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Brief Title: Disitamab Vedotin in Subjects With HER2 Expressing Urothelial Carcinoma

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

INTRODUCTION

  • Org Study ID: RC48G001
  • Secondary ID: KEYNOTE-D78
  • NTC ID: NCT04879329
  • Sponsor: Seagen Inc.

DESCRIPTION

To read more about what this clinical trial is about please click this link:

RC48G001_PFM_PatientTrialCard_US_ENG_V1.0_30Aug2022_USM_DV_2022_0018

 

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.

  • Overall Status
    Recruiting
  • Start Date
    May 3, 2022
  • Phase
    Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: 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 A, B, and C)

Primary Outcome 1 - Timeframe: Duration of treatment; approximately 2 years

Primary Outcome 2 - Measure: Incidence of adverse events (AEs) (Cohorts D and E)

Primary Outcome 2 - Timeframe: Approximately 2 years

Primary Outcome 3 - Measure: Incidence of dose alterations (Cohorts D and E)

Primary Outcome 3 - Timeframe: Approximately 2 years

Primary Outcome 4 - Measure: Incidence of laboratory abnormalities (Cohorts D and E)

Primary Outcome 4 - Timeframe: Approximately 2 years

Primary Outcome 5 - Measure: Incidence of electrocardiogram (ECG) abnormalities (Cohorts D and E)

Primary Outcome 5 - Timeframe: Approximately 2 years

Primary Outcome 6 - Measure: Change from baseline of left ventricular ejection fraction (LVEF) (Cohorts D and E)

Primary Outcome 6 - Timeframe: Approximately 2 years

Primary Outcome 7 - Measure: Pharmacokinetic (PK) parameter - Area under the curve (AUC) (Cohorts D and E)

Primary Outcome 7 - Timeframe: Through 30-37 days following the last dose of DV; up to approximately 2 years

Primary Outcome 8 - Measure: PK parameter - Maximum concentration (Cmax) (Cohorts D and E)

Primary Outcome 8 - Timeframe: Through 30-37 days following the last dose of DV; up to approximately 2 years

Primary Outcome 9 - Measure: PK parameter - Time to maximum concentration (Tmax) (Cohorts D and E)

Primary Outcome 9 - Timeframe: Through 30-37 days following the last dose of DV; up to approximately 2 years

Primary Outcome 10 - Measure: PK parameter - Trough concentration (Ctrough) (Cohorts D and E)

Primary Outcome 10 - Timeframe: Through 30-37 days following the last dose of DV; up to approximately 2 years

CONDITION

  • Urothelial Carcinoma

ELIGIBILITY

Inclusion Criteria:
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:
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
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:
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)

- 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Kevin Sokolowski, MD

Role: Study Director

Affiliation: Seagen Inc.

Overall Contact

Name: Kevin Sokolowski, MD

Phone: 866-333-7436

Email: clinicaltrials@seagen.com

LOCATION

Facility Status Contact
Facility: Banner MD Anderson Cancer Center
Gilbert, Arizona 85234
United States
Status: Recruiting Contact: Principal Investigator
Isaac Bowman

Facility: UCLA Medical Center / David Geffen School of Medicine
Los Angeles, California 90095
United States
Status: Recruiting Contact: Principal Investigator
Alexandra Drakaki

Facility: University of California Irvine Medical Center
Orange, California 92868
United States
Status: Recruiting Contact: Principal Investigator
Nataliya Mar

Facility: University of California at San Francisco
San Francisco, California 94158
United States
Status: Recruiting Contact: Principal Investigator
Vadim Koshkin

Facility: University of Colorado Health Memorial Hospital
Colorado Springs, Colorado 80909
United States
Status: Recruiting Contact: Principal Investigator
Rubens Chang

Facility: Florida Cancer Specialists - South Region
Fort Myers, Florida 33901
United States
Status: Recruiting Contact: Principal Investigator
Amir Harandi

Facility: Florida Cancer Specialists - Panhandle
Tallahassee, Florida 32308
United States
Status: Recruiting Contact: Principal Investigator
Pareshkumar Patel

Facility: Florida Cancer Specialists - East West Palm Beach, FL (SCRI)
West Palm Beach, Florida 33401
United States
Status: Recruiting Contact: Principal Investigator
Barry Berman

