SHR-A1811 vs Pyrotinib/Capecitabine in Trastuzumab-Resistant HER2+ Advanced Breast Cancer: A Randomized Study

NCT07417241 | Not Yet Recruiting Phase 2

• 1 other identifier: OBU-BC-II-300
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, multicenter, open-label, randomized, controlled Study. The purpose of this study is to evaluate the efficacy and safety of SHR-A1811 versus pyrotinib plus capecitabine in the treatment of trastuzumab primary-resistant HER2-positive advanced breast cancer.

Conditions

Breast Cancer; HER2-positive Breast Cancer

Keywords

HER2-positive breast cancer; SHR-A1811

Outcome Measures

Primary Outcomes (1)

• PFS during treatment phase 1

  progression free survival during treatment phase 1 : time from randomization to the first observation of tumor progression or death from any cause during treatment phase 1.

  Start of treatment until 2-year follow-up

Secondary Outcomes (9)

• Total PFS across treatment phase 1 and treatment phase 2

  Start of treatment until 3-year follow-up

• PFS during treatment phase 2

  Start of treatment until 3-year follow-up

• ORR during treatment phase 1

  Start of treatment until 2-year follow-up

• DCR during treatment phase 1

  Start of treatment until 2-year follow-up

• OS

  Start of treatment until 3-year follow-up

Study Arms (2)

Arm 1

EXPERIMENTAL

Treatment Phase 1: SHR-A1811 monotherapy until progression or intolerable adverse events. Treatment Phase 2: Switch to pyrotinib plus capecitabine upon progression from Phase 1, continued until subsequent progression or intolerable adverse events.

Drug: SHR-A1811; Drug: Pyrotinib; Drug: Capecitabine

Arm 2

ACTIVE COMPARATOR

Treatment Phase 1: Pyrotinib plus capecitabineuntil progression or intolerable adverse events. Treatment Phase 2: Switch to T-DXd upon progression from Phase 1, continued until subsequent progression or intolerable adverse events.

Drug: Pyrotinib; Drug: Capecitabine; Drug: T-DXd

Interventions

SHR-A1811 DRUG

4.8 mg/kg administered as an intravenous infusion on Day 1 of each cycle. 3 weeks a cycle. Continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.

Arm 1

Pyrotinib DRUG

400 mg, administered orally once daily, continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.

Arm 1; Arm 2

Capecitabine DRUG

1000mg/m2, administered orally twice daily on Days 1-14, with no administration on Days 15-21, 3 weeks a cycle. Continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.

Arm 1; Arm 2

T-DXd DRUG

5.4 mg/kg administered as an intravenous infusion on Day 1 of each cycle. 3 weeks a cycle. Continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.

Arm 2

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Histologically or cytologically confirmed HER2-positive advanced breast cancer (IHC 3+, or IHC 2+ with ISH amplification).
• ECOG performance status 0-2.
• Estimated life expectancy \>12 weeks.
• At least one measurable lesion per RECIST v1.1 criteria;
• Patients with trastuzumab primary resistance is defined as follows:
• Progression during or within 12 months after treatment in neoadjuvant or adjuvant setting (at least 9 weeks of trastuzumab treatment);
• For patients with de novo stage IV disease, progression during or within 3 months after treatment for locally advanced or metastatic disease in the first-line setting (at least 6 weeks of trastuzumab treatment).
• Adequate organ function as defined by the following laboratory criteria:
• Hematologic: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count (PLT) ≥100 × 10⁹/L, hemoglobin (HGB) ≥90 g/L.
• Hepatic: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN) (≤5 × ULN in patients with liver metastases); total serum bilirubin (TBIL) ≤1.5 × ULN; serum albumin ≥30 g/L.
• Renal: serum creatinine (Cr) ≤1.5 × ULN or calculated creatinine clearance ≥50 mL/min using the Cockcroft-Gault formula.
• Coagulation: prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5 × ULN.
• Cardiac: left ventricular ejection fraction (LVEF) ≥50%.
• Women of childbearing potential must have a negative pregnancy test at screening, and subjects of reproductive potential must agree to use effective contraception from study start until 6 months after the last dose of study treatment..

You may not qualify if:

• Prior or current exposure to antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, including but not limited to fam-trastuzumab deruxtecan (DS-8201a).
• Active brain metastases or leptomeningeal metastases (patients with asymptomatic/inactive brain metastases are allowed to be enrolled);
• Other malignancy diagnosed within 5 years prior to enrollment, excluding cured non-melanoma skin cancer, cervical carcinoma in situ, ductal carcinoma in situ, or stage I grade 1 endometrial cancer;
• Radiotherapy, any anti-HER2 targeted therapy, or chemotherapy within 4 weeks prior to enrollment; endocrine therapy within 2 weeks prior to enrollment;
• Positive for human immunodeficiency virus (HIV);
• Known hypersensitivity to any study drug or its excipients, or to humanized monoclonal antibody products (e.g., trastuzumab, pertuzumab, etc.);
• Clinically significant cardiovascular disease, such as severe/unstable angina, symptomatic congestive heart failure (NYHA Class ≥II), clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, myocardial infarction within 6 months prior to first dose, or cerebrovascular accident (including transient ischemic attack).
• Participants known or suspected to interstitial lung disease.
• Concurrent participation in any other interventional drug clinical trial.
• Refusal to comply with protocol-mandated follow-up. Presence of any additional severe physical or psychiatric disorder, or any laboratory abnormality that, in the investigator's judgment, could increase the subject's risk, confound study results, or render the patient unsuitable for enrollment.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Hanfang Jiang

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hanfang Jiang

CONTACT

+86-010-88196380; hfjiangcn@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: February 18, 2026
• Study Start: March 31, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 18, 2026

Record last verified: 2026-02