Merck KGaA's antibody-drug conjugate (ADC) precemtabart tocentecan has demonstrated safety and tolerability in a Phase Ib trial for patients with metastatic colorectal cancer (mCRC), with early efficacy signals suggesting potential advantages over current third-line therapies. The company presented these findings at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
Trial Design and Patient Population
The ongoing PROCEADE-CRC-01 study (NCT05464030) is investigating the dose, safety and tolerability of intravenous precemtabart tocentecan in approximately 200 patients with metastatic colorectal cancer. The study is evaluating two doses of the drug, 2.4mg/kg and 2.8mg/kg, administered every three weeks, while also examining early signs of efficacy.
Efficacy Outcomes
As of the March 25 data cut-off, 42% of patients enrolled in the dose expansion phase of the Phase Ib study remain on treatment, with three patients having continued treatment for nine months. The trial demonstrated a median duration of response (DoR) of 23.3 weeks, with nearly 60% of patients completing six cycles of treatment.
Key efficacy metrics showed a median progression-free survival (PFS) of 6.9 months and a 72% disease control rate at week 12. These results represent a significant improvement over current treatment options in this patient population.
Safety Profile
The safety profile of precemtabart tocentecan appeared manageable, with the most common adverse events being anemia and neutropenia. Notably, no cases of interstitial lung disease (ILD) or ocular toxicity were observed in the study. The trial reported no discontinuations or treatment-related deaths, suggesting a favorable tolerability profile.
Clinical Context and Expert Perspective
Scott Kopetz from the MD Anderson Cancer Center, one of the study investigators, emphasized the clinical significance of these results: "This ADC compares favourably versus the current monotherapy in third-plus line treated mCRC where response rates are in the single digits. Therefore, we think this represents a very active regimen, even in patients that have been previously treated with irinotecan as we're seeing in this population."
Mechanism of Action and Development Pipeline
Precemtabart tocentecan is an anti-CEACAM5 ADC that acts by selectively delivering a cytotoxic topoisomerase 1 inhibitor payload (exatecan). Beyond mCRC, the compound is being investigated in several oncology indications with CEACAM5 expression, including gastric cancer, non-small cell lung cancer, and pancreatic ductal adenocarcinoma in the ongoing Phase Ib/II PROCEADE-PanTumor study (NCT06710132).
Next Steps and Portfolio Context
Based on the positive data, Merck KGaA plans to advance precemtabart tocentecan in mCRC using the 2.8mg/kg dose. The company's ADC portfolio includes another compound, M3554, currently in Phase I clinical trials, along with two additional ADCs in preclinical development.
Market Landscape
The ADC market represents a rapidly growing segment of oncology therapeutics, valued at $8.6 billion in 2023 with expectations to exceed $45 billion by 2030, according to GlobalData analysis. The market already includes several blockbuster drugs such as Roche's Polivy (polatuzumab vedotin), Gilead Sciences' Trodelvy (sacituzumab govitecan), and Daiichi Sankyo/AstraZeneca's Enhertu (trastuzumab deruxtecan), with Enhertu being the highest grossing ADC currently available.
