A Study of Disitamab Vedotin Alone or With Pembrolizumab in Urothelial Cancer That Expresses HER2

Exclusion Criteria

• •Cohorts A and B
• •Known hypersensitivity to disitamab vedotin or any of their components
• •Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohorts A and B)
• •Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
• •Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
• •Major surgery that has not fully recovered within 4 weeks prior to dose administration
• •Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline
• •Cohort C
• •Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components
• •Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study defined as Cycle 1 Day 1 for the single-arm part of Cohort C and as randomization date for the randomized part of Cohort C)
• •Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
• •Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
• •Major surgery that has not fully recovered within 4 weeks prior to dose administration
• •Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline
• •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
• •Participants who have previously received any prior treatment with an agent directed to another stimulatory or co-inhibitory T cell receptor (including but not limited to CD137 agonists, CAR-T cell therapy, CTLA-4 inhibitors, or OX-40 agonists) are excluded.
• •Cohort D
• •Known hypersensitivity to disitamab vedotin or any of their components
• •Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort D)
• •Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
• •Prior HER2-directed therapy
• •Any prior history of ≥ Grade 3 non-hematological AEs related to prior therapy
• •Major surgery that has not fully recovered within 4 weeks prior to dose administration
• •Peripheral sensory or motor neuropathy ≥ Grade 1 at baseline
• •Cohort E
• •Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components
• •Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort E)
• •Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
• •Any prior history of ≥ Grade 3 non-hematological AEs related to prior therapy
• •Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
• •Major surgery that has not fully recovered within 4 weeks prior to dose administration
• •Peripheral sensory or motor neuropathy ≥ Grade 1 at baseline
• •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
• •Cohort G
• •Known hypersensitivity to disitamab vedotin or any of their components
• •Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort G)
• •Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
• •Prior HER2-directed therapy
• •Major surgery that has not fully recovered within 4 weeks prior to dose administration
• •Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline