Merck Germany, has launched a major late-stage push in metastatic colorectal cancer.

 

The global pharma powerhouse has announced that the first patient has been dosed in its Phase 3 trial evaluating precemtabart tocentecan (Precem-TcT), a potential first-in-class anti-CEACAM5 antibody-drug conjugate.

 

The study -- PROCEADE-CRC-03 -- marks a key milestone for the company’s oncology pipeline, advancing a novel ADC designed to target CEACAM5 in metastatic colorectal cancer (mCRC) using an exatecan-based payload. 

 

The trial will assess Precem-TcT, both as monotherapy and in combination with bevacizumab, in patients whose disease has progressed after or become resistant to standard treatments. It will span approximately 165 sites across 20 countries and enroll around 1,020 patients.

 

“Leveraging our novel payload-linker technology, Precem-TcT is the first CEACAM5-targeted ADC in clinical studies with an exatecan payload, rationally designed for stability and enhanced cancer cell killing activity,” said David Weinreich, Global Head, Research and Development and Chief Medical Officer, Merck KGaA, Darmstadt, Germany. 

 

“The Phase 3 study and the enrollment of the first patient with Precem-TcT, build on the Company’s more than 20 years of expertise in colorectal cancer, and highlight our commitment to advancing differentiated ADCs for heavily pretreated patients with limited treatment options.”

 

Early clinical evidence is already shaping confidence in the program. In Phase 1, involving more than 100 heavily pretreated patients, Precem-TcT showed a manageable safety profile. 

 

At the Phase 3 dose, the confirmed objective response rate was 20.7%, with median progression-free survival of 6.9 months and overall survival not yet reached after 13.1 months of follow-up.

 

“The PROCEADE-CRC-03 Phase 3 study is designed to address significant unmet needs for patients with metastatic colon cancer whose disease has progressed after standard therapies,” Kanwal P.S. Raghav, Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston. 

 

“The data from the phase 1 study suggested a manageable safety profile for Precem-TcT and encouraging early tumor response in the patients with heavily pre-treated metastatic colorectal cancer. CEACAM5 is largely absent from healthy tissues and is overexpressed in nearly all mCRC cases, supporting a non-selective, universal patient approach, and represents a promising therapeutic target in this setting.”

 

Colorectal cancer remains a major global burden, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths.