Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer

Phase 3RecruitingNCT05950945

Daiichi Sankyo250 enrolled

Overview

This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor \[HR\]-negative and HR-positive) unresectable and/or metastatic breast cancer.

The primary endpoint of interest in this study is time to next treatment (TTNT), a measure that will determine how long T-DXd allows patients to derive clinical benefit from the study drug.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

250

Conditions

Breast Cancer

Interventions

Trastuzumab DeruxtecanDRUG

Intravenous administration, 5.4 mg/kg on Day 1 of each 21-day cycle until radiographic disease progression as assessed by the investigator, unacceptable toxicity, other discontinuation criteria are met, or 2 years after first dose of study drug

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Sign and date the main informed consent form * Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion. * Pathologically documented Breast Cancer (BC) tumor * Is unresectable and/or metastatic. * Is hormone receptor-negative or hormone receptor-positive. * Must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative. * Has confirmed HER2 IHC 1+ or IHC 2+/ISH- (HER2-low) status or HER2 IHC 0 status as determined according to ASCO CAP 2018 guidelines1 based on sample collected during Tissue Screening as described above. * Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per ASCO CAP guidelines). * Was never previously treated with anti-HER2 therapy in the metastatic setting. * Has had at least one and up to two prior lines of therapy in the metastatic setting. * In participants with hormone receptor-positive HER2-low metastatic BC (Cohort 3): * Has recurrent disease \<2 years from the initiation of adjuvant ET OR * Has disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor OR * Has disease progression within the first 12 months of CDK4/6 in the first line metastatic setting * Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging. * Participants with brain metastases are allowed in the study. The brain lesion(s) should be small (\<2 cm), untreated, asymptomatic, not requiring urgent medical intervention, and are asymptomatic and clinically stable. * Has an Eastern Cooperative Oncology Group performance status of 0 or 1. * Has a minimum life expectancy of 12 weeks at Screening. * Has a left ventricular ejection fraction ≥50% within 28 days before enrollment. * Has adequate organ and bone marrow function within 28 days before enrollment. * Has adequate treatment washout period before enrollment. * Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception. Exclusion Criteria: * Prior treatment with an antibody drug conjugate (ADC). * Uncontrolled or significant cardiovascular disease. * Has a corrected QT interval prolongation. * Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. * Has spinal cord compression or clinically active central nervous system metastases. * Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral BC. * Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product. * Has a history of severe hypersensitivity reactions to other monoclonal antibodies. * Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals. * Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. * Has history of receiving a live, attenuated vaccine (messenger RNA and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study drug. * Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline. * Is pregnant or breastfeeding or planning to become pregnant. * Lung-specific intercurrent clinically significant illnesses. * Any autoimmune, connective tissue, or inflammatory disorders. * Prior complete pneumonectomy.

Locations (86)

Outcomes

Primary Outcomes

Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT)

TTNT is defined as the time interval from the date of first dose of T-DXd to the initiation of the next anticancer treatment or death due to any cause.

Time frame: Until subsequent therapy or death, assessed up to 24 months

Secondary Outcomes

Real-World Progression Free Survival (PFS)

Real-world PFS is defined as time from date of first dose of T-DXd to time of disease progression per investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause.

Time frame: Until progression or death, assessed up to 24 months

Time From Start of T-DXd to Discontinuation of T-DXd or Death (TTD)

TTD is defined as the time interval from the date of first dose of T-DXd to the date of discontinuation of T-DXd or death due to any cause.

Time frame: Until treatment discontinuation or death, up to 24 months

Objective Response Rate (ORR)

ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to the investigator and per RECIST version 1.1 criteria.

Time frame: Until progression, assessed up to 24 months

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

TEAEs are graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. A TEAE is defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after initiating the study drug until 47 days after the last dose of the study drug.

Time frame: Up to follow up period, up to 24 months

Central Contacts

(US Sites) Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

908-992-6400 CTRinfo@dsi.com

(Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

+81-3-6225-1111 (M-F 9-5 JST)dsclinicaltrial@daiichisankyo.co.jp

Data from ClinicalTrials.gov

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