Sanofi-Pfizer CEACAM5 ADC Trial Halted in Europe as Merck KGaA Advances Competing Asset to Phase 3
核心洞察
Sanofi and Pfizer's CEACAM5 (搜索)-targeting ADC tusamitamab sonditecan (搜索) has been placed on clinical hold in France, Spain, Sweden, and the Netherlands, though the specific reason remains undisclosed.
The halted ADC uses the same valine-lysine-glycuronide linker and topoisomerase 1 (搜索) inhibitor payload as Pfizer's discontinued PF-08046044, which was terminated due to increased toxicity.
Despite the setback, Merck KGaA plans to advance its competing CEACAM5 (搜索) ADC precemtabart tocentecan into phase 3 colorectal cancer (搜索) trials in Q2/Q3 2026, based on a 27% response rate in heavily pretreated patients.
Sanofi and Pfizer's CEACAM5 (搜索)-targeting antibody-drug conjugate tusamitamab sonditecan (搜索) has been placed on clinical hold across multiple European countries, marking another setback for the troubled target while competitor Merck KGaA prepares to advance its own CEACAM5 ADC into pivotal trials.
European Trial Suspension Raises Safety Concerns
The global phase 1 trial of tusamitamab sonditecan (搜索) has been halted in France, Spain, Sweden, and the Netherlands, according to the EU clinical trials registry. While no specific reason has been disclosed for the hold, the development adds to existing concerns about the asset's safety profile.
The ADC employs the same valine-lysine-glycuronide linker and topoisomerase 1 (搜索) inhibitor payload as Pfizer's discontinued PF-08046044, which the company terminated last year following increased toxicity in its phase 1 trial. This shared chemistry has raised questions about the viability of this particular drug design approach.
Adding to the complexity, tusamitamab sonditecan (搜索) uses the same antibody as Sanofi's previous CEACAM5 (搜索) attempt, tusamitamab ravtansine, which failed phase 3 in second-line non-small cell lung cancer (搜索) in 2023. Sanofi had switched focus to tusamitamab sonditecan following a 2022 collaboration with Seagen, which Pfizer subsequently acquired in 2023.
Merck KGaA Maintains CEACAM5 Confidence
Despite the setbacks facing Sanofi and Pfizer, Merck KGaA announced plans to advance its CEACAM5 (搜索)-targeting ADC precemtabart tocentecan into phase 3 development for colorectal cancer (搜索) in the second or third quarter of 2026. This move will make it the first anti-CEACAM5 ADC to enter pivotal development since Sanofi's tusamitamab ravtansine failed in the Carmen-LC03 trial two years ago.
The decision is based on phase 1 data from the Proceade-CRC-01 study, which showed a 27% response rate (12% confirmed) among 41 heavily pretreated colorectal cancer (搜索) patients receiving the recommended dose of 2.8mg/kg. The median progression-free survival of 6.9 months compared favorably against standard of care in this irinotecan-refractory population.
Precemtabart tocentecan also utilizes a topoisomerase 1 (搜索) inhibitor payload, similar to tusamitamab sonditecan (搜索), but appears to have demonstrated a more favorable safety and efficacy profile in early-stage testing.
Competitive Landscape Remains Active
Despite the challenges facing CEACAM5 (搜索) as a target, multiple companies continue development efforts. Bristol Myers Squibb (搜索) is advancing BMS-986490 in phase 1/2 trials for solid tumors (搜索), while BeOne (搜索)'s BG-C477 and Innovent (搜索)'s IBI3020 are also in phase 1 development.
The continued investment in CEACAM5 (搜索)-targeting therapies reflects the significant unmet medical need in heavily pretreated solid tumors (搜索), particularly colorectal cancer (搜索). However, the recent setbacks highlight the technical challenges in developing safe and effective ADCs against this target.
Pipeline Adjustments at Merck KGaA
Concurrent with advancing precemtabart tocentecan, Merck KGaA disclosed the discontinuation of two other oncology assets. The company terminated development of TEAD (搜索) inhibitor SW-682, which came through its $3.9 billion acquisition of SpringWorks (搜索), and confirmed the earlier discontinuation of PARP1 (搜索) inhibitor M9466.
The TEAD (搜索) inhibition field has faced broader challenges, with Novartis discontinuing IAG933 and Ikena terminating IK-930 after clinical disappointments. For PARP1 (搜索) inhibition, the competitive landscape featuring AstraZeneca's saruparib in three pivotal trials may have influenced Merck's decision to exit the space.