Clinical Trials /

Trastuzumab Deruxtecan (DS-8201a) With Nivolumab in Advanced Breast and Urothelial Cancer

NCT03523572

Description:

This is a study of DS-8201a, which is an experimental drug not approved yet by the FDA. Participants will receive this study drug along with a cancer drug that is already being used, 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.

Related Conditions:
  • Breast Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trastuzumab Deruxtecan (DS-8201a) With Nivolumab in Advanced Breast and Urothelial Cancer
  • Official Title: A Phase 1b, Multicenter, Two-Part, Open-Label Study of DS-8201a, 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 IDs

  • ORG STUDY ID: DS8201-A-U105
  • SECONDARY ID: 2018-000371-32
  • NCT ID: NCT03523572

Conditions

  • Breast Cancer
  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
Trastuzumab deruxtecan (DS-8201a)Experimental productDose Escalation
NivolumabOpdivoDose Escalation

Purpose

The purpose of this phase 1b study is to test the combination of an experimental drug known as DS-8201a given along with Nivolumab (a marketed drug) 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 look at different doses of DS-8201a when given along with a fixed dose of nivolumab, and establish the most effective and safe dose (maximum/recommended tolerated dose) when used in combination with nivolumab. - Part 2 is to understand the positive or negative effects of this dose combination on the participant's body and disease. The study will also determine the pharmacokinetics of DS-8201a when administered with nivolumab.

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalPart 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 doses of trastuzumab deruxtecan (DS-8201a) in combination with nivolumab will be assessed. DS-8201a and nivolumab will be administered on Day 1 of each 21-day cycle.
  • Trastuzumab deruxtecan (DS-8201a)
  • Nivolumab
Dose Expansion - Cohort 1ExperimentalCohort 1 (n=30): Advanced HER2-positive breast cancer [as defined by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines 2013] participants who have previously received ado-trastuzumab emtansine (T-DM1) with documented progression. Participants will receive the Part 1 recommended dose of trastuzumab deruxtecan (DS-8201a) and the same dose of nivolumab as in Part 1.
  • Trastuzumab deruxtecan (DS-8201a)
  • Nivolumab
Dose Expansion - Cohort 2ExperimentalCohort 2 (n=15): Advanced HER2 low-expressing breast cancer (HER2 IHC 1+ or IHC 2+/ISH-) participants who have exhausted treatments that can confer any clinically meaningful benefit (eg, other therapies such as hormonal therapy for patients who are hormone receptor positive). Participants will receive the Part 1 recommended dose of trastuzumab deruxtecan (DS-8201a) and the same dose of nivolumab as in Part 1.
  • Trastuzumab deruxtecan (DS-8201a)
  • Nivolumab
Dose Expansion - Cohort 3ExperimentalCohort 3 (n=30): Advanced HER2 high-expressing urothelial cancer (HER2 IHC 2+ or IHC 3+) participants who received prior platinum-based therapy with documented progression. Participants will receive the Part 1 recommended dose of trastuzumab deruxtecan (DS-8201a) and the same dose of nivolumab as in Part 1.
  • Trastuzumab deruxtecan (DS-8201a)
  • Nivolumab
Dose Expansion - Cohort 4ExperimentalCohort 4 (n=15): Advanced HER2 low-expressing urothelial cancer (HER2 IHC 1+) participants who have received prior platinum-based therapy with documented progression. Participants will receive the Part 1 recommended dose of trastuzumab deruxtecan (DS-8201a) and the same dose of nivolumab as in Part 1.
  • Trastuzumab deruxtecan (DS-8201a)
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Is the age of majority in their country

          -  Has histologically confirmed unresectable or metastatic breast or bladder cancer. The
             cancer is refractory and progressed after the last treatment

          -  Has at least 1 measurable lesion assessed by the investigator based on Response
             Evaluation Criteria in Solid Tumors (RECIST) version 1.1

          -  Meets the HER2 status in tumor tissue sample as confirmed by the central laboratory

          -  Is willing and able to provide an adequate archival tumor sample or is willing to
             undergo a tissue biopsy after the completion of the most recent treatment regimen

          -  Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1

          -  Demonstrates adequate organ functions: Required cardiac, bone marrow, kidney, liver
             and blood clotting functions as per protocol

          -  Has adequate washout period for previous surgery and other treatment before
             registration

          -  Agrees to use highly effective method of contraception starting with the first dose of
             study therapy through 7 months (for male) and 5 months (for female) after the last
             dose of study drug

          -  If a female of childbearing potential, has a negative urine or serum pregnancy within
             72 hours prior to receiving the first dose of study medication. If the urine test is
             positive or cannot be confirmed as negative, a serum pregnancy test will be required.

        Exclusion Criteria:

          -  Was previously treated with HER2-targeted therapy for HER2-positive breast cancer

          -  Was previously treated with medications such as anti-Programmed Death 1 PD-1 (or
             anti-PD-L1) or anti-Programmed Death Ligand 2 (anti-PD-L2), or anti-CTLA-4 antibody,
             or any other antibody or drug that specifically targets T-cell co-stimulation or
             checkpoint pathways.

          -  Has medical history of myocardial infarction, symptomatic congestive heart failure
             (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia

          -  Has a corrected QT (QTc) interval prolongation to > 450 millisecond (ms) in males and
             > 470 ms in females

          -  Has a medical history of clinically significant lung disease such as non-infectious
             interstitial lung disease or pneumonitis and require steroid treatment

          -  Requires treatment with either corticosteroids (>10 mg daily prednisone equivalent) or
             other immune suppression medications within 14 days of start of study treatment

          -  Is pregnant or breastfeeding, or planning to become pregnant

          -  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

          -  Has history of any disease, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose-limiting toxicity at each dose level
Time Frame:2 cycles (within 2 months)
Safety Issue:
Description:Categories: Low Dose, Medium Dose, High Dose

Secondary Outcome Measures

Measure:Duration of Response (DoR)
Time Frame:within 24 months
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:within 24 months
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:within 24 months
Safety Issue:
Description:
Measure:Time to Response based on central review
Time Frame:within 24 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:within 24 months
Safety Issue:
Description:
Measure:ORR
Time Frame:within 24 months
Safety Issue:
Description:ORR, as assessed by investigator and defined as the percentage of participants who achieved a confirmed response (CR or PR) during study treatment

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Human epidermal growth factor receptor-2
  • HER2
  • Refractory
  • Metastatic
  • Urothelial cancer
  • Breast Cancer

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