Upfront Trastuzumab-Deruxtecan Plus Capecitabine and Bevacizumab for Patients With HER-2 Positive Metastatic Colorectal Cancer.

This is a multinational, Open-label, Single-arm Phase II trial in which patients with metastatic or locally advanced unresectable HER-2 positive colorectal cancer will receive upfront trastuzumab-deruxtecan, capecitabine and bevacizumab until progressive disease, unacceptable toxicity, consent withdrawal, investigator's decision or study termination, whichever occurs first. The primary endpoint of the study is Overall Response Rate by blinded independent central review. In order to preliminarily assess safety, a safety run-in phase will be conducted. The safety run-in phase will include the first 6 patients enrolled. After 6 patients will have received 3 cycles of study treatment, enrollment will be interrupted. A Safety Monitoring Committee (SMC) will review safety data (including demographics, adverse events, serious adverse events, adverse events of special interest, and relevant laboratory data). The SMC will then provide a recommendation as to whether the study may continue, whether amendment(s) to the protocol should be implemented, or whether the study should be stopped. Recruitment will only be resumed accordingly to SMC decision.