Sanofi and Pfizer get another conjugate blow

There have been doubts about Sanofi and Pfizer’s CEACAM5-targeting ADC tusamitamab sonditecan, and now the project’s global phase 1 trial has gone on hold in several European countries, according to the EU clinical trials registry. For now there are no details about the reason behind the hold, which affects sites in France, Spain, Sweden and the Netherlands, but there were already reasons to be cautious about this asset. First, it uses the same valine-lysine-glycuronide linker and topoisomerase 1 inhibitor payload as Pfizer’s ill-fated Adcetris follow-on PF-08046044, which the company discontinued last year following an increase in toxicity in that project’s phase 1 trial. Furthermore it recently emerged, with the reveal of tusamita-S’s international non-proprietary name, that the ADC employs the same antibody as Sanofi’s previous CEACAM5 attempt, tusamitamab ravtansine. Sanofi dropped that asset in 2023 after it failed phase 3 in second-line NSCLC, switching focus to tusamita-S, which came via a 2022 collaboration with Seagen; Pfizer bought Seagen in 2023. Others still developing anti-CEACAM5 ADCs include Merck KGaA with precemtabart tocentecan, soon to go into phase 3. More information on tusamita-S’s hold will be awaited, but it might be another bad omen for this target. Clinical-stage CEACAM5-targeting ADCsProjectCompanyDetailsNotePrecemtabart tocentecanMerck KGaATopo1i payloadPh3 in 3rd-line CRC to start Q2/Q3 2026BMS-986490Bristol Myers SquibbNone givenPh1/2 in solid tumours, +/- AvastinBG-C477BeOneTopo1i payloadPh1 in solid tumours, data due H2 2026IBI3020InnoventDual payloads (undisclosed)Ph1 in solid tumoursTusamitamab sonditecanSanofi/PfizerTopo1i payload, valine-lysine-glycuronide linkerPh1 in solid tumours; halted in France, Netherlands, Spain, SwedenSource: OncologyPipeline & clinicaltrials.gov.