RC48G001 is a phase 2, open-label, multi-cohort study of disitamab vedotin (DV) alone or with Pembrolizumab in adults with locally advanced unresectable or metastatic urothelial cancer that expresses HER2.
Participants with the following types of urothelial cancer may be eligible:
- Cohort C: treatment-naive participants with LA/mUC
- Cohort G: participant with LA/mUC previously treated with enfortumab vedotin
Arms and Interventions

Cohort C
Population and HER2 Status:
Treatment-naïve LA/mUC HER2-expressing (HER2 IHC ≥1+)
Open-Label Study Treatment:
Disitamab vedotin ± pembrolizumab

Cohort G
Population and HER2 Status:
LA/mUC previously treated with EV HER2-expressing (HER2 IHC ≥1+)
Open-Label Study Treatment:
Disitamab vedotin monotherapy
Inclusion criteria
This is not a complete list of inclusion and exclusion criteria. Please connect with a Principal Investigator for further information.

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 therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the final 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 (2 is only allowed if certain criteria are met)

Cohort G
- Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
- Prior therapy:
- Received only 1 or 2 lines of prior systemic therapy for LA/mUC, including 1 line of therapy containing enfortumab vedotin, as monotherapy or in combination with pembrolizumab
- At least one measurable lesion by investigator assessment based on RECIST v1.1.
- 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 or 1
Exclusion criteria
This is not a complete list of inclusion and exclusion criteria. Please connect with a Principal Investigator for further information.

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 prior to the start of the 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 a study intervention
- 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 G:
- Known hypersensitivity to disitamab vedotin or any of their components
- Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks prior to the start of the study defined as Cycle 1 Day 1 for Cohort G
- Prior HER2-direct therapy
- Major surgery that has not fully recovered within 4 weeks prior to dose administration
- Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline
- Uncontrolled cardiac disease including cardiac failure, cardiac arrhythmia Grade ≥ 2, cardiac ischemia, or uncontrolled hypertension
- History of, or active, autoimmune disease that has required systemic therapy in the past 2 years

Primary outcomes
Cohort 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)
Cohort G:
- Objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR)

Secondary outcomes
- cORR per RECIST v1.1 by investigator assessment (Cohort C)
- Confirmed duration of response (DOR) per RECIST v1.1 by BICR (Cohort C)
- Confirmed DOR per RECIST v1.1 by investigator assessment (Cohort C)
- ORR per RECIST v1.1 by investigator assessment (Cohort G)
- DOR per RECIST v1.1, as assessed by BICR (Cohort G)
- DOR per RECIST v1.1, as assessed by investigator (Cohort G)
- Progression-free survival (PFS) per RECIST v1.1 by BICR (Cohorts C & G)
- PFS per RECIST v1.1 by investigator assessment (Cohorts C & G)
- Disease control rate (DCR) per RECIST v1.1 by BICR (Cohorts C & G)
- DCR per RECIST v1.1 by investigator (Cohorts C & G)
- Overall survival (OS) (Cohort C & G)
- Safety and tolerability (Cohorts C & G)
- PK parameters (Cohort C)
- Incidence of anti-drug antibodies (ADAs) (Cohort C)
Get started
Answer a 2-minute questionnaire and speak to a study representative.
A first step as you consider connecting with a Principal Investigator is to answer a 2-minute online questionnaire about your interest and willingness to be contacted. If your answers show the study might be a good fit for you and your patient, you may choose to have your contact information shared with a study clinic that you select for further discussion.
Get connected.
Your answers to these questions will only be linked to you if your responses indicate that you would like to be connected with a Principal Investigator and you choose to share your contact information with the study clinic. Pfizer study team members and our partners will have access to reports containing aggregated data that will not be directly linked back to you. Only the study staff can determine if your patient meets the study’s eligibility criteria and is able to enroll in the study.