RC48G001 (JCP126)

A Phase 2 Multi-Cohort, Open-Label, Multi-Center Clinical Study Evaluating the Efficacy and Safety of Disitamab Vedotin (RC48-ADC) in Subjects with HER2-Expressing Locally-Advanced Unresectable or Metastatic Urothelial Carcinoma

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Population: Urothelial Carcinoma - LA/mUC HER2+

Line of therapy: 2L

Intervention: 

• Cohorts A and B: Disitamab Vedotin (RC48-ADC) IV q2weeks in previously-treated subjects with LA/mUC

• Cohort C: evaluation of Disitamab Vedotin (RC48-ADC) +/- Pembro in treatment-naive subjects with LA/mUC

Key Inclusion Criteria

1. LA/mUC with histopathological confirmation, including UC originating from the renal pelvis, ureters, bladder, or urethra. Mixed-cell type tumors are eligible as long as urothelial cell carcinoma is the predominant cell type.

2. Cohort C: No prior systemic therapy for LA/mUC; must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy

3. Cohorts A and B: Subject must have received 1 or 2 lines of prior systemic therapy for LA/mUC, including 1 line of platinum-containing chemotherapy.

   - Neoadjuvant or adjuvant therapy, with progression within 12 months of completing therapy, is considered a line of prior therapy.

   - Maintenance avelumab therapy delivered following first-line platinum therapy is not considered a separate line of therapy.

   - Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first line maintenance therapy or as second line treatment are allowed

4. Radiographically documented disease progression during or after the most recent line of therapy for LA/mUC

5. At least one measurable lesion based on RECIST v1.1.

6. HER2-expressing status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the most recent archival or fresh tumor tissue sample of muscle-invasive or metastatic UC.

7. A tumor tissue sample must be supplied. If an archival tumor tissue sample is not available, the subject must have a tumor lesion available for biopsy

8. ECOG 0 or 1 (2 allowed for Cohort C)

9. Adequate cardiac, bone marrow, hepatic, renal, and coagulation functions

   
   

Key Exclusion Criteria

1. Received anti-tumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) or participated in another clinical study <3 weeks prior to the start of the study

2. Toxicity from a previous treatment has not returned to Grade 0-1 (except for Grade 2 alopecia)

3. Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy

4. Major surgery that has not fully recovered <4 weeks prior to dose administration

5. Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline

6. Received live or live-attenuated vaccines <4 weeks prior to study treatment initiation or plan on receiving such vaccines during the course of study treatment

7. Subjects with acute, chronic or symptomatic infection

8. Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interpretation of outcomes, including active opportunistic infections or advanced (severe) infections, or uncontrolled diabetes

9. Uncontrolled cardiac disease

10. History of other malignant tumors within 5 years prior to dose administration, (exceptions in protocol e.g. prostate cancer T2NXMX or lower, with Gleason score ≤7)

11. Subjects with active central nervous system (CNS) metastases (exceptions in protocol)

12. Active autoimmune diseases that require systemic therapy (such as the use of disease-modifying drugs [eg, methotrexate, sulfasalazine, leflunomide, hydroxychloroquine], corticosteroids, or immunosuppressives) over the past 2 years. Replacement therapies (such as thyroxine, insulin, or physiological replacement of glucocorticoids due to renal or pituitary deficiency) are allowed

13. Received hematopoietic stem cell transplantation or solid organ transplantation

14. Pleural effusion or ascites with symptoms or requiring symptomatic treatment

15. Any other disease, metabolic disorder, or abnormal finding upon physical examination or laboratory examination that makes the subject unsuitable for receiving the investigational drug, affects the interpretation of study outcomes, or poses risks to subject safety, as determined by the investigator

Sponsor: Seagen Inc.

CRP Contact: rhythm.sharma@ladydavis.ca

CRP PI: Dr. A. Rose

Status: Open to accrual