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

Sponsor: AstraZeneca

Sponsor score: 40

ClinicalTrials ID:NCT04538742

DESTINY-Breast07 is a modular Phase 1b/2 trial assessing the safety, tolerability, and anti-tumor activity of T-DXd with other agents in HER2-positive metastatic breast cancer. Eligible patients are 18+, with advanced/metastatic HER2-positive cancer. Interventions include T-DXd, durvalumab, paclitaxel, pertuzumab, and tucatinib. The study includes dose-finding and expansion phases.

Patient Parameters

Program Overview

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

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.

Eligibility Criteria

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. The local HER2 result must be from a tumour sample obtained in the metastatic setting.
    3. Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting

  • Patient must have adequate tumor sample from the metastatic setting 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 at a total daily dose of > 2 mg dexamethasone or any brain lesion thought to require immediate local therapy

Locations

FACILITYZIPCITYSTATE
Research Site33901Fort MyersFlorida
Research Site33705St. PetersburgFlorida
Research Site11725CommackNew York
Research Site10604HarrisonNew York
Research Site10016New YorkNew York
Research Site10065New YorkNew York
Research Site43219ColumbusOhio
Research Site37203NashvilleTennessee
Research Site76104Fort WorthTexas
Research Site22031FairfaxVirginia

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