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

JRCT ID: jRCT2031210130

Registered date:04/06/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Breast Cancer; HER2-positive; Metastatic
• Date of first enrollment: 23/08/2021
• Target sample size: 1134
• Countries of recruitment: Argentina,Japan,Canada,Japan,China,Japan,Denmark,Japan,Hungary,Japan,India,Japan,Italy,Japan,Korea,Japan,Peru,Japan,Philippines,Japan,Russian Federation,Japan,Saudi Arabia,Japan,Saudi Arabia,Japan,Spain,Japan,Sweden,Japan,Taiwan,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Experimental: Arm A
Trastuzumab deruxtecan (T-DXd) with pertuzumab-matching placebo
Drug: Trastuzumab deruxtecan
Administered by intravenous infusion
Other Name: DS-8201a; T-DXd

Drug: Placebo
Administered by intravenous infusion

Experimental: Arm B
Trastuzumab deruxtecan (T-DXd) with pertuzumab
Drug: Trastuzumab deruxtecan
Administered by intravenous infusion
Other Name: DS-8201a; T-DXd

Drug: Pertuzumab
Administered by intravenous infusion

Active Comparator: Arm C
Standard of care
Drug: Taxane
Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion

Drug: Pertuzumab
Administered by intravenous infusion

Drug: Trastuzumab
Administered by intravenous infusion

Outcome(s)

• Primary Outcome: Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment

Secondary Outcome

1.Progression Free Survival (PFS) by Investigator assessment
2.Overall Survival (OS)
3.Objective Response Rate (ORR) by BICR and Investigator assessment
4.Duration of Response (DoR) by BICR and Investigator Assessment
5.Time to second progression or death (PFS2) by Investigator assessment
6.Health related quality of life (HRQoL) using the EORTC QLQ-C30
7.Time to deterioration in EORTC-QLQ-C30 scores
8.Health related quality of life (HRQoL) using the EORTC QLQ-BR45
9.Serum concentration of trastuzumab deruxtecan and pertuzumab
10.Immunogenicity of trastuzumab deruxtecan, alone or with pertuzumab
11.Safety and tolerability of trastuzumab deruxtecan, alone or with pertuzumab

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 130age old
• Gender: Both

Include criteria

- Patients must be >=18 years of age(>=20 years of age - applicable for Japan only)
- 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

Exclude 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

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT04784715