MK-1022; HER3-ADC) per il trattamento del carcinoma mammario HR+/HER2- (mBC) chemo naïve post-CDK4/6 inibitors e terapia endocrina (primo studio di fase III ADCs head to head in HR+/HER2- mBC)

Merck listed a new randomized, open-label Phase 3 HERTHENA-Breast04 trial evaluating patritumab deruxtecan (HER3-DXd, MK-1022; HER3-ADC) vs treatment of physician’s choice (TPC) in chemo naïve HR+/HER2- mBC post-CDK4/6i + ET (N=1000; PCD/SCD: Jul 2033)

• The study status is currently ‘Not, yet recruiting’ and it is anticipated to start in Aug 2025
• The trial will be divided into two arms: 
  • Experimental: HER3-DXd IV Q3W up to 13 months 
  • Active comparator: TPC of either CT or trastuzumab deruxtecan (T-DXd, Enhertu; HER2-ADC) IV Q3W up to 13 months 
• Primary endpoints: PFS up to 45 months and OS up to 85 months
• Secondary endpoints include ORR, DOR, QoL, and incidence of AEs
• Patritumab deruxtecan is being jointly developed by Merck and Daiichi Sankyo (DS), though DS is not listed as a study collaborator
• HERTHENA-Breast04 represents the first P3 trial evaluating patritumab deruxtecan in any breast cancer indication, and is expected to be registrational
  • The study patient population overlaps with Trodelvy’s label expansion population in ASCENT-07
  • The study also overlaps with AstraZeneca (AZ) and DS’s label for T-DXd based on DESTINY-Breast06 and is also the first P3 study comparing two ADCs head to head in HR+/HER2- mBC
• In May 2025, Merck and DS withdrew the BLA for HER3-DXd in NSCLC following two fatalities due to adjudicated ILD-related events that were reported from the P2 HERTHENA-Lung01 trial 
  • In its ASCO 2025 IR event, DS emphasized that it remains committed to HER3-DXd clinical development in eTNBC, citing the ongoing P2 HERTHENA-Breast03 trial
  • Moving ahead with HERTHENA-Breast04 reflects Merck and DS’s continued confidence in the potential of HER3-DXd despite he recent setbacks

Additional Background 

• HER3-DXd continues to be evaluated in the following relevant breast cancer trials:  
  • Phase 2 HERTHENA-Breast03: HER3-DXd + pembrolizumab (Keytruda; anti-PD-1) + CT in high-risk eTNBC and HR-low/positive/HER2- eBC 
  • Phase 1/2 ICARUS-BREAST02: HER3-DXd ± olaparib (Lynparza; PARPi) in aBC with prior T-DXd treatment