KN026 plus HB1801 with chemotherapy as adjuvant treatment after surgery for resectable HER2-positive breast cancer

A Randomized, Controlled, Open-label, Multicenter, Phase III Clinical Study to Evaluate the Efficacy and Safety of KN026 Combined With HB1801 and Chemotherapy Versus Trastuzumab Combined With Pertuzumab and Chemotherapy as Adjuvant Therapy in Resectable HER2-positive Breast Cancer

This study will test whether giving KN026 and HB1801 with chemotherapy after surgery helps people with resectable HER2-positive breast cancer more than the usual trastuzumab plus pertuzumab with chemotherapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1800 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai JMT-Bio Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, trastuzumab, pertuzumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07441460 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label, multicenter Phase III trial comparing KN026 combined with HB1801 plus chemotherapy to the standard trastuzumab plus pertuzumab with chemotherapy as adjuvant treatment for patients with resectable HER2-positive breast cancer. Eligible participants are adults who have had definitive breast surgery and have pathologically positive regional lymph nodes, good performance status, and adequate organ function. Participants will be assigned to one of the two treatment arms and followed for safety and efficacy outcomes, including recurrence and survival endpoints. The protocol requires cardiac monitoring and standard laboratory testing given the known cardiac and hematologic risks of HER2-targeted agents and chemotherapy.

Who should consider this trial

Good fit: Adults (≥18) with resectable HER2-positive invasive breast cancer who have completed definitive surgery with node-positive disease, ECOG 0–1, adequate organ and marrow function, and LVEF ≥55% are ideal candidates.

Not a fit: Patients with HER2-negative disease, unresectable or metastatic cancer, poor performance status (ECOG >1), significant organ dysfunction, or inadequate cardiac function are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this regimen could lower the risk of cancer recurrence and offer an alternative HER2-directed adjuvant option with comparable or improved outcomes.

How similar studies have performed: Dual HER2-targeting with trastuzumab plus pertuzumab has shown benefit in perioperative and adjuvant settings, while bispecific HER2 agents like KN026 are newer and have shown promising early-phase results but are less established in Phase III adjuvant use.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily participate and sign the informed consent form.
2. Age ≥ 18 years.
3. ECOG performance status score of 0 or 1.
4. Histologically or cytologically confirmed invasive breast cancer.
5. Must have undergone prior radical mastectomy or breast-conserving surgery for breast cancer.
6. Pathologically confirmed positive regional lymph nodes.
7. Tumor tissue confirmed as HER2-positive by the local laboratory.
8. Adequate organ and bone marrow function:

   1. Absolute neutrophil count ≥ 1.5 × 10⁹/L
   2. Platelet count ≥ 100 × 10⁹/L
   3. Hemoglobin ≥ 90 g/L
   4. Liver function: Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for participants with Gilbert's syndrome); ALT and AST ≤ 2.5 × ULN; Alkaline phosphatase ≤ 2.5 × ULN
   5. Coagulation function: INR ≤ 1.5 × ULN and aPTT ≤ 1.5 × ULN
   6. Renal function: Creatinine clearance ≥ 50 mL/min
   7. LVEF ≥ 55%
9. Female participants of childbearing potential must have a negative blood pregnancy test result within 7 days prior to randomization, and agree to use reliable and effective contraception during the study treatment period and for 7 months after the last dose of study treatment. Male participants with female partners of childbearing potential must agree to use reliable and effective contraception during the study treatment period and for 7 months after the last dose of study treatment.

Exclusion Criteria:

1. History of any prior ipsilateral and/or contralateral invasive breast cancer.
2. History of other malignancy within 5 years prior to randomization, except for the breast cancer under study and locally curable malignancies treated with curative intent.
3. Prior systemic chemotherapy, endocrine therapy, anti-HER2 targeted therapy, or local radiotherapy for breast cancer.
4. Use of strong CYP3A4 inhibitors within 14 days prior to randomization or planned use during the combination chemotherapy period.
5. Known contraindication to any study drug or history of hypersensitivity to any component or known excipient of the study drugs.
6. Significant cardiovascular disease history, including: prior coronary artery bypass graft or coronary stenting; myocardial infarction or cerebrovascular accident within 6 months prior to randomization; history of congestive heart failure/systolic dysfunction (LVEF \< 50%) or unstable angina; history of clinically significant prolonged QT interval or QTcF (Fridericia) \> 450 ms at screening; uncontrolled severe hypertension (systolic BP \> 180 mmHg and/or diastolic BP \> 100 mmHg); high-risk arrhythmias \[e.g., atrial tachycardia with resting heart rate ≥ 100 bpm, significant ventricular arrhythmia (ventricular tachycardia), or high-grade atrioventricular block (Mobitz type II second-degree or third-degree AV block)\].
7. Severe chronic or active infection requiring intravenous anti-infective therapy within 14 days prior to randomization.
8. Participation in another interventional clinical trial within 4 weeks prior to randomization.
9. Pregnant or lactating women.
10. Any other condition that may interfere with the participant's ability to comply with study procedures, may not be in the participant's best interest to participate, or may affect study results (e.g., history of neurological or psychiatric disorders, alcohol or drug abuse, or any other clinically significant disease or condition).

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Clinical Trials Information Group officer

Conditions Resectable HER2-positive Breast Cancer