Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer

Brief Title

Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer

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

Brief 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.
    

Detailed 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.
    

Study Phase

Phase 1

Study Type

Interventional

Primary Outcome

Part 1: Number of participants with dose-limiting toxicity at each dose level

Secondary Outcome

 Duration of Response (DoR)

Condition

Breast Cancer

Intervention

Trastuzumab deruxtecan

Study Arms / Comparison Groups

 Dose Escalation

Description:  Part 1 will enroll participants meeting the eligibility criteria set up for any of the 4 cohorts of Part 2 specified below using a 3 + 3 + 3 design. Escalating/de-escalating doses of trastuzumab deruxtecan in combination with a flat dose of nivolumab will be administered on Day 1 of each 21-day cycle.
The recommended dose for expansion (RDE) will be calculated using data collected from this population in the first two cycles. These participants may continue to receive study treatment in subsequent cycles.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

99

Start Date

June 20, 2018

Completion Date

July 2022

Primary Completion Date

July 22, 2021

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Global Team Leader, , 

Location Countries

Belgium

Location Countries

Belgium

NCT ID

NCT03523572

Organization ID

DS8201-A-U105

Secondary IDs

2018-000371-32

Responsible Party

Sponsor

Study Sponsor

Daiichi Sankyo, Inc.

Collaborators

 Bristol-Myers Squibb

Study Sponsor

Global Team Leader, Study Director, Daiichi Sankyo, Inc.

Verification Date

August 2021