Trastuzumab Rezetecan Neoadjuvant Therapy in THP-Insensitive HER2-Positive Early Breast Cancer

Sponsor
The First Affiliated Hospital of Soochow University
Study ID
NCT07647263
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • THP Regimen (Taxane + Trastuzumab + Pertuzumab) — DRUG
    Neoadjuvant combination therapy consisting of a taxane, trastuzumab, and pertuzumab. Administered as initial treatment to all patients, and continued for responders.
  • Trastuzumab Rezetecan (SHR-A1811) — DRUG
    HER2-targeted antibody-drug conjugate (ADC). Administered to patients with inadequate response to initial THP therapy.

Study Details

This study is a response-adapted, multicenter, interventional trial enrolling patients with HER2-positive early or locally advanced breast cancer. All enrolled patients will first receive 2 cycles of standard neoadjuvant THP regimen, consisting of a taxane, trastuzumab, and pertuzumab. After the initial 2-cycle treatment, tumor response will be evaluated by radiologic imaging and patient-derived organoid (PDO) drug sensitivity testing. Patients with an inadequate response to THP are defined as those with \<50% tumor size reduction on imaging, or failure to reach the PDO sensitivity threshold (\<80% tumor cell killing for HER2+/HR- tumors; \<60% for HER2+/HR+ tumors). These non-responders will switch to receive 4 cycles of trastuzumab rezetecan (SHR-A1811), a novel HER2-targeted antibody-drug conjugate (ADC). Patients with a favorable response (≥50% tumor reduction or meeting the PDO threshold) will continue with an additional 4 cycles of THP. The primary objective is to evaluate the pathologic complete response (pCR) rate in THP non-responders after switching to trastuzumab rezetecan. Secondary objectives include objective response rate (ORR), event-free survival (EFS), overall survival (OS), 3-year invasive disease-free survival (iDFS), and safety profiles of both treatment strategies. Outcomes in patients who continue THP will be described for exploratory purposes. A total of 124 patients will be enrolled. This response-adapted, individualized strategy aims to provide an effective option for HER2-positive breast cancer patients with an inadequate early response to conventional THP neoadjuvant therapy.

Key Dates

First listed
Jun 15, 2026
Start date
Mar 24, 2026
Status verified
May 2026
Primary completion
Jun 30, 2029
Completion
Dec 31, 2031

Study Design

Enrollment
124 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Active Comparator: THP Continuation Arm
    All patients first receive 2 cycles of neoadjuvant THP (taxane + trastuzumab + pertuzumab). Patients with favorable response (≥50% tumor reduction or meeting PDO sensitivity threshold) continue with 4 additional cycles of THP.
  • Experimental: SHR-A1811 Switch Arm
    All patients first receive 2 cycles of neoadjuvant THP (taxane + trastuzumab + pertuzumab). Patients with inadequate response (\<50% tumor reduction or failing PDO sensitivity threshold) switch to 4 cycles of trastuzumab rezetecan (SHR-A1811).

Primary Outcome Measure

Pathologic Complete Response (tpCR) Rate [ Time Frame: Perioperative ]

Central Contacts

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