Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive Metastatic Breast Cancer (DESTINY-Breast09)

Phase 3Active Not RecruitingNCT04784715

AstraZeneca1,157 enrolled

Overview

The study will evaluate the efficacy and safety of trastuzumab deruxtecan (also known as T-DXd, DS-8201a), either alone or in combination with pertuzumab, in treating patients with Human epidermal growth factor receptor 2 (HER2)-positive breast cancer as a first line of treatment in the metastatic setting.

Eligible participants will be those diagnosed with HER2-positive (IHC 3+ or ISH+), metastatic breast cancer, who have received no prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer. The study aims to evaluate the efficacy, and safety of trastuzumab deruxtecan, alone or with pertuzumab, compared with the standard of care treatment (taxane \[docetaxel or paclitaxel\], trastuzumab and pertuzumab). This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,157

Conditions

Breast Cancer; HER2-positive; Metastatic

Interventions

Trastuzumab deruxtecanDRUG

Administered by intravenous infusion

PlaceboDRUG

Administered by intravenous infusion

TaxaneDRUG

Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Patients must be ≥18 years of age * Pathologically documented breast cancer that: 1. is advanced or metastatic 2. is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+) 3. is documented by local testing as hormone receptor (HR)-positive or HR-negative disease in the metastatic setting * No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer or only 1 previous line of endocrine therapy in the metastatic setting. Participants who have received chemotherapy or HER2-targeted therapy in the neo-adjuvant or adjuvant setting are eligible if \> 6 months from treatment to metastatic diagnosis. * Has protocol-defined adequate organ and bone marrow function * ECOG performance status 0 or 1 Key Exclusion Criteria: * Ineligible for any of the agents on the study. * Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with subject's participation or study results * Patients with spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic may be included in the study. * Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening * Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment

Locations (283)

Outcomes

Primary Outcomes

Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment

Defined as time from date of randomisation until the date of objective radiological disease progression according to Blinded Independent Central Review (BICR) using RECIST 1.1 or death by any cause.

Time frame: Until progression or death, assessed up to approximately 60 months

Secondary Outcomes

Progression Free Survival (PFS) by Investigator assessment

Defined as time from date of randomisation until the date of objective radiological disease progression according to Investigator using RECIST 1.1 or death by any cause.

Time frame: Until progression or death, assessed up to approximately 60 months

Overall Survival (OS)

OS is defined as the time from randomisation until the date of death due to any cause.

Time frame: Until death, assessed up to approximately 104 months

Objective Response Rate (ORR) by BICR and Investigator assessment

ORR is defined as The proportion of participants who have a complete response (CR) or partial response (PR) based on BICR and investigator assessment using RECIST 1.1.

Time frame: Until progression or death (in the absence of progression), assessed up to approximately 60 months

Duration of Response (DoR) by BICR and Investigator Assessment

DoR is defined as the time from date of first detection of objective response until the date of objective radiological disease progression according to BICR and investigator assessment using RECIST 1.1 or death in the absence of progression.

Time frame: Until progression or death (in the absence of progression), assessed up to approximately 60 months

Time to second progression or death (PFS2) by Investigator assessment

Data from ClinicalTrials.gov

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Administered by intravenous infusion

TrastuzumabDRUG

Administered by intravenous infusion

Research Site

Tucson, Arizona, United States

Research Site

Springdale, Arkansas, United States

Research Site

Glendale, California, United States

Research Site

Glendale, California, United States

Research Site

Longmont, Colorado, United States

Research Site

Miami, Florida, United States

Research Site

Palm Bay, Florida, United States

Research Site

Plantation, Florida, United States

Research Site

Atlanta, Georgia, United States

Research Site

Louisville, Kentucky, United States

...and 273 more locations

PFS2 is defined as the time from randomisation until the date of tumor progression on next-line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy after the first progression) or death from any cause; second progression will be defined according to local standard clinical practice.

Time frame: Assessed up to approximately 104 months

To assess the effect of T-DXd ± pertuzumab relative to THP in terms of patient-reported pain in participants with HER2 positive, first-line mBC'.

Pain progression: Time to sustained deterioration of European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Pain Scale. Scores range from 0-100 based on 2 items with responses ranging from 1-4. A lower score would mean better outcome.

Time frame: Assessed up to approximately 60 months

To assess patient-reported treatment tolerability

Proportion of participants experiencing treatment related symptoms as measured by selected items from the European Organisation for Research and Treatment of Cancer, general cancer module (EORTC QLQ-C30), score of 1-4. A lower score would mean better outcome.

Time frame: Assessed up to approximately 60 months

To assess patient-reported treatment tolerability

Proportion of patients reporting different levels of overall tolerability as measured by the Patient Global Impression of Treatment Tolerability (PGI-TT), score of 0-4. A lower score would mean a better outcome.

Time frame: Assessed up to approximately 60 months

To assess patient-reported treatment tolerability

Proportion of participants experiencing treatment related symptoms as measured by selected items from the European Organisation for Research and Treatment of Cancer, breast cancer module (EORTC QLQ-BR45), score of 1-4. A lower score would mean better outcome.

Time frame: Assessed up to approximately 60 months

To assess patient-reported treatment tolerability

Proportion of participants experiencing treatment related symptoms as measured by selected items from the Patient-Reported Outcomes- Common Terminology Criteria for Adverse Events (PRO-CTCAE). PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present). A lower score would mean a better outcome.

Time frame: Assessed up to approximately 60 months

To assess patient-reported treatment tolerability

The proportion of participants with maintained or improved physical function while on treatment, based on the EORTC QLQ-C30 Physical Functioning scale. Scores range from 0-100, based on 5 items with responses ranging from 1-4. A higher score would mean a better outcome.

Time frame: Assessed up to approximately 60 months

Serum concentration of trastuzumab deruxtecan and pertuzumab

Determination of trastuzumab deruxtecan and pertuzumab concentrations in serum.

Time frame: Up to Cycle 6, approximately Week 18; each cycle is 21 days

Immunogenicity of trastuzumab deruxtecan.

Number and percentage of participants who develop anti-drug antibody (ADA) for trastuzumab deruxtecan.

Time frame: Up to follow-up period, approximately 60 months

Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab

Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm

Time frame: Assessed up to approximately 60 months