The antibody-drug conjugate precemtabart tocentecan in metastatic colorectal cancer

In a new phase I study, recently published on Nature Medicine, the anti-CEACAM5 antibody–drug conjugate precemtabart tocentecan (Precem-TcT) showed a predictable safety profile and an encouraging antitumor activity in 40 heavily pretreated patients with metastatic colorectal cancer.

CEACAM5, a cell surface glycoprotein that modulates cell adhesion, differentiation and proliferation, shows limited expression on healthy adult cells but is over-expressed in colorectal cancer and other solid tumors; with approximately 90% of colorectal cancers over-expressing CEACAM5, it is a rational therapeutic target. Precem-TcT is an innovative anti-CEACAM5 antibody–drug conjugate with the topoisomerase 1 inhibitor exatecan as its payload. Authors tested Precem-TcT on 40 heavily pretreated patients with irinotecan-refractory metastatic colorectal cancer; the maximum tolerated dose was determined to be 2.8 mg/kg every 3 week and after a median treatment of 19.1 weeks 7.5% of patients had confirmed partial responses. Median progression free survival was 6.7 months and 10% of patients remained on treatment at cutoff. As authors conclude, «The anti-CEACAM5 ADC Precem-TcT demonstrated a predictable safety profile and promising early efficacy in 40 heavily pretreated patients with metastatic colorectal cancer. Given the strong preclinical rationale and encouraging antitumor activity at tolerable doses (up to 2.8 mg/kg), the ongoing PROCEADE-CRC-01 study is exploring alternative administration schedules of Precem-TcT and combinations with bevacizumab with or without capecitabine or bevacizumab with 5-fluorouracil in this patient population with a high unmet need».