Merck KGaA's antibody-drug conjugate precemtabart tocentecan (Precem-TcT) has demonstrated significant clinical activity in heavily pre-treated colorectal cancer patients, achieving a 31% objective response rate in an ongoing Phase I trial and positioning the company to advance directly to Phase III development.
Strong Efficacy Signals Drive Accelerated Development
The PROCEADE-CRC-01 study (NCT05464030) has shown that Precem-TcT triggers an objective response rate of 31% in patients at a dose of 2.8mg/kg. The antibody-drug conjugate also demonstrated a positive impact on progression-free survival, with the median value reaching 6.9 months in the treatment group and a six-month PFS rate of 64.3%.
These results, presented in a poster at the 2025 European Society of Medical Oncology (ESMO) congress in Berlin, Germany, represent a competitive advantage over rival therapies. The drug outperformed telisotuzumab adizutecan, AbbVie's c-Met-targeting ADC, which achieved an ORR of 26.7% in its respective Phase I study.
Favorable Safety Profile Supports Clinical Advancement
Precem-TcT was found to be safe and tolerable in the Phase I trial. The most common Grade 3 treatment-emergent adverse events were neutropenia and anemia. Notably, while gastrointestinal TEAEs were observed, they were consistently mild-to-moderate, with no Grade 3 GI events recorded during the trial.
The drug functions by selectively targeting and killing cancer cells that express the surface protein carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), utilizing a Topoisomerase 1 (Top1) payload.
Competitive Landscape and Strategic Positioning
Victoria Zazulina, senior VP and head of development unit oncology at Merck KGaA, noted that "the industry is on the brink of a breakthrough, though it is yet to be seen who makes it to market first." She emphasized that in the world of ADCs, the "devil is in the detail," as the type of chemotherapy combined 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 explained. "This has led to the explosion of ADCs using the Topoisomerase 1 (Top1) payload, which Precem-TcT employs."
While Sanofi discontinued development of its anti-CEACAM5 ADC tusamitamab in 2023, Zazulina noted renewed industry interest in the target, as new payload classes could demonstrate better efficacy in solid tumor indications.
Phase III Initiation Planned for 2026
Based on the promising Phase I results, Merck KGaA will advance Precem-TcT directly to Phase III trials in colorectal cancer, which Zazulina expects to initiate in the first half of 2026. This accelerated timeline reflects the company's confidence in the drug's clinical profile.
Combination Strategy for Early-Line Treatment
Despite Precem-TcT's promising clinical activity as a monotherapy, Zazulina believes combination approaches "should not be disregarded." She stated that "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 strategic approach acknowledges the competitive landscape in earlier treatment settings, where it becomes harder to outperform current standard of care combination regimens like TAS-102 (trifluridine/tipiracil) plus bevacizumab. Zazulina added that "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."
Broader Gastrointestinal Cancer Applications
While colorectal cancer represents the initial focus due to the company's legacy and the disease's strong expression of CEACAM5, Merck KGaA is exploring Precem-TcT's potential across multiple indications. Zazulina commented that "there is this gastrointestinal theme around CEACAM5 expression, with indications like pancreatic and gastric cancer all showing reasonably high expression of CEACAM5."
The company is currently 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.
However, patient selection will be crucial for success, as Zazulina noted that "not everybody will exhibit the same level of target expression or ADC trafficking towards the tumour," highlighting the need to identify patients who may benefit most from Precem-TcT treatment.
