Study of TU2218 in Combination With KEYTRUDA®(Pembrolizumab) in Patients With Advanced Solid Tumors

Required: PD-L1 (CD274) expression (CPS ≥1) (CPS ≥1)

head and neck squamous cell carcinoma (HNSCC) whose tumors express programmed death ligand 1 (PD - L1) [combined positive score (CPS) ≥1] as determined by an FDA-approved test

Required: MMR proficient mismatch repair (pMMR)

colorectal adenocarcinoma of Proficient Mismatch Repair (pMMR)/Microsatellite Stable (MSS) subtype, as determined by an FDA-approved test

Required: MSI microsatellite stable (MSS)

colorectal adenocarcinoma of Proficient Mismatch Repair (pMMR)/Microsatellite Stable (MSS) subtype, as determined by an FDA-approved test

Must have received: anti-PD-1/PD-L1 therapy — prior anti-PD-1/L1 mAb required for some cohorts (see extraction_notes)

If previously treated with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, PD-1 treatment progression is defined by meeting all of the following criteria: Has received at least 2 doses of an approved anti-PD-1/L1 mAb; Has demonstrated clinical progression after anti-PD-1/L1 mAb therapy; Progressive disease has been documented within 16 weeks from the last dose of anti-PD-1/L1 mAb

Must have received: platinum-based chemotherapy — HNSCC cohort, as applicable

recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy (as applicable)

Must have received: chemotherapy and targeted therapy — BTC cohort, as applicable

biliary tract cancer that has been locally advanced unresectable or metastatic or not tolerated prior standard first line chemotherapy and second line targeted therapy (as applicable)

Must have received: chemotherapy with biological agents — CRC cohort, at least 2 lines

colorectal adenocarcinoma...that has progressed on or not tolerated at least 2 lines of prior standard chemotherapy with biological agents where applicable

Cannot have received: anti-PD-1/PD-L1/PD-L2 or co-inhibitory T-cell receptor therapy

Exception: Phase 1b and BTC cohort: excluded if discontinued due to irAE; CRC and HNSCC cohorts: any prior anti-PD-1/PD-L1/PD-L2 or co-inhibitory T-cell receptor therapy excluded

For Phase 1b and BTC cohort in Phase 2a: discontinued prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137), due to an irAE. For CRC and HNSCC cohorts in Phase 2a: received prior therapy with an anti-PD-1, anti PD-L1, or anti PD-L2 agent or an agent directed to another stimulatory or co inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).

Cannot have received: systemic anti-cancer therapy including investigational agents

Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to treatment.

Cannot have received: radiotherapy

Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis.

Cannot have received: TGF-Beta pathway inhibitor

Received prior treatment targeting the signaling pathway of TGF-Beta