Trastuzumab Deruxtecan (T-DXd) With Pyrotinib in First-line HER2-positive Unresectable or Metastatic Breast Cancer Trial

NCT06245824 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: D9673L00011
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This is an exploratory, single-arm, multi-center study to assess the efficacy and safety of T-DXd combined with pyrotinib as the first-line treatment of HER2-positive metastatic breast cancer. This study is planned to recruit 3 to 12 patients in safety run-in (Part A) and 39 to 42 patients in dose expansion (Part B) in several investigational sites in China. The total number of patients enrolled in the study will be 45 to 51. Among them, 45 patients will start at the recommended dose. Patients who fulfill all the inclusion criteria and none of the exclusion criteria will receive T-DXd combined with pyrotinib until confirmed progressive disease. Patients will attend a safety follow up visit 40 days after last dose of T-DXd with pyrotinib. There are two main parts to this study; Part A, Combination dose finding and Parts B, Dose expansion. Tumor assessments will be performed at Screening as baseline with follow-up every 9 weeks(±7 days) from the date of first dosing date of T-DXd with pyrotinib for 54 weeks, and then every 12 weeks (±7 days) until confirmed objective disease progression. Primary Objective for Part A: To define the recommended dose of pyrotinib combined with T-DXd Recommended dose Secondary Objective for Part A: To investigate the safety and tolerability of T-DXd + pyrotinib as first-line treatment of HER2-positive metastatic breast cancer. Primary Objective for Part B : To determine the efficacy of T-DXd + pyrotinib as first-line treatment of HER2-positive metastatic breast cancer. Secondary Objective for Part B : To further determine the efficacy of T-DXd + pyrotinib as first-line treatment of HER2-positive metastatic breast cancer and To further evaluate the safety and tolerability profile of T-DXd + pyrotinib as first-line treatment of HER2-positive metastatic breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) based on investigator assessment

  PFS is defined as the time from first dose of T-DXd + Pyrotinib until progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator or death due to any cause prior to disease progression（PD）.

  Up to 49 months (data cut-off)

Secondary Outcomes (7)

• Progression free survival rate at 12 months (PFS12)

  Up to 12 months.

• Progression free survival rate at 24 months (PFS24)

  Up to 24 months

• Objective response rate (ORR)

  Up to 49 months (data cut-off)

• Duration of response (DoR)

  Up to 49 months (data cut-off)

• Overall survival rate at 12 months (OS12)

  Up to 12 months

Study Arms (1)

All the subjects enrolled will receive the experimental intervention

EXPERIMENTAL

Participants will receive 5.4 mg/kg of T-DXd as IV infusion q3w, along with pyrotinib 400mg or 320mg (depend on recommended dose) orally once a day within 30 minutes after breakfast for a 21-day cycle.

Drug: Trastuzumab deruxtecan (T-DXd) with pyrotinib

Interventions

Trastuzumab deruxtecan (T-DXd) with pyrotinib DRUG

T-DXd, 5.4mg/kg IV day 1 of a 21-day cycle. Pyrotinib, 400mg or 320mg, orally once a day, daily of a 21-day cycle.

Also known as: (T-DXd) with pyrotinib

All the subjects enrolled will receive the experimental intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Aged at least 18 years.
• Pathologically documented breast cancer that：
• is advanced or metastatic;
• is confirmed as HER2-positive Immunohistochemistry 3+（IHC3+） or in situ hybridization+(ISH+) in the pathological examination/rechecking of primary lesions or metastatic lesions performed by the Research site's Patholog Laboratory;
• hormone receptor (HR)-positive or HR-negative disease
• 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
• Asymptomatic or treated brain metastases not needing urgent neurosurgical intervention or dehydration treatment and glucocorticoid treatment is allowed：
• Untreated brain metastases (BM) at contrast brain screening MRI/CT
• Previously local therapy treated stable or progressing brain metastases (BM).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Having at least one measurable lesion according to RECIST 1.1.
• left ventricular ejection fraction ≥ 50% within 28 days at screening.
• Life expectancy ≥ 12 weeks at screening.
• Adequate organ and bone marrow function within 28 days before randomization/enrolment as described below. Organ and bone marrow function criteria must also be met when laboratory tests are repeated within 3 days before Cycle 1 Day 1. Note: Transfusion (red blood cell or platelet) or Granulocyte Colony-Stimulating Factor administration is not allowed within 2 weeks prior to the day on which marrow function is assessed:

You may not qualify if:

• Ineligible for any of the agents on the study. Participants with contraindications to pyrotinib per local prescribing information or to T-DXd per the T-DXd Investigator's Brochure cannot be enrolled to the study.
• Previous IP（pyrotinib or T-DXd）assignment in the present study, or prior treatment with any other HER2 TKI agent.
• Prior exposure to antibody drug conjugate that comprises of an exatecan derivative that is a topoisomerase I inhibitor.
• Any concurrent anticancer treatment. A 3-week washout period is required for female participants using hormone replacement therapy and for participants receiving endocrine therapy for HR positive tumours.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Refractory nausea, vomiting and diarrhea, chronic gastrointestinal disease, or previous significant bowel resection.
• Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 5 years before the first dose of study treatment and of low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy, adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumours curatively treated.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline. Note: Participants may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to \>Grade 2 for at least 3 months prior to first exposure to study intervention and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, including:
• Chemotherapy-induced neuropathy
• Fatigue
• Residual toxicities from prior immuno-oncology treatment: Grade 1 or Grade 2 endocrinopathies which may include:
• Hypothyroidism/hyperthyroidism
• Type 1 diabetes
• Hyperglycemia

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Binghe Xu

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Binghe Xu, Doctor

CONTACT

+86 13501028690; xubh@cicams.ac.cn

Ying Fan

CONTACT

+86 13693656671; fanyingfy@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2023
• First Posted: February 7, 2024
• Study Start: January 30, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)