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A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer

NCT04556773

Description:

DESTINY-Breast 08 will investigate the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies in patients with Metastatic HER2-low Advanced or Metastatic Breast Cancer

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer
  • Official Title: A Phase 1b Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With Metastatic HER2-low Breast Cancer (DESTINY-Breast08)

Clinical Trial IDs

  • ORG STUDY ID: D967JC00002
  • NCT ID: NCT04556773

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
Trastuzumab deruxtecanDS-8201a, T-DXdModule 1: T-DXd + capecitabine
DurvalumabMEDI4736Module 2: T-DXd + durvalumab + paclitaxel
PaclitaxelModule 2: T-DXd + durvalumab + paclitaxel
CapivasertibAZD5363Module 3: T-DXd + capivasertib
AnastrozoleModule 4: T-DXd + anastrozole
FulvestrantModule 5: T-DXd + fulvestrant
CapecitabineModule 1: T-DXd + capecitabine

Purpose

DESTINY-Breast 08 will investigate the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies in patients with Metastatic HER2-low Advanced or Metastatic Breast Cancer

Detailed Description

      This study is modular in design allowing assessment of the safety, tolerability, PK and
      preliminary anti-tumour activity of T-DXd in combination with other therapies.
      Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose
      expansion phase (Part 2); the Part 2 dose-expansion phase will use the RP2D determined in
      Part 1.

      The target population of interest in this study is patients with HER2-low (IHC 1+ or IHC
      2+/ISH -) (as per ASCO/CAP 2018 guidelines) advanced/MBC. Part 1 of each module will enroll
      patients with locally confirmed HER2-low advanced/MBC in second-line or later (≥ 2L) settings

      Part 2 of each module will enroll patients with HER2-low MBC who have either not received
      prior treatment, or received only 1 prior treatment (depending on the module-specific
      exclusion criteria) for advanced/metastatic disease
    

Trial Arms

NameTypeDescriptionInterventions
Module 1: T-DXd + capecitabineExperimentalT-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use
  • Trastuzumab deruxtecan
  • Capecitabine
Module 2: T-DXd + durvalumab + paclitaxelExperimentalT-DXd: 5.4 mg/kg Q3W, intravenous use Durvalumab: 1120 mg Q3W, intravenous use Paclitaxel: 80 mg/m2 QW in 3-week cycles, intravenous use
  • Trastuzumab deruxtecan
  • Durvalumab
  • Paclitaxel
Module 3: T-DXd + capivasertibExperimentalT-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use
  • Trastuzumab deruxtecan
  • Capivasertib
Module 4: T-DXd + anastrozoleExperimentalT-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral
  • Trastuzumab deruxtecan
  • Anastrozole
Module 5: T-DXd + fulvestrantExperimentalT-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use
  • Trastuzumab deruxtecan
  • Fulvestrant

Eligibility Criteria

        Key Inclusion Criteria:

          -  Patients must be at least 18 years of age

          -  Male or female patients who have pathologically documented breast cancer that:

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

               2. Is documented as HR+ (either ER and/or PgR positive [ER or PgR ≥1%]) or ER and
                  PgR negative (ER and PgR <1%) per ASCO/CAP guidelines in the metastatic setting

          -  Patient must have adequate tumor sample for biomarker assessment

          -  ECOG Performance Status of 0 or 1

        For patients with HR+ disease:

        Part 1: At least 1 prior treatment line of ET with or without a targeted therapy (such as
        CDK4/6, mTOR or PI3-K inhibitors), and at least 1 prior line of chemotherapy for MBC are
        required.

        Part 2: Only 1 prior treatment line of ET with or without a targeted therapy (such as
        CDK4/6, mTOR or PI3-K inhibitors) for MBC is allowed. No prior chemotherapy in the
        metastatic setting is allowed. Note there are no patients with HR+ disease in Part 2 of
        Modules 2 and 3.

        For patients with HR- disease:

        Part 1: At least 1 prior line of chemotherapy for MBC is required. Note there are no
        patients with HR- disease in Part 1 of Modules 4 and 5.

        Part 2: For Module 2, no prior lines of therapy for MBC are allowed, and for Modules 1 and
        3, only 1 prior line of chemotherapy for MBC is allowed. Note there are no patients with
        HR- disease in Part 2 of Modules 4 and 5.

        Key Exclusion Criteria:

          -  Uncontrolled intercurrent illness

          -  Uncontrolled or siginificant cardiovascular disease

          -  History of (non-infectious) ILD/pneumonitis that required steroids, has current
             ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at
             screening.

          -  Lung-specific intercurrent clinically significant illnesses

          -  Has spinal cord compression or clinically active central nervous system metastases

          -  Active primary immunodeficiency

          -  Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals

          -  Prior treatment with ADC that comprises of an exatecan derivative that is a
             topoisomerase I inhibitor.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of adverse events (AEs)- Part 1
Time Frame:Up to follow-up period, approximately 24 months
Safety Issue:
Description:Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)- Part 2
Time Frame:Until progression, assessed up to approximately 24 months
Safety Issue:
Description:ORR defined as the proportion of patients who have a confirmed CR or PR, as determined by the investigator at local site per RECIST 1.1
Measure:Progression Free Survival (PFS)- Part 2
Time Frame:Until progression or death, assessed up to approximately 24 months
Safety Issue:
Description:PFS defined as time from the date of first dose until the date of progression as determined by the investigator at local site per RECIST 1.1, or death due to any cause
Measure:Duration of Response (DoR)- Part 2
Time Frame:Until progression or death, assessed up to approximately 24 months
Safety Issue:
Description:DoR defined as time from the date of first documented response (which is subsequently confirmed) until the date of documented progression or death in the absence of disease progression
Measure:Overall Survival (OS)- Part 2
Time Frame:Until death, assessed up to approximately 24 months
Safety Issue:
Description:OS defined as time from the date of first dose until the date of death by any cause
Measure:Serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a
Time Frame:While on study drug up to study completion, approximately 24 months
Safety Issue:
Description:Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
Measure:Immunogenicity of trastuzumab deruxtecan
Time Frame:Up to follow-up period, approximately 24 months
Safety Issue:
Description:Percentage of patients who develop ADA for trastuzumab deruxtecan
Measure:Serum Concentration of durvalumab
Time Frame:While on study drug up to study completion, approximately 24 months
Safety Issue:
Description:Determination of durvalumab concentration in serum at different time points after administration
Measure:Immunogenicity of durvalumab
Time Frame:Up to follow-up period, approximately 24 months
Safety Issue:
Description:Percentage of patients who develop ADAs for durvalumab

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Breast Cancer
  • HER2-negative
  • HER2-low
  • Trastuzumab Deruxtecan
  • T-DXd
  • DS-8201a
  • DESTINY-Breast08
  • Anti-HER2 Antibody Drug Conjugate (ADC)
  • Triple-negative breast cancer (TNBC)

Last Updated

September 15, 2020