Clinical Trial of SYS6010±SYH2051 Versus Chemotherapy in Advanced Breast Cancer and Other Solid Tumors

A Phase 1b/2 Clinical Study to Evaluate the Safety and Efficacy of SYS6010 as a Monotherapy or in Combination With SYH2051 Compared to Investigator's Choice Chemotherapy in Patients With EGFR-Expressing Advanced Unresectable or Metastatic Solid Tumors, Including But Not Limited to Breast Cancer

The study consists of two phases. Phase 1b and Phase 2. Phase 1b aims to evaluate the safety, tolerability, and preliminary efficacy of SYS6010 as a monotherapy and in combination with SYH2051, and to determine the recommended Phase 2 dose (RP2D) for subsequent Phase 2 studies. Phase 2 aims to assess the efficacy and safety of SYS6010 monotherapy or in combination with SYH2051 compared to investigator-selected chemotherapy in patients with EGFR-expressing, unresectable locally advanced or metastatic advanced breast cancer.

Phase Ⅰb Design:

Group A (SYS6010 3.2 mg/kg, Q2W):

Monotherapy Cohort: Planned enrollment of 8-12 breast cancer patients to evaluate the safety and preliminary efficacy of SYS6010 monotherapy.

Combination Cohort: Includes dose-escalation and expansion phases. Dose-escalation phase: A "3+3" design will be used to explore the safety of SYS6010 combined with SYH2051, with SYH2051 doses ranging from 60-80 mg.

Expansion phase: Upon completion of dose-escalation and confirmation of safety, breast cancer patients may be enrolled in the expansion phase.

Group B (SYS6010 3.6 mg/kg, Q2W):

Monotherapy Cohort: Planned enrollment of 8-12 breast cancer patients. Combination Cohort: Similar to Group A, with SYH2051 doses ranging from 40-60 mg.

Group C (SYS6010