Merck KGaA’s antibody-drug conjugate (ADC), precemtabart tocentecan (Precem-TcT), has shown promising efficacy during an early-stage trial in heavily pre-treated colorectal cancer.
Thus far in the ongoing Phase I PROCEADE-CRC-01 study (NCT05464030), the drug has triggered an objective response rate (ORR) of 31% in patients at a dose of 2.8mg/kg.
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Precem-TcT also had a positive impact on progression-free survival (PFS), with the median value reaching 6.9 months in the treatment group, with a six month PFS rate of 64.3%.
Meanwhile, the drug was found to be safe and tolerable, with the most common Grade 3 treatment-emergent adverse events (TEAEs) being neutropenia and anaemia. While gastrointestinal (GI) TEAEs were observed, they were always mild-to-moderate, with no Grade 3 GI events recorded during the trial.
These results were first presented in a poster presentation at the ongoing 2025 European Society of Medical Oncology (ESMO) congress, which is being held in Berlin, Germany, on 17–21 October.
Precem-TcT functions by selectively targeting and killing cancer cells that express the surface protein carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).
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By GlobalDataThe outcome of the PROCEADE-CRC-01 study will be welcome news for Merck KGaA as the drug bested its potential rival, telisotuzumab adizutecan. In its respective Phase I study, the c-Met-targeting ADC triggered an ORR of 26.7%, according to a topline readout presented by AbbVie at ESMO.
Future directions for Precem-TcT
In conversation with Clinical Trials Arena, Victoria Zazulina, senior VP and head of development unit oncology at Merck KGaA, noted that the competition to commercialise a widely applicable ADC in colorectal cancer is stiff.
“The industry is on the brink of a breakthrough, though it is yet to be seen who makes it to market first,” she said.
In the world of ADCs, Zazulina believes that the “devil is in the detail”, as the type of chemotherapy you combine with a specific payload can play a key role in a drug’s efficacy and subsequent success.
“What we are learning as an industry is that the chemotherapy we want to direct to a disease such as colorectal cancer needs to be one that we know that indication will respond to,” Zazulina said.
“This has led to the explosion of ADCs using the Topoisomerase 1 (Top1) payload, which Precem-TcT employs.”
While Sanofi canned the development programme for its anti-CEACAM5 ADC tusamitamab in 2023, Zazulina noted that Merck KGaA has a “renewed interest” in the target, as a new payload class could demonstrate better efficacy in solid tumour indications.
To further explore this hypothesis, Merck KGaA will take Precem-TcT straight to Phase III trials in colorectal cancer, which Zazulina expects to initiate in the first half of 2026.
Combination could be key to early-line CRC treatment
Despite Precem-TcT’s promising clinical activity in colorectal cancer thus far, Zazulina believes that combination approaches “should not be disregarded”.
She stated: “Precem-TcT may be suitable as a monotherapy in later treatment settings, but in the first or second lines, it will most likely require a combination.”
This is primarily due to the higher prevalence of options in these settings, making it harder to best current standard of care (SoC) combination regimens like TAS-102 (trifluridine/tipiracil) plus bevacizumab.
Zazulina added: “Merck KGaA’s overall vision for ADCs like Precem-TcT aims to replace certain chemotherapy components, rather than to completely remove or outperform the whole regimen.”
Precem-TcT’s role in gastrointestinal cancers
While Zazulina noted that colorectal cancer was a perfect place to start in the Precem-TcT development journey due the company’s legacy and the disease’s strong expression of CEACAM5, Merck KGaA is eyeing the drug’s potential in further indications.
She commented: “There is this gastrointestinal theme around CEACAM5 expression, with indications like pancreatic and gastric cancer all showing reasonably high expression of CEACAM5.”
Despite many colorectal cancer patients expressing the CEACAM5 target, Merck KGaA will likely need to identify patients who may benefit from treatment with Precem-TcT, as “not everybody will exhibit the same level of target expression or ADC trafficking towards the tumour,” Zazulina caveats.
To explore its potential in gastrointestinal cancers and beyond, Merck KGaA is running trials in pancreatic, gastric and non-small cell lung cancer (NSCLC).
“All of our studies in these indications are currently recruiting patients, and we will soon be sharing results at some upcoming medical conferences,” Zazulina concluded.
Editor’s note: All references to MSD have been corrected to Merck KGaA throughout the copy.
The mechanism of action for Precem-TcT has been moved from paragraph 12 to paragraph 6.
The mention of oral presentation in paragraph 5 has been corrected to reflect the data was presented in a poster presentation.
Reference to the control arm for the Phase III trial in paragraph 18 has been removed.
