Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer

Breast Cancer Clinical Trial

Official title:

A Phase 1b, Multicenter, Two-Part, Open-Label Study of Trastuzumab Deruxtecan, an Anti-Human Epidermal Growth Factor Receptor-2 (HER2)-Antibody Drug Conjugate (ADC), in Combination With Nivolumab, an Anti-PD-1 Antibody, for Subjects With HER2-expressing Advanced Breast and Urothelial Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03523572
• Other study ID #: DS8201-A-U105
• Secondary ID: 2018-000371-32
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 20, 2018
• Est. completion date: July 2022

Study information

• Verified date: August 2021
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study of trastuzumab deruxtecan, which was approved by the FDA (in December 2019) for the treatment of HER2-positive unresectable or metastatic breast cancer following two or more prior anti-HER2 based regimens.

Participants will receive this study drug along with a cancer drug, an immune checkpoint inhibitor, anti-PD1, called nivolumab.

The study will be done in two parts:

• Part 1 is to identify the recommended dose to use for treatment.

• Part 2 is to find out how well the combination works, and how safe and tolerable it is.

Description:

The purpose of this phase 1b (Part 1, Part 2) study is to assess the combination of a test drug (trastuzumab deruxtecan) with nivolumab in participants with HER2-expressing breast and urothelial cancer who had disease progression during or after prior therapies, did not respond to standard therapies, or for whom no standard therapy is available.

The study will be performed in 2 parts.

• Part 1 is to test different doses of trastuzumab deruxtecan when given along with a fixed dose of nivolumab, and establish the most effective and the maximum/recommended tolerated dose, when used in combination with nivolumab

• Part 2 is to assess the efficacy and safety of this dose combination.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 99
• Est. completion date: July 2022
• Est. primary completion date: July 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Is the age of majority (adulthood) in their country

2. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1

3. Has pathologically documented breast cancer or urothelial cancer that is unresectable or metastatic, and refractory to or intolerant of existing therapy(ies) known to provide clinical benefit, and as specified in each study cohort

4. Has an adequate archival tumor sample available for the central laboratory to determine eligibility to participate

5. Has at least 1 measurable lesion per RECIST version 1.1

6. Has cardiac, bone marrow, kidney, liver, blood and clotting test results required per protocol

7. Has had an adequate washout period before enrollment since previous surgery and other treatment

8. If reproduction is possible, agrees to use protocol-defined methods of contraception (or completely abstain from heterosexual intercourse) from screening to at least 7 months for females and males after the last dose of study drug

9. Agrees to avoid harvesting sperm or ova for any reason from screening to at least 7 months for females and males after the last dose of study drug

10. Has a life expectancy of at least 3 months

Exclusion Criteria:

1. Has received prior treatment with nivolumab or trastuzumab deruxtecan

2. Has medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association classes II-IV). Troponin levels above upper limit of normal (ULN) at screening (as defined by the manufacturer) and without any MI-related symptoms should have a cardiologic consultation before enrollment to rule out MI.

3. Has a corrected QT interval by Fredericia (QTcF) prolongation to > 470 ms (females) or > 450 ms (males) based on an average of the screening triplicate 12-lead electrocardiogram

4. Has history of non-infectious interstitial lung disease (ILD/pneumonitis) (that required steroids), has ILD/pneumonitis currently, or it cannot be ruled out by imaging at screening

5. Has a condition (other than active autoimmune disease) that requires systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of starting study treatment

6. Is pregnant or breastfeeding, or planning to become pregnant

7. Is suspected to have certain other protocol-defined diseases based on past medical history, physical exam, blood tests, eye test and imaging at screening period

8. Has received a live vaccine within 30 days before the first dose of study drug

9. Is related to the investigator or another employee of the sponsor or the study site

10. Is pregnant, breastfeeding, or planning to become pregnant

11. Has or had any disease, psychiatric or medical condition, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:

1. safety or well-being of the participant or offspring

2. safety of study staff

3. analysis of results

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Drug:
• Trastuzumab deruxtecan
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
• Nivolumab
Nivolumab is an aqueous solution formulated at 10 mg/mL to be administered at a flat dose of 360 mg IV over 30 minutes. Protocol-defined thyroid testing is required while taking nivolumab.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	AZ Groeninge	Kortrijk	West-Vlaanderen
Belgium	GZA Hospital Campus Sint-Augustinus	Wilrijk
France	Institut de Cancerologie de L'Ouest	Angers
France	Centre Georges Francois Leclerc	Dijon
France	ICO Rene Gauducheau	Saint-Herblain
Germany	Charite Campus Benjamin Franklin	Berlin	Brandenburg
Germany	University Cancer Center	Dresden	Sachsen
Germany	University Hospital Frankfurt	Frankfurt	Hessen
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera Universitaria Senese U.O.C. Immunoterapia Oncologica	Siena
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital Gregorio Maranon Madrid Spain	Madrid
Spain	Hospital Universitario Ramon y Cajal Madrid	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	START Madrid CIOCC	Madrid
United Kingdom	Sarah Cannon Research Institute UK	London	England
United Kingdom	Royal Marsden Hospital (Surrey)	London Borough of Sutton
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Levine Cancer Institute Carolinas Healthcare System	Charlotte	North Carolina
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Miami Hospital & Clinics/Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Tennessee Oncology - Sara Cannon Research Institute	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCLA - Medical Center	Santa Monica	California
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.	AstraZeneca, Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of participants with dose-limiting toxicity at each dose level	Categories: Low Dose, High Dose	2 cycles (within 2 months; each cycle is 21 days)
Primary	Part 2: Dose expansion - Objective response rate (ORR) as assessed by Central Imaging Review	ORR is defined as the percentage of participants with tumor size reduction of a predefined amount and for a minimum time period. ORR includes partial response (PR) and complete response (CR). ORR will be assessed by Central Imaging Review based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	6 months after the last participant is enrolled, or when 80% of participants have experienced disease progression or discontinued study treatment, whichever occurs first (within 24 months)
Secondary	Duration of Response (DoR)		within 24 months
Secondary	Disease Control Rate (DCR)		within 24 months
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from randomization until objective tumor progression or death, whichever occurs first.	within 24 months
Secondary	Time to Response based on central review		within 24 months
Secondary	Overall Survival (OS)	Overall survival is defined as the time from randomization until death from any cause and is measured in the intent-to-treat population.	within 24 months
Secondary	ORR	ORR, as assessed by the investigator based on RECIST Version 1.1.	within 24 months
Secondary	Number of participants with treatment emergent adverse events (TEAEs) during the trial	Total number of participants in the safety analysis set with TEAEs collected during the trial (including follow-up periods), for inclusion in the database	at the time of final database lock (anticipated within three years)