Facility: Northwest Georgia Oncology Centers, P.C.
Marietta, Georgia 30060
United States
Status: Recruiting Contact: Principal Investigator
Steve McCune

Facility: University of Chicago Medical Center
Chicago, Illinois 60637
United States
Status: Recruiting Contact: Principal Investigator
Peter O'Donnell

Facility: Karmanos Cancer Institute / Wayne State University
Detroit, Michigan 48226
United States
Status: Recruiting Contact: Principal Investigator
Elisabeth Heath

Facility: Cancer and Hematology Centers of Western Michigan / Spectrum Health Butterworth Campus
Grand Rapids, Michigan 49503
United States
Status: Recruiting Contact: Principal Investigator
Eric Batts

Facility: Mount Sinai - Tisch Cancer Institute
New York, New York 10029
United States
Status: Recruiting Contact: Principal Investigator
Matthew Galsky

Facility: Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Status: Recruiting Contact: Principal Investigator
Gopakumar Iyer

Facility: Levine Cancer Institute
Charlotte, North Carolina 90404
United States
Status: Recruiting Contact: Principal Investigator
Jason Brown, MD

Facility: Case Western Reserve University / University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106
United States
Status: Recruiting Contact: Principal Investigator
Saikrishna Gadde

Facility: University of Tennessee
Knoxville, Tennessee 37920
United States
Status: Recruiting Contact: Principal Investigator
Matthew Campbell

Facility: MD Anderson Cancer Center / University of Texas
Houston, Texas 77030-4095
United States
Status: Recruiting Contact: Principal Investigator
Jeanny Aragon-Ching

Facility: Inova Health Care Services
Falls Church, Virginia 22042
United States
Status: Recruiting Contact: Principal Investigator
Evan Yu

Facility: Seattle Cancer Care Alliance / University of Washington
Seattle, Washington 98109
United States
Status: Recruiting Contact: Principal Investigator
Mirta Varela

Facility: Centro de Oncologia e Investigacion de Buenos Aires (COIBA)
Berazategui, Other B1884BBF
Argentina
Status: Recruiting Contact: Principal Investigator
Hernan Cutuli

Facility: Hospital Sirio Libanes
Caba, Other 1425
Argentina
Status: Recruiting Contact: Principal Investigator
Juan Pablo Sade

Facility: Instituto Alexander Fleming
Ciudad Autonoma Buenos Aires, Other C1426ANZ
Argentina
Status: Recruiting Contact: Principal Investigator
Sanjeev Sewak

Facility: Peninsula and South East Oncology
Frankston, Other 3199
Australia
Status: Recruiting Contact: Principal Investigator
Niara Oliveira

Facility: Mater Cancer Care Centre
South Brisbane, Other 4101
Australia
Status: Recruiting Contact: Principal Investigator
Laurence Krieger, MD

Facility: Royal North Shore Hospital
St Leonards, Other 2065
Australia
Status: Recruiting Contact: Principal Investigator
Bernhard Eigl

Facility: British Columbia Cancer Agency - Vancouver Centre
Vancouver, British Columbia V5Z4E6
Canada
Status: Recruiting Contact: Principal Investigator
April Rose, MD, PhD

Facility: Jewish General Hospital
Montreal, Quebec H3T 1E2
Canada
Status: Recruiting Contact: Principal Investigator
Michel Pavic

Facility: Centre hospitalier universitaire de Sherbrooke (CHUS)
Sherbrooke, Quebec J1H 5N4
Canada
Status: Recruiting Contact: Principal Investigator
Pamela Salman

Facility: Instituto Oncologico Fundacion Arturo Lopez Perez (FALP)
Santiago, Other Providencia
Chile
Status: Recruiting Contact: Principal Investigator
Avivit Pe'er

Facility: Rambam Health Corp.
Haifa, Other 3109601
Israel
Status: Recruiting Contact: Principal Investigator
Michal Sarfaty

Facility: Sheba Medical Center
Ramat Gan, Other 52621
Israel
Status: Recruiting Contact: Principal Investigator
Thomas Powles

Facility: Barts Health NHS Trust Saint Bartholomews Hospital
London, Other EC1A 7BE
United Kingdom
Status: Recruiting Contact: N/A