Breast Cancer; HER2-positive; Metastatic
Conditions
Keywords
Breast Neoplasms; Breast Diseases; Trastuzumab; Antineoplastic Agents, Phytogenic; Anti-drug conjugate; Molecular Mechanisms of Pharmacological Action;
Brief summary
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.
Detailed description
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.
Interventions
DRUGTrastuzumab deruxtecan
Administered by intravenous infusion
DRUGPlacebo
Administered by intravenous infusion
DRUGTaxane
Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion
DRUGPertuzumab
Administered by intravenous infusion
DRUGTrastuzumab
Administered by intravenous infusion
Sponsors
AstraZeneca
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study is open-label with respect to the control arm. Pertuzumab/placebo in the experimental arms will be blinded to the investigator and patients. The study will be "Sponsor-blind". To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.
Intervention model description
Study will consist of three arms: Arm A - trastuzumab deruxtecan with pertuzumab-matching placebo Arm B - trastuzumab deruxtecan with pertuzumab Arm C - standard of care (taxane \[docetaxel or paclitaxel\], trastuzumab and pertuzumab)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment | Until progression or death, assessed up to approximately 60 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) by Investigator assessment | Until progression or death, assessed up to approximately 60 months | 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. |
| Overall Survival (OS) | Until death, assessed up to approximately 104 months | OS is defined as the time from randomisation until the date of death due to any cause. |
| Objective Response Rate (ORR) by BICR and Investigator assessment | Until progression or death (in the absence of progression), assessed up to approximately 60 months | 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. |
| Duration of Response (DoR) by BICR and Investigator Assessment | Until progression or death (in the absence of progression), assessed up to approximately 60 months | 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 to second progression or death (PFS2) by Investigator assessment | Assessed up to approximately 104 months | 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. |
| 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'. | Assessed up to approximately 60 months | 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. |
| To assess patient-reported treatment tolerability | Assessed up to approximately 60 months | 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. |
| Serum concentration of trastuzumab deruxtecan and pertuzumab | Up to Cycle 6, approximately Week 18; each cycle is 21 days | Determination of trastuzumab deruxtecan and pertuzumab concentrations in serum. |
| Immunogenicity of trastuzumab deruxtecan. | Up to follow-up period, approximately 60 months | Number and percentage of participants who develop anti-drug antibody (ADA) for trastuzumab deruxtecan. |
| Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab | Assessed up to approximately 60 months | Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm |
Countries
Argentina, Belgium, Brazil, Canada, China, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Mexico, Peru, Philippines, Romania, Russia, Saudi Arabia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed