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

Sponsor

Seagen Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04879329

Collaborator

RemeGen Co., Ltd. (Industry), Merck Sharp & Dohme LLC (Industry)

270

Enrollment

Locations

Arms

46.9

Anticipated Duration (Months)

67.5

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

Anticipated 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

Anticipated Primary Completion Date :

Oct 31, 2024

Anticipated Study Completion Date :

Mar 31, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR) [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

cORR per RECIST v1.1 by investigator assessment [Duration of treatment; approximately 2 years]
The proportion of participants with confirmed CR or PR according to RECIST v1.1
Confirmed Duration of Response (DOR) per RECIST v1.1 by BICR [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.
Confirmed DOR per RECIST v1.1 by investigator assessment [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.
Progression-free survival (PFS) per RECIST v1.1 by BICR [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.
PFS per RECIST v1.1 by investigator assessment [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.
Disease control rate (DCR) per RECIST v1.1 by BICR [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.
DCR per RECIST v1.1 by investigator [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.
Overall survival (OS) [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.
Incidence of adverse events (AEs) [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.
Incidence of dose alterations [Approximately 2 years]
To be summarized using descriptive statistics.
Incidence of laboratory abnormalities [Approximately 2 years]
To be summarized using descriptive statistics.
Incidence of electrocardiogram (ECG) abnormalities [Approximately 2 years]
Change from baseline left ventricular ejection fraction (LVEF) [Approximately 2 years]
Pharmacokinetic (PK) parameter - Area under the curve (AUC) [Through 30-37 days following the last dose of DV; up to approximately 2 years]
To be summarized using descriptive statistics.
PK parameter - Maximum concentration (Cmax) [Through 30-37 days following the last dose of DV; up to approximately 2 years]
To be summarized using descriptive statistics.
PK parameter - Time to maximum concentration (Tmax) [Through 30-37 days following the last dose of DV; up to approximately 2 years]
To be summarized using descriptive statistics.
PK parameter - Trough concentration (Ctrough) [Through 30-37 days following the last dose of DV; up to approximately 2 years]
To be summarized using descriptive statistics.
Incidence of anti-drug antibodies (ADAs) [Through 30-37 days following the last dose of DV; up to approximately 2 years]
To be summarized using descriptive statistics.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Cancer and Hematology Centers of Western Michigan / Spectrum Health Butterworth Campus	Grand Rapids	Michigan	United States	49503
2	Mount Sinai - Tisch Cancer Institute	New York	New York	United States	10029
3	University of Tennessee	Knoxville	Tennessee	United States	37920
4	Inova Health Care Services	Falls Church	Virginia	United States	22042