Clinical Trials /

DS-8201a Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]

NCT03734029

Description:

The reason for this trial is to compare DS-8201a to other treatments being used for HER2-low breast cancer that has spread to other parts of the body. DS-8201a is a new medicine for breast cancer that has not been approved yet by the Food and Drug Administration. It is made of a drug and an antibody. Each participant has a 2 out of 3 chance of receiving the new medicine.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: DS-8201a Compared to Treatment of Physician's Choice for Participants With a Certain Kind of Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]
  • Official Title: A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects

Clinical Trial IDs

  • ORG STUDY ID: DS8201-A-U303
  • SECONDARY ID: 2018-003069-33
  • NCT ID: NCT03734029

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Trastuzumab deruxtecan (DS-8201a)Experimental productDS-8201a
CapecitabineAnti-cancer drugPhysician's Choice
EribulinAnti-cancer DrugPhysician's Choice
GemcitabineAnti-cancer DrugPhysician's Choice
PaclitaxelAnti-cancer DrugPhysician's Choice
Nab-paclitaxelAnti-cancer DrugPhysician's Choice

Purpose

The reason for this trial is to compare DS-8201a to other treatments being used for breast cancer. DS-8201a is a new medicine for breast cancer that has not been approved yet by the Food and Drug Administration. It is made of a drug and an antibody. Each participant has a 2 out of 3 chance of receiving the new medicine.

Detailed Description

      This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and
      efficacy of DS8201a versus the physician's choice in HER2-low, unresectable and/or metastatic
      breast cancer subjects.

      The study is expected to enroll ~360 DS-8201a subjects and ~180 physician's choice subjects.
      After ~60 hormone receptor (HR)-negative subjects have been enrolled, further enrollment will
      be limited to only subjects who have HR-positive disease. After ~240 HR-positive subjects who
      have not had prior therapy with a cyclin-dependent kinase (CDK) 4/6 inhibitor have been
      enrolled, further enrollment will be limited to only subjects who have had prior therapy with
      a CDK4/6 inhibitor.

      The ~540 subjects will be randomized 2:1 to DS8201a versus the physician's choice of 1 of the
      following drugs:

        -  Capecitabine

        -  Eribulin

        -  Gemcitabine

        -  Paclitaxel

        -  Nab-paclitaxel

      There will be approximately 164 sites, including but not limited to, North America, Western
      Europe, and Asia.

      The Sponsor proposes to define a new HER2-low population in this trial including tumors with
      IHC 1+ and IHC 2+/ISH- HER2 expression.
    

Trial Arms

NameTypeDescriptionInterventions
DS-8201aExperimentalDS-8201a is administered as an intravenous (IV) infusion every 21 days (Q3W), initially for approximately 90 minutes, then, if there is no infusion-related reaction, for a minimum of 30 minutes thereafter.
  • Trastuzumab deruxtecan (DS-8201a)
Physician's ChoiceActive ComparatorPhysician's choice comparative therapy will be administered in accordance with the locally approved label. The physician's choice is predefined, prior to randomization, from the following options: Capecitabine Eribulin Gemcitabine Paclitaxel Nab-paclitaxel
  • Capecitabine
  • Eribulin
  • Gemcitabine
  • Paclitaxel
  • Nab-paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Is the age of majority in their country

          -  Has pathologically documented breast cancer that:

               1. Is unresectable or metastatic.

               2. Has a history of low HER2 expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or
                  untested).

               3. Is assessed by a central laboratory as low HER2 expression, defined as IHC
                  2+/ISH- or IHC 1+

               4. Is HR-positive or HR-negative. After ~60 HR-negative subjects are enrolled,
                  further enrollment will be limited to only subjects who are HR-positive (either
                  estrogen receptor positive or progesterone receptor positive per ASCO-CAP
                  guidelines).

               5. Is documented refractory to endocrine therapy, defined as having progressed on at
                  least 1 endocrine therapy and determined by the Investigator that subject would
                  no longer benefit from further treatment from endocrine therapy.

               6. If HR-positive, has or has not been treated with a CDK4/6 inhibitor. After ~240
                  HR-positive subjects have been enrolled who have not had prior therapy with a
                  CDK4/6 inhibitor, further enrollment of HR-positive subjects will be limited to
                  subjects who have had prior therapy with a CDK4/6 inhibitor.

