Urothelial carcinoma
Conditions
Interventions
Cohorts A, B, and D (Japan)
Disitamab vedotin 1.5 mg/kg administered intravenously (IV) every 2 weeks (Day 1 of each 2-week cycle)
Cohort C
- Single-arm part and combination arm of the randomized par
Sponsors
Kawai Norisuke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohorts A and B - Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including urothelial cancer (UC) originating from the renal pelvis, ureters, bladder, or urethra - Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy - At least one measurable lesion by investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) - Human epidermal growth factor receptor 2 (HER2)-expression status determined by the central laboratory to be immunohistochemistry (IHC) 1+, 2+ or 3+, in the provided tumor sample - Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Cohort C - Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra - No prior systemic therapy for LA/mUC *Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy - At least one measurable lesion by investigator assessment based on RECIST v1.1 - Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation - HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the provided tumor tissue sample - ECOG performance status of 0, 1, or 2 Cohort D (Japan) - Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra - Based on a participant's eligibility to receive treatment with standard of care therapies in Japan, participants must have received all of the following lines of therapy for LA/mUC: a. One prior line of platinum-containing chemotherapy. b. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second line treatment. c. Prior enfortumab vedotin therapy. - At least one measurable lesion by investigator assessment based on RECIST v1.1 - ECOG performance status of 0 or 1 Cohort E (Japan) - Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra - No prior systemic therapy for LA/mUC *Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy - At least one measurable lesion by investigator assessment based on RECIST v1.1 - Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation - HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample - ECOG performance status of 0 or 1
Exclusion criteria
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 monomethyl auristatin E (MMAE)-based antibody-drug conjugates (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 (Japan) - 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) - Any prior history of >= Grade 3 non-hematological adverse effects (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 (Japan) - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohorts A, B, and C - Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR) Cohorts D and E - Incidence of adverse events (AEs) - Incidence of dose alterations - Incidence of laboratory abnormalities - Incidence of electrocardiogram (ECG) abnormalities - Change from baseline of left ventricular ejection fraction (LVEF) - Pharmacokinetic (PK) parameter - Area under the curve (AUC) - PK parameter - Maximum concentration (Cmax) - PK parameter - Time to maximum concentration (Tmax) - PK parameter - Trough concentration (Ctrough) | — |
Secondary
| Measure | Time frame |
|---|---|
| Cohorts A, B, and C - cORR per RECIST v1.1 by investigator assessment - Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR - Confirmed DOR per RECIST v1.1 by investigator assessment - Progression-free survival (PFS) per RECIST v1.1 by BICR - PFS per RECIST v1.1 by investigator assessment - Disease control rate (DCR) per RECIST v1.1 by BICR - DCR per RECIST v1.1 by investigator - Overall survival - Incidence of AEs - Incidence of dose alterations - Incidence of laboratory abnormalities - Incidence of ECG abnormalities - Change from baseline of LVEF - PK parameter - AUC - PK parameter - Cmax - PK parameter - Tmax - PK parameter - Ctrough Cohort E - PK parameter of pembrolizumab - Cmax Cohorts C and E - Incidence of anti-drug antibodies (ADAs) against pembrolizumab All Cohorts - Incidence of ADAs against disitamab vedotin - Incidence of neutralizing antibodies against disitamab vedotin | — |
Countries
Argentina, Australia, Belgium, Canada, Chile, Israel, Italy, Japan, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed