Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Orange, California and other locations
Dates
study started
completion around
Principal Investigator
by Nataliya Mar

Description

Summary

This study is being done to see if a drug called disitamab vedotin, alone or with pembrolizumab, works to treat HER2 expressing urothelial cancer. It will also test how safe the drug is for participants.

Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).

It will also study what side effects happen when participants get the drug. A side effect is anything a drug does to your body besides treating the disease.

Official Title

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

Keywords

Urothelial Carcinoma, Urothelial Cancer, Bladder Cancer, HER2 Mutations, HER2 Overexpression, HER2 Amplification, RC48, Seattle Genetics, Carcinoma, Transitional Cell Carcinoma, Pembrolizumab, Disitamab vedotin, DV monotherapy for HER2-positive tumor types, DV monotherapy for HER2-low tumor types

Eligibility

You can join if…

Open to people ages 18 years and up

Cohorts A and B

  • Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including 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 RECIST version 1.1.
  • HER2-expression status determined by the central laboratory to be 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

  • 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:
      1. One prior line of platinum-containing chemotherapy.
      1. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second line treatment.
      1. 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

  • 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

You CAN'T join if...

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

There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Locations

  • University of California Irvine Medical Center accepting new patients
    Orange California 92868 United States
  • University of California Los Angeles Medical Center accepting new patients
    Los Angeles California 90095 United States
  • Kaiser Permanente Southern California accepting new patients
    Riverside California 92505 United States

Lead Scientist at UC Irvine

  • Nataliya Mar
    Associate Clinical Professor, Medicine, School of Medicine. Authored (or co-authored) 31 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Seagen Inc.
ID
NCT04879329
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 332 study participants
Last Updated