               7. Has been treated with at least 1 and at most 2 prior lines of chemotherapy in the
                  metastatic setting. If recurrence occurred within 6 months of adjuvant
                  chemotherapy, adjuvant therapy would count as 1 line of chemotherapy.

               8. Was never previously HER2-positive (IHC 3+ or ISH+) on prior pathology testing
                  (per ASCO-CAP guidelines.)

               9. Was never previously treated with anti HER2 therapy.

          -  Has documented radiologic progression (during or after most recent treatment)

          -  Has an adequate archival tumor sample available for assessment of HER2 status by
             central laboratory (based on most recent available tumor tissue sample). If archival
             tissue is not available, a fresh biopsy is required.

          -  Has a recent tumor sample after the most recent treatment regimen or agree to undergo
             a tissue biopsy prior to randomization

          -  Has at least 1 measurable lesion based on computed tomography (CT) or magnetic
             resonance imaging (MRI), per modified Response Evaluation Criteria in Solid Tumors
             (mRECIST) version 1.1

          -  Has left ventricular ejection fraction (LVEF) ≥50%

          -  Has adequate renal function, defined as creatinine clearance ≥30 mL/min, as calculated
             using the CockcroftGault equation

          -  Has adequate hepatic function, defined as:

               1. Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤5 × upper limit
                  of normal (ULN)

               2. Total bilirubin ≤1.5 × ULN) if no liver metastases or <3 × ULN in the presence of
                  documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver
                  metastases at baseline

          -  If of reproductive/childbearing potential, agrees to follow instructions for method(s)
             of contraception

        Exclusion Criteria:

          -  Is ineligible for all 5 of the options in the physician's choice arm, either because
             of previously receiving treatment in the metastatic setting with the comparator, or
             having a contraindication to treatment

          -  Has medical history of myocardial infarction within 6 months before randomization

          -  Has history of symptomatic congestive heart failure (New York Heart Association Class
             II to IV)

          -  Has corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (male)
             based on average of Screening triplicate 12-lead electrocardiograms (ECGs)

          -  Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that
             required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis
             cannot be ruled out by imaging at Screening

          -  Has spinal cord compression or clinically active central nervous system metastases,
             defined as untreated and symptomatic, or requiring therapy with corticosteroids or
             anticonvulsants to control associated symptoms

        NOTE: Subjects with treated brain metastases that are no longer symptomatic and who require
        no treatment with corticosteroids or anticonvulsants may be included in the study if they
        have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have
        elapsed between the end of whole brain radiotherapy and study enrollment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR)
Time Frame:at approximately 3 years
Safety Issue:
Description:PFS based on BICR is defined as the time from the date of randomization to the earliest date of the first objective documentation of radiographic disease progression, assessed via BICR according to the modified response evaluation criteria in solid tumors (mRECIST) version 1.1, or death due to any cause. First dose at Cycle 1 Day 1 should occur within 7 days after the date the subject is randomized.

Secondary Outcome Measures

Measure:PFS based on Investigator Assessment
Time Frame:at approximately 3 years
Safety Issue:
Description:PFS based on Investigator Assessment is defined as the time from the date of randomization to the earliest date of the first clinical observation of disease progression or death due to any cause, assessed by BICR review using mRECIST version 1.1.
Measure:Overall Survival (OS)
Time Frame:at approximately 3 years
Safety Issue:
Description:OS is defined as the time from the date of randomization to the date of death for any cause, assessed by BICR review using mRECIST version 1.1.
Measure:Confirmed Objective Response Rate (ORR)
Time Frame:at approximately 3 years
Safety Issue:
Description:Confirmed ORR is defined as the sum of complete response (CR) rate and partial response (PR) rate, based on BICR and Investigator Assessment, and confirmed by a second assessment by BICR review using mRECIST version 1.1.
Measure:Duration of Response (DoR), based on BICR and Investigator assessment
Time Frame:at approximately 3 years
Safety Issue:
Description:DoR is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of disease progression, based on BICR and Investigator assessment, or death. Duration of response will be measured for responding subjects (PR or CR) only, and be assessed by BICR review using mRECIST version 1.1.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Anti-HER2-Antibody Drug Conjugate (ADC)
  • Unresectable or Metastatic
  • Human epidermal growth factor receptor 2 (HER2)-low
  • DESTINY - Breast 04

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