• Participants with locally advanced, recurrent or metastatic histologically confirmed HNSCC, NSCLC, ESCC, CRC (left sided); locally advanced or recurrent disease must not be amenable to resection with curative intent

‣ Dose Escalation: Participants who have relapsed or progressed following prior anticancer therapy in the advanced/metastatic setting and for whom no approved or standard therapy is available.

⁃ Dose Exploration and Dose Expansion: The following tumor-specific criteria also apply. These cohorts will include all or a subset of these tumors.

∙ HNSCC - Received no more than 3 prior lines of therapy in the advanced or metastatic setting

∙ NSCLC - For participants with a targetable molecular alteration: received appropriate standard targeted therapy and no more than 2 prior lines of systemic chemotherapy in the advanced/metastatic setting. For participants without a targetable molecular alteration: received platinum-based chemotherapy and CPI (in combination or separately), and have received no more than 2 prior lines of systemic chemotherapy in the advanced/metastatic setting

∙ ESCC - Received no more than 3 prior lines of therapy in the advanced/metastatic setting

∙ CRC (left-sided) - For participants with a targetable molecular alteration (including dMMR or MSI-H): Received appropriate standard therapy for the alteration, at least 2 prior lines of systemic chemotherapy, and no more than 4 prior lines of therapy in the advanced/metastatic setting. For participants without a targetable molecule alteration: Received at least 2 prior lines of systemic chemotherapy (including an oxaliplatin-based chemotherapy), vascular endothelial growth factor (VEGF)-based therapy, and no more than 4 prior lines of therapy in the advanced/metastatic setting.

• Adequate Bone Marrow Function

• Adequate Renal \& Liver Function

• Adequate Performance Status