A Study to Evaluate HLX22 in Combination With HLX87 in Patients With HER2-Positive Recurrent or Metastatic Breast Cancer

The study consists of two stages Stage I is an open-label, multicenter, randomized, parallel-controlled phase II clinical study, and its primary objective is to evaluate the clinical efficacy of HLX22 in combination with HLX87 as first-line treatment in patients with HER2-positive recurrent or metastatic breast cancer based on ORR and PFS results.

Stage II is an open-label, multicenter, randomized, parallel-controlled phase III clinical study, and its primary objective is to evaluate the clinical efficacy of HLX22 in combination with HLX87 as first-line treatment in patients with HER2-positive recurrent or metastatic breast cancer based on PFS results.

Inclusion criteria

• 1. Have a full understanding of the study content, and sign the informed consent form (ICF); 2. Aged ≥ 18 years at the time of signing the ICF, male or female; 3. Histopathologically confirmed breast cancer that meets the following criteria:

• Advanced or metastatic breast cancer.
• HER2-positive as determined by the central laboratory, defined as IHC 3+, or IHC 2+ and ISH+.
• Positive or negative for hormone receptor HR (including estrogen receptor [ER] and progesterone receptor [PgR]) as determined by the central laboratory 4. No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer (1 line of endocrine therapy is allowed).

• At least one measurable lesion as assessed by central imaging according to RECIST v1.1.

• Eastern Cooperative Oncology Group performance status score within 7 days prior to the first dose of study drugs: 0-1.

• Life expectancy ≥ 12 weeks. 9. Adequate organ functions

Exclusion criteria

• 1. History of a second malignancy within 3 years prior to signing the ICF. 2. Previous use of doxorubicin with a concentration of > 360 mg/m2 (or equivalent).

• Prior treatment with ADCs including exatecan derivatives that contain topoisomerase I inhibitors.

• Uncontrolled or significant cardiovascular diseases 5. Cerebrovascular accidents within 6 months prior to the first dose of study drugs.

• ILD/pneumonitis, or suspected ILD/pneumonitis or clinically significant lung-specific intercurrent illness .

• Active infection . 8. Presence of spinal cord compression or clinically symptomatic central nervous system metastases.

• Residual toxicity from previous anti-tumor therapy that has not resolved to Grade ≤ 1 as per NCI-CTCAE V6.0 or baseline level (except for alopecia).

• Presence of active tuberculosis. 11. Have received treatment with live attenuated vaccines within 30 days prior to the first dose of study drugs.

• Known history of severe allergic reaction to macromolecular protein preparations, hypersensitivity to the ingredient of the investigational products, or severe hypersensitivity to any excipient of the study drugs.

• Known history of abuse of psychotropic drugs or drug addiction. 14. Pregnant or lactating women.