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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04879329
Recruitment Status : Recruiting
First Posted : May 10, 2021
Last Update Posted : January 5, 2023
Sponsor:
Collaborators:
RemeGen Co., Ltd.
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Seagen Inc.

Study Description
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Brief 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.


Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Drug: disitamab vedotin Drug: pembrolizumab Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Multi-Cohort, Open-Label, Multi-Center Clinical Study Evaluating the Efficacy and Safety of Disitamab Vedotin (RC48-ADC) Alone and in Combination With Pembrolizumab in Subjects With Locally-Advanced Unresectable or Metastatic Urothelial Carcinoma That Expresses HER2
Actual Study Start Date : May 3, 2022
Estimated Primary Completion Date : October 31, 2024
Estimated Study Completion Date : March 31, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort A - DV monotherapy for HER2-positive tumor types
Disitamab vedotin monotherapy
 Drug: disitamab vedotin
Given into the vein (IV; intravenous) every 2 weeks.
Other Name: RC48, RC48-ADC
Experimental: Cohort B - DV monotherapy for HER2-low tumor types
Disitamab vedotin monotherapy
 Drug: disitamab vedotin
Given into the vein (IV; intravenous) every 2 weeks.
Other Name: RC48, RC48-ADC
Experimental: Cohort C - Non-randomized combination therapy
Disitamab vedotin + pembrolizumab
 Drug: disitamab vedotin
Given into the vein (IV; intravenous) every 2 weeks.
Other Name: RC48, RC48-ADC

Drug: pembrolizumab
Given by IV on Day 1 of each 6-week cycle.
Other Name: Keytruda
Experimental: Cohort C - Randomized combination therapy
Disitamab vedotin + pembrolizumab
 Drug: disitamab vedotin
Given into the vein (IV; intravenous) every 2 weeks.
Other Name: RC48, RC48-ADC

Drug: pembrolizumab
Given by IV on Day 1 of each 6-week cycle.
Other Name: Keytruda
Experimental: Cohort C - Randomized monotherapy
Disitamab vedotin monotherapy
 Drug: disitamab vedotin
Given into the vein (IV; intravenous) every 2 weeks.
Other Name: RC48, RC48-ADC


Outcome Measures
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Primary Outcome Measures :
  1. Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR) [ Time Frame: Duration of treatment; approximately 2 years ]
    The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1


Secondary Outcome Measures :
  1. cORR per RECIST v1.1 by investigator assessment [ Time Frame: Duration of treatment; approximately 2 years ]
    The proportion of participants with confirmed CR or PR according to RECIST v1.1

  2. Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR [ Time Frame: From start of treatment to completion of response assessment; approximately 2 years ]
    The time from first documentation of objective tumor response (confirmed CR or PR) to the first documentation of tumor progression per RECIST v1.1 or death due to any cause.

  3. Confirmed DOR per RECIST v1.1 by investigator assessment [ Time Frame: From start of treatment to completion of response assessment; approximately 2 years ]
    The time from first documentation of objective tumor response (confirmed CR or PR) to the first documentation of tumor progression per RECIST v1.1 or death due to any cause.

  4. Progression-free survival (PFS) per RECIST v1.1 by BICR [ Time Frame: From start of treatment to completion of response assessment; approximately 2 years ]
    The time from the start of study treatment or randomization (if applicable) to the first documentation of disease progression per RECIST v1.1 or death due to any cause.

  5. PFS per RECIST v1.1 by investigator assessment [ Time Frame: From start of treatment to completion of response assessment; approximately 2 years ]
    The time from the start of study treatment or randomization (if applicable) to the first documentation of disease progression per RECIST v1.1 or death due to any cause.

  6. Disease control rate (DCR) per RECIST v1.1 by BICR [ Time Frame: From start of treatment to completion of response assessment; approximately 2 years ]
    The proportion of participants who have achieved objective response (confirmed CR or PR as per RECIST v1.1 criteria) or stable disease (SD) lasting at least 5 weeks.

  7. DCR per RECIST v1.1 by investigator [ Time Frame: From start of treatment to completion of response assessment; approximately 2 years ]
    The proportion of participants who have achieved objective response (confirmed CR or PR as per RECIST v 1.1 criteria) or SD lasting at least 5 weeks.

  8. Overall survival (OS) [ Time Frame: Duration of study; approximately 3 years ]
    The time from start of study treatment or randomization (if applicable) to the date of death due to any cause.

  9. Incidence of adverse events (AEs) [ Time Frame: Approximately 2 years ]
    Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

  10. Incidence of dose alterations [ Time Frame: Approximately 2 years ]
    To be summarized using descriptive statistics.

  11. Incidence of laboratory abnormalities [ Time Frame: Approximately 2 years ]
    To be summarized using descriptive statistics.

  12. Incidence of electrocardiogram (ECG) abnormalities [ Time Frame: Approximately 2 years ]
  13. Change from baseline left ventricular ejection fraction (LVEF) [ Time Frame: Approximately 2 years ]
  14. Pharmacokinetic (PK) parameter - Area under the curve (AUC) [ Time Frame: Through 30-37 days following the last dose of DV; up to approximately 2 years ]
    To be summarized using descriptive statistics.

  15. PK parameter - Maximum concentration (Cmax) [ Time Frame: Through 30-37 days following the last dose of DV; up to approximately 2 years ]
    To be summarized using descriptive statistics.

  16. PK parameter - Time to maximum concentration (Tmax) [ Time Frame: Through 30-37 days following the last dose of DV; up to approximately 2 years ]
    To be summarized using descriptive statistics.

  17. PK parameter - Trough concentration (Ctrough) [ Time Frame: Through 30-37 days following the last dose of DV; up to approximately 2 years ]
    To be summarized using descriptive statistics.

  18. Incidence of anti-drug antibodies (ADAs) [ Time Frame: Through 30-37 days following the last dose of DV; up to approximately 2 years ]
    To be summarized using descriptive statistics.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Expected survival ≥12 weeks
  • Histologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra

  • Cohorts A and B: Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy

    • Neoadjuvant or adjuvant systemic therapy, with progression within 12 months of completing last dose of 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 is allowed

  • Cohort C: No prior systemic therapy for LA/mUC

    • Neoadjuvant or adjuvant therapy, including PD-(L1) inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy
  • Cohorts A and B only: Radiographically documented disease progression during or after the most recent line of therapy for LA/mUC
  • At least one measurable lesion by investigator assessment based on RECIST version 1.1.
  • Cohort C only: Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation
  • Participants must be able to provide archived tumor tissue prior to treatment initiation. If archival tissue is not available, a baseline biopsy is required within 28 days of Cycle 1 Day 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:

    • Cohorts A and B: ECOG of 0 or 1
    • Cohort C: ECOG of 0, 1, or 2

Exclusion Criteria:

  • Known hypersensitivity to disitamab vedotin, pembrolizumab (in Cohort C), or any of their components
  • Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study
  • 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

  • Other malignant tumors within 3 years of study treatment, except for:

    • Prostate cancer treated with definitive intent (surgically or with radiation therapy) ≥ 1 year prior to treatment initiation is acceptable
    • Malignancies that can be cured after treatment

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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04879329


Contacts
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Contact: Seagen Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
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Sponsors and Collaborators
Seagen Inc.
RemeGen Co., Ltd.
Merck Sharp & Dohme LLC
Investigators
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Study Director: Kevin Sokolowski, MD Seagen Inc.
More Information
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Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT04879329    
Other Study ID Numbers: RC48G001
KEYNOTE-D78 ( Other Identifier: Merck Sharp & Dohme LLC )
First Posted: May 10, 2021    Key Record Dates
Last Update Posted: January 5, 2023
Last Verified: January 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seagen Inc.:
Urothelial Cancer
Bladder Cancer
HER2 Mutations
 HER2 Overexpression
HER2 Amplification
Seattle Genetics
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
 Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents