DARMSTADT, Germany — Merck KGaA, Darmstadt, Germany, said the first patient has been dosed in a Phase 3 trial evaluating its investigational antibody-drug conjugate precemtabart tocentecan in metastatic colorectal cancer.
The study, known as PROCEADE-CRC-03, is evaluating precemtabart tocentecan, or Precem-TcT, as a potential first-in-class anti-CEACAM5 antibody-drug conjugate for patients with metastatic colorectal cancer.
“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, MD, MBA, Global Head of R&D 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.”
The PROCEADE-CRC-03 trial will assess the safety and efficacy of Precem-TcT, alone or in combination with bevacizumab, in patients with metastatic colorectal cancer who are intolerant of, refractory to or whose disease has progressed after systemic therapies.
Merck KGaA said the study is expected to enroll about 1,020 patients across approximately 165 sites in 20 countries.
In a Phase 1 trial, known as PROCEADE-CRC-01, Precem-TcT as a monotherapy or in combination showed a predictable and manageable safety profile in more than 100 patients with heavily pretreated metastatic colorectal cancer, according to the company.
At the recommended dose for Phase 3 development, the confirmed objective response rate was 20.7%, median progression-free survival was 6.9 months and median overall survival had not been reached after a median follow-up of 13.1 months.
“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,” said Kanwal P.S. Raghav, MBSS, MD, 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 is the third-most commonly diagnosed cancer globally and the second-leading cause of cancer-related deaths. Merck KGaA said metastatic colorectal cancer was selected as the first indication for Precem-TcT because about 90% of colorectal cancers overexpress CEACAM5 and because patients whose disease has progressed after multiple prior therapies have limited treatment options.
Patients with advanced colorectal cancer often face worsening outcomes as the disease progresses, particularly after three or more lines of therapy, the company said.
