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:

Not yet 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

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. 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

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

        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
      
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 40 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 40 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 40 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 40 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 40 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 40 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 40 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 40 months
Safety Issue:
Description:Determination of durvalumab concentration in serum at different time points after administration
Measure:Immunogenicity of trastuzumab deruxtecan
Time Frame:Up to follow-up period, approximately 40 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 40 months
Safety Issue:
Description:Percentage of patients who develop ADA for durvalumab
Measure:Immunogenicity of Pertuzumab
Time Frame:Up to follow-up period, approximately 40 months
Safety Issue:
Description:Percentage of patients who develop ADA for pertuzumab

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

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

Last Updated

August 31, 2020