Merck KGaA (Merck) has dosed the first patient in its Phase III PROCEADE-CRC-03 trial, assessing the investigational anti‑carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) antibody-drug conjugate (ADC) precemtabart tocentecan (Precem TcT) for metastatic colorectal cancer (mCRC).

The trial is being conducted across nearly 165 sites in 20 countries and aims to enrol around 1,020 mCRC patients.

PROCEADE-CRC-03 is designed to assess the efficacy and safety of Precem-TcT, administered alone or in combination with bevacizumab, in mCRC patients who are intolerant of, refractory to, or have progressed after systemic therapies.

The rationale for this trial stems from the high unmet need in mCRC, where CEACAM5 is overexpressed in around 90% of cases, and options are limited for patients progressing after three or more lines of therapy.

In the earlier Phase I PROCEADE-CRC-01 study, Precem-TcT, either as a monotherapy or combined, demonstrated predictable and manageable safety in more than 100 heavily pretreated mCRC patients.

At the recommended Phase III dose of 2.8mg/kg every three weeks, including 29 patients, the confirmed objective response rate was 20.7% and the median progression-free survival was 6.9 months.

Median overall survival was not reached after a follow-up of 13.1 months.

Merck chief medical officer, research and development global head David Weinreich 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 III study and the enrolment 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.”

Precemtabart tocentecan is currently being studied in other tumour indications with high CEACAM5 expression, including gastric cancer, non-small cell lung cancer, and pancreatic ductal adenocarcinoma.

At the start of May, Merck dosed the first patient in its Phase III clinical programme, ELOWEN-1 and ELOWEN-2, evaluating the oral therapy enpatoran in individuals with lupus who have active skin manifestations.