Clinical Trials /

A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer

NCT04538742

Description:

DESTINY-Breast07 will investigate the safety, tolerability, and anti-tumour activity of trastuzumab deruxtecan (T-DXd) in combination with other anti-cancer agents in patients with HER2-positive Metastatic Breast Cancer

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer
  • Official Title: A Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With HER2-positive Metastatic Breast Cancer (DESTINY-Breast07)

Clinical Trial IDs

  • ORG STUDY ID: D967JC00001
  • NCT ID: NCT04538742

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
Trastuzumab deruxtecanDS-8201a, T-DXdModule 0- T-DXd
DurvalumabMEDI4736Module 1- T-DXd and Durvalumab
PaclitaxelModule 3- T-DXd and Paclitaxel
PertuzumabModule 2- T-DXd and Pertuzumab
TucatinibONT-380Module 5 - T-DXd and Tucatanib

Purpose

DESTINY-Breast07 will investigate the safety, tolerability, and anti-tumour activity of trastuzumab deruxtecan (T-DXd) in combination with other anti-cancer agents in patients with HER2-positive Metastatic Breast Cancer

Detailed Description

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

      The target population of interest in this study is patients with HER2-positive (as per
      ASCO/CAP 2018 guidelines) advanced/MBC inclusive of patients with active and stable brain
      metastases. Part 1 of each module will enroll patients with locally assessed HER2-positive
      advanced/MBC in second-line or later patients. Part 2 of each module will enroll patients
      with locally assessed HER2-positive breast cancer who have not received prior treatment for
      advanced/metastatic disease.
    

Trial Arms

NameTypeDescriptionInterventions
Module 1- T-DXd and DurvalumabExperimentalT-DXd and Durvalumab
  • Trastuzumab deruxtecan
  • Durvalumab
Module 2- T-DXd and PertuzumabExperimentalT-DXd and Pertuzumab
  • Trastuzumab deruxtecan
  • Pertuzumab
Module 3- T-DXd and PaclitaxelExperimentalT-DXd and Paclitaxel
  • Trastuzumab deruxtecan
  • Paclitaxel
Module 4- T-DXd and Durvalumab and PaclitaxelExperimentalT-DXd and Durvalumab and Paclitaxel
  • Trastuzumab deruxtecan
  • Durvalumab
  • Paclitaxel
Module 0- T-DXdExperimentalT-DXd
  • Trastuzumab deruxtecan
Module 5 - T-DXd and TucatanibExperimentalT-DXd and tucatinib
  • Trastuzumab deruxtecan
  • Tucatinib
Module 6 - T-DXd and TucatinibExperimentalT-DXd and tucatinib in patients with active brain metastases (Part 2 Only)
  • Trastuzumab deruxtecan
  • Tucatinib
Module 7 - T-DXdExperimentalT-DXd monotherapy in patients with active brain metastases (Part 2 Only)
  • Trastuzumab deruxtecan

Eligibility Criteria

        Key Inclusion Criteria:

          -  Patients must be at least 18 years of age

          -  Pathologically documented breast cancer that:

               1. Is advanced/unresectable (patients that can be treated with curative intent are
                  not eligible) or metastatic

               2. HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment

               3. Is documented as hormone receptor-positive (estrogen or progesterone receptor) or
                  negative in the metastatic setting

          -  Patient must have adequate tumor sample for biomarker assessment

          -  ECOG Performance Status of 0 or 1

          -  Part 1

               1. Disease progression on or after the last systemic therapy prior to starting study
                  treatment

               2. At least 1 prior treatment line in metastatic setting required.

          -  Part 2 (Modules 0 - 5)

             a) No prior lines of therapy for advanced/MBC allowed

          -  Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed

        CNS Inclusion

          -  Modules 0 - 5 Patients must have no brain metastases or stable brain metastases.

          -  Module 6 and 7 Patients must have untreated brain metastases not needing local therapy
             or previously treated brain metastases that have progressed since prior local therapy

        Key Exclusion Criteria:

          -  Uncontrolled or significant cardiovascular disease

          -  Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or
             suspected ILD/pneumonitis that cannot be ruled out by imaging at screening

          -  Lung-specific intercurrent clinically significant illnesses

          -  Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals

          -  Spinal cord compression or a history of leptomeningeal carcinomatosis

          -  Prior treatment with immune checkpoint inhibitors

          -  Prior treatment with an ADC containing a topoisomerase I inhibitor

          -  Prior treatment with tucatinib

        CNS Exclusion

          -  Modules 0 - 5: Has untreated brain metastasis

          -  Module 6 and 7: Ongoing use of systemic corticosteroids for control of symptoms of
             brain metastases or brain lesion thought to require immediate local therapy
      
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 53 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 53 months
Safety Issue:
Description:ORR is defined as the proportion of patients who have a 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, assessed up to approximately 53 months
Safety Issue:
Description:PFS is defined as time from the date of randomization until the date of progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause.
Measure:Progression Free Survival 2 (PFS2)- Part 2
Time Frame:Assessed up to approximately 53 months
Safety Issue:
Description:PFS2 is defined as time from the date of randomisation until the date of progression on next line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy) or death; second progression will be defined according to local standard clinical practice.
Measure:Duration of Response (DoR)- Part 2
Time Frame:Until progression, assessed up to approximately 53 months
Safety Issue:
Description:DoR is defined as time from the date of first documented response 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 53 months
Safety Issue:
Description:OS is defined as time from the date of randomisation until the date of death due to any cause.
Measure:Serum Concentration of Trastuzumab Deruxtecan (T-DXd)
Time Frame:While on study drug up to study completion, approximately 53 months
Safety Issue:
Description:Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
Measure:Serum Concentration of Durvalumab
Time Frame:While on study drug up to study completion, approximately 53 months
Safety Issue:
Description:Determination of durvalumab concentration in serum at different time points after administration
Measure:Serum Concentration of Pertuzumab
Time Frame:While on study drug up to study completion, approximately 53 months
Safety Issue:
Description:Determination of pertuzumab concentration in serum at different time points after administration
Measure:Plasma Concentration of Paclitaxel
Time Frame:While on study drug up to study completion, approximately 53 months
Safety Issue:
Description:Determination of paclitaxel concentration in plasma at different time points after administration
Measure:Plasma Concentration of Tucatinib
Time Frame:While on study drug up to study completion, approximately 53 months
Safety Issue:
Description:Determination of tucatinib concentration in plasma at different time points after administration
Measure:Immunogenicity of trastuzumab deruxtecan
Time Frame:Up to follow-up period, approximately 53 months
Safety Issue:
Description:Percentage of patients who develop ADA for trastuzumab deruxtecan
Measure:Immunogenicity of Durvalumab
Time Frame:Up to follow-up period, approximately 53 months
Safety Issue:
Description:Percentage of patients who develop ADA for durvalumab
Measure:Immunogenicity of Pertuzumab
Time Frame:Up to follow-up period, approximately 53 months
Safety Issue:
Description:Percentage of patients who develop ADA for pertuzumab

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Breast Cancer
  • HER2-positive
  • Brain Metastases
  • Trastuzumab Deruxtecan
  • T-DXd
  • DS-8201a
  • DESTINY-Breast07
  • Anti-HER2 Antibody Drug Conjugate (ADC)

Last Updated

February 4, 2021