HLX22 plus trastuzumab deruxtecan for HER2-low, hormone receptor–positive advanced breast cancer

A Phase II Study of HLX22 (Recombinant Humanized Anti-HER2 Monoclonal Antibody Injection) in Combination With Trastuzumab Deruxtecan (T-DXd) in HER2-low, Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Patients With Intolerable Adverse Reaction or Disease Progression on Standard of Care

This will test whether adding HLX22 to trastuzumab deruxtecan helps people with HER2-low, hormone receptor–positive advanced breast cancer who have progressed on or could not tolerate standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Henlius Biotech (Industry-sponsored)
• Drugs / interventions: Trastuzumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06832202 on ClinicalTrials.gov

What this trial studies

This Phase II, interventional trial gives eligible patients HLX22 (15 mg/kg) combined with trastuzumab deruxtecan (5.4 mg/kg) every three weeks. Participants have HER2-low, hormone receptor–positive locally advanced or metastatic breast cancer with measurable disease and prior progression or intolerance to standard care. Treatment continues until loss of clinical benefit, unacceptable toxicity, death, or withdrawal of consent. Key eligibility includes ECOG 0–1, expected survival ≥6 months, adequate organ function, and no prior HER2-targeted therapy or prior interstitial lung disease.

Who should consider this trial

Good fit: Ideal candidates are adults with centrally confirmed HER2-low, hormone receptor–positive locally advanced or metastatic breast cancer with measurable disease, ECOG 0–1, adequate organ function, and prior progression or intolerance on standard therapies.

Not a fit: Patients who previously received any HER2-targeted therapy, have prior interstitial lung disease/pneumonitis, uncontrolled cardiovascular disease, other recent malignancies, or poor performance status are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combination could prolong tumor control or delay progression for patients with HER2-low, HR-positive advanced breast cancer who have limited options.

How similar studies have performed: Trastuzumab deruxtecan has demonstrated clear benefit in HER2-low metastatic breast cancer (e.g., DESTINY-Breast04), but combining it with HLX22 is a newer approach and remains investigational.

Eligibility criteria

Inclusion Criteria:

1. Male/female who are at least 18 years of age on the day of signing the informed consent.
2. With histologically confirmed diagnosis of HER2-low, Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer.
3. HER2-low defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) as assessed by a central laboratory on metastatic tumor and was never previously HER2-positive，and was documented HR+ disease in the metastatic setting
4. Had measurable disease according to the RECIST v1.1, the target lesion must not be a bone metastatic lesion only.
5. ECOG PS: 0-1.
6. Expected survival ≥ 6 months.
7. Had adequate organ function

Exclusion Criteria:

1. Patients with other malignant tumors within 3 years before the randomization
2. Previous treatment with any HER2-target therapy
3. Uncontrolled or significant cardiovascular disease or infection
4. Lung-specific intercurrent clinically significant illnesses
5. Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis
6. Patients with spinal cord compression or clinically active central nervous system metastases

Where this trial is running

Shanghai, Shanghai Municipality

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

Study contacts

• Study coordinator: Yun Li

Conditions HER2-low Hormone Receptor Positive Breast Cancer