Like Sanofi, German Merck keeps the CEACAM5 faith
Precemtabart tocentecan could soon become the industry's most advanced anti-CEACAM5 ADC.
Precemtabart tocentecan could soon become the industry's most advanced anti-CEACAM5 ADC.
Merck KGaA’s precemtabart tocentecan is set to become the first anti-CEACAM5 antibody-drug conjugate to enter pivotal development since Sanofi’s tusamitamab ravtansine crashed in the phase 3 Carmen-LC03 trial two years ago.
Merck’s planned move, revealed on Thursday in its quarterly results, is especially risky given that it’s backed only by phase 1 data, and the company’s track record in oncology is patchy – a fact of which investors have been reminded with the discontinuation of two more phase 1 projects. But Sanofi is also keeping the faith in CEACAM5, advancing a follow-up to tusamita-R that uses a different payload.
Sanofi’s follow-up anti-CECAM5 ADC, tusamitamab sonditecan, uses a topoisomerase 1 inhibitor payload, and it was only when its INN was published last month that it became apparent that it uses the same antibody as the earlier discontinued tusamita-R. Merck’s precemta-T also uses a topoisomerase 1 inhibitor payload.
Colorectal cancer
On Thursday Merck revealed plans to start a phase 3 study of precemta-T in colorectal cancer in the second or third quarter of the year. The basis for this appears to be a 27% response rate (12% confirmed) among 41 heavily pretreated colorectal cancer patients given the go-forward dose of 2.8mg/kg in the phase 1 Proceade-CRC-01 study, as reported at ASCO-GI in January.
This might not seem too impressive, but the activity was described as clinically meaningful, and median PFS of 6.9 months compared favourably against standard of care in this irinotecan-refractory population. It will be interesting to see if Merck mandates CEACAM5 expression in phase 3, given that this correlated with activity in Sanofi’s failed Carmen-LC03 study, though that was in lung cancer.
Sanofi’s follow-up, tusamita-S, is in a phase 1 solid tumour trial that lists colorectal cancer as one of its main targets. The start of phase 3 will make Merck’s precemta-T the most advanced anti-CEACAM5 ADC in development, according to OncologyPipeline.
Recent changes in Merck KGaA’s oncology pipeline
| Mechanism | Project | Status | Competition | Note |
|---|---|---|---|---|
| CEACAM5 ADC | Precemtabart tocentecan | To enter ph3 in colorectal cancer in Q2/Q3 2026 | Bristol Myers Squibb’s BMS-986490 in ph1/2; Sanofi’s tusamitamab sonditecan, Innovent’s IBI3020 & BeOne’s BG-C477 in ph1 | Sanofi discontinued tusamitamab ravtansine after failing ph3 Carmen-LC03 trial in 2L NSCLC |
| Tead inhibitor | SW-682 | Discontinued | Vivace’s VT3989, Orion’s ODM-212 & TYK’s TY-1054 in ph2 | Project came through $3.9bn acquisition of SpringWorks in Apr 2025; Novartis discontinued IAG933, Ikena discontinued IK-930 |
| PARP1 inhibitor | M9466/ HRS-1167 | Discontinued | AstraZeneca’s saruparib in ph3, AZD9574 (CNS-penetrant) in ph1/2; Gilead’s ex-Xinthera GS-0201 in ph1 | Project licensed from Jiangsu HengRui for €160m up front in Oct 2023; Merck earlier discontinued Nerviano’s PARP1 inhibitor NMS-293 |
Source: OncologyPipeline.
At the same time as moving to advance precemta-T into phase 3, Merck revealed the scrapping of the TEAD inhibitor SW-682, and confirmed the earlier rumoured discontinuation of the PARP1 inhibitor M9466.
No clinical data had been reported for SW-682, but the molecule came through Merck’s $3.9bn acquisition of SpringWorks, whose main attractions were the approved drugs Ogsiveo and Gomekli. TEAD inhibition has underwhelmed previously, with Novartis discontinuing IAG933 last year, and Ikena throwing in the towel on IK-930 in 2024; both had disappointed in the clinic.
The situation in PARP1 inhibition is different, in that this field has become competitive, featuring AstraZeneca’s saruparib in three pivotal trials, and several other clinical-stage projects. It’s possible that Merck simply didn’t think its M9466 could compete; last year the project’s DDRiver-521 study was withdrawn from clinicaltrials.gov, while DDRiver-511 was terminated, and on Thursday Merck removed M9466 from its pipeline.
M9466, which Merck licensed from Jiangsu HengRui, was Merck’s second shot at PARP1. In 2022 the German company licensed rights to Nerviano’s NMS-293, but gave up on that a year after doing the HengRui deal.
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