Eisai and Merck announce termination of P3 Study with pembrolizumab + lenvatinib in 1L r/m Head and Neck Squamous Cell Carcinoma (HNSCC)

On August 25^th, 2023, Eisai and Merck announced the termination of their P3 LEAP-010 trial (PCD: Nov 2023) of pembrolizumab (KEYTRUDA; PD-1 mAb) + lenvatinib (LENVIMA; VEGFR1/2/3 TKI) vs pembrolizumab in 1L PD-L1 selected r/m HNSCC as the combination did not demonstrate an improvement in the primary endpoint of OS

Key Highlights & Implications:

• The companies shared that two planned interim analyses were conducted by an independent data monitoring committee over an 11-month period, with the latest analysis unable to demonstrate an improvement in OS for the combination arm when compared against pembrolizumab monotherapy,and the likelihood of reaching the protocol-specified threshold for statistical significance for OS deemed to be too low
  • The first analysis of the experimental arm showed a statistically significant improvement in PFS and ORR compared to the active comparator 
• Merck and Eisai are performing a full evaluation of the data of the trial which they plan to share with the scientific community, however, no timelines were disclosed
• The termination of LEAP-010 ends the development of one of the most advanced competitor combinations in development for the PD-L1 selected 1L r/m HNSCC space; No new entrants are expected to read out pivotal data in the near future
  • The P2 ASPEN-03 (PCD: Dec 2023) trial of evorpacept (SIRPa-Fc) + pembrolizumab is ongoing with the company previously communicating a readout by mid-2024
    • While ALX has previously stated that they believe the surrogate endpoint of 12m-OS is registration enabling, approval based on P2 data is very unlikely, especially given the recent P3 failures in this space
  • Immutep’s eftilagimod alpha (IMP321; LAG3 fusion protein) is also being assessed in combination with pembrolizumab in a P2 TACTI-003 (PCD: Dec 2023) with anticipated topline readout by year-end 2023  
• Despite the termination of LEAP-010, Eisai and Merck still have an active study currently recruiting in 2L r/m HNSCC P2 LEAP-009 (PCD: Aug 2024) assessing the same combination vs chemotherapy SOC 
• The termination of this trial reiterates the bar set by the current SOC as well as the need for robust randomized P3 trials to demonstrate efficacy (OS) improvements in patients