Merck announced that the first patient has been dosed in the phase 3 PROCEADE-CRC-03 trial (NCT07549412). The study is evaluating precemtabart tocentecan (Precem-TcT), a potential first-in-class investigational anti-CEACAM5 Antibody Drug Conjugate (ADC), for the treatment of metastatic colorectal cancer (mCRC).

David Weinreich, MD, MBA, Global Head, R&D and Chief Medical Officer (CMO) for the Healthcare Business of Merck, said, “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. 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.”

The PROCEADE-CRC-03 study assesses the efficacy and safety of Precem-TcT, alone or with bevacizumab, in patients with mCRC who are intolerant- or refractory-to, or progressed after, systemic therapies. The PROCEADE-CRC-03 study will be conducted in approximately 165 sites in 20 countries and will recruit approximately 1,020 patients with mCRC.

In phase 1 (PROCEADE-CRC-01; NCT05464030), Precem-TcT as monotherapy or in combination showed predictable and manageable safety in more than 100 patients with heavily pretreated mCRC. At the recommended dose for phase 3 development (2.8 mg/kg Q3W; n=29), confirmed Objective Response Rate (cORR) was 20.7 percent (95 percent CI: 8.0, 39.7), median PFS was 6.9 months (95 percent CI: 4.4, 9.5) and median OS was not reached (95 percent CI: 8.7, NE) after a median follow-up of 13.1 months.

Kanwal PS Raghav, MBSS, MD, Department of Gastrointestinal Medical Oncology, MD, Anderson Cancer Center, Houston, said, “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. 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.”

Globally, CRC is the third-most commonly diagnosed malignancy and the second leading cause of cancer-related deaths. Merck chose mCRC as the first indication to assess the efficacy and safety of Precem-TcT because ~90 percent of colorectal cancers overexpress CEACAM5, and there is a high unmet clinical need in patients with metastatic colorectal cancer, especially among those who progressed on several previous therapies. Patients with advanced colorectal cancer typically face a challenging prognosis, with few options available for those whose disease continues to progress after three or more lines of therapy. Additionally, with progression, response to treatment and prognosis become increasingly worse over time.