A Phase II Study of HLX22 in Combination With Trastuzumab and Chemotherapy in HER2-Positive Locally Advanced or Metastatic Breast Cancer Patients

A Multicenter, Randomized, Double-Blind, Controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of HLX22 in Combination With Trastuzumab and Chemotherapy Versus Placebo in Combination With Trastuzumab and Chemotherapy in Locally Advanced Unresectable and/or Metastatic HER2-Positive Breast Cancer Previously Treated With HER2 ADC

This is a phase II study of HLX22 in combination with trastuzumab and chemotherapy versus placebo in combination with trastuzumab and chemotherapy in locally advanced and/or metastatic HER2-Positive breast cancer previously treated with HER2 ADC. Eligible participants will be treated with the study drug until the loss of clinical benefit, intolerable toxicity, initiation of new anti-tumor therapy, voluntary withdrawal from the study by the patient, loss to follow-up, death, or when the investigator determines that the patient should be withdrawn from the study (whichever occurs first).

Study Overview

• Status: Not yet recruiting
• Conditions: HER2 + Breast Cancer
• Intervention / Treatment: Drug: HLX22; Drug: Trastuzumab; Drug: Capecitabine; Drug: Paclitaxel; Drug: Docetaxel; Drug: Eribulin; Drug: Vinorelbine

Detailed Description

Experimental group: HLX22 + trastuzumab + investigator's choice of chemotherapy, once every 3 weeks (Q3W).

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mingxia Xu; Phone Number: +86 18905266695; Email: Mingxia_Xu@henlius.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥ 18 years (or the legal age of adulthood per country-specific regulation) at the time of signing the ICF, male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or - Life expectancy of ≥ 6 months.
• Histologically confirmed breast cancer with radiologically or otherwise documented locally advanced unresectable and/or metastatic disease.
• HER2 positive confirmed by central laboratory.
• Hormone receptor (HR) status confirmed by local laboratory.
• Patients who have progressed after treatment containing within HER2 ADC
• Presence of at least one measurable lesion according to the RECIST v1.1.
• Adequate organ function

Exclusion Criteria:

• History of any other malignancy within 2 years prior to signing the ICF.
• Prior use of doxorubicin with a cumulative in vivo dose of > 360 mg/m2.
• Adverse events from prior anti-tumor treatment that have not resolved to Grade ≤ 1 or baseline level according to CTCAE v6.0.
• Uncontrolled or severe cardiovascular disease.
• History of cerebrovascular accident within 6 months prior to randomization.
• Current (non-infectious) interstitial lung disease (ILD)/pneumonia that requires steroid treatment.
• Active infection.
• Active tuberculosis.
• Presence of spinal cord compression or clinically symptomatic central nervous system metastases.
• Receipt of systemic anti-tumor treatment and immunotherapy, within 4 weeks prior to randomization
• Pregnant or lactating women or women who plan to become pregnant during the study period.
• History of immunodeficiency or history of organ transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; HLX22 + trastuzumab + investigator's choice of chemotherapy (capecitabine or paclitaxel or docetaxel or eribulin or vinorelbine)	Drug: HLX22; 15 mg/kg, intravenous infusion (IV) on Day 1 (D1) of Q3W; Drug: Trastuzumab; Loading dose 8 mg/kg, maintenance dose 6 mg/kg, IV, Q3W, D1.; Drug: Capecitabine; 1000 mg/m2, oral (po), twice daily (BID), D1-14, Q3W; Drug: Paclitaxel; 175 mg/m2, D1; or 80-90 mg/m2, D1 D8 D15, Q3W, IV; Drug: Docetaxel; 75-100 mg/m2, D1, Q3W, IV; Drug: Eribulin; 1.4 mg/m2, D1 and D8, Q3W, IV; Drug: Vinorelbine; 25-30 mg/m2, D1 and D8, Q3W, IV
Placebo Comparator: Control group; placebo + trastuzumab + investigator's choice of chemotherapy (capecitabine or paclitaxel or docetaxel or eribulin or vinorelbine)	Drug: Trastuzumab; Loading dose 8 mg/kg, maintenance dose 6 mg/kg, IV, Q3W, D1.; Drug: Capecitabine; 1000 mg/m2, oral (po), twice daily (BID), D1-14, Q3W; Drug: Paclitaxel; 175 mg/m2, D1; or 80-90 mg/m2, D1 D8 D15, Q3W, IV; Drug: Docetaxel; 75-100 mg/m2, D1, Q3W, IV; Drug: Eribulin; 1.4 mg/m2, D1 and D8, Q3W, IV; Drug: Vinorelbine; 25-30 mg/m2, D1 and D8, Q3W, IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) assessed by the blinded independent central review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	ORR is defined as the percentage of participants who have a Complete Response ([CR], disappearance of all evidence of disease) or Partial Response ([PR], regression of measurable disease and no new sites) per RECIST 1.1	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) assessed by the BICR as per RECIST 1.1	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first.	up to 5 years
ORR assessed by the investigator as per RECIST 1.1		up to 2 years
PFS assessed by the investigator as per RECIST 1.1		up to 5 years
Duration of response (DoR) assessed by the BICR and the investigator as per RECIST 1.1	DoR is defined as the time from the date of first achievement of CR or PR (whichever is documented first) to the date of the first documentation of PD or death (whichever occurs first)	up to 2 years
Overall survival (OS)	OS is defined as the time from randomization to death due to any cause.	up to 5 years
Adverse Events (AEs)	Incidence and severity of AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE) v6.0.	time from the date of the first dose of study drug until 90 days after last dose, assessed up to 5 years

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): October 31, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): December 4, 2029

Study Registration Dates

• First Submitted: September 13, 2026
• First Submitted That Met QC Criteria: September 13, 2026
• First Posted (Actual): September 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 13, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Alkaloids; Indoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Deoxyribonucleosides; Fluorouracil; Docetaxel; Trastuzumab; Capecitabine; Vinorelbine; Paclitaxel; eribulin
• Other Study ID Numbers: HLX22-BC202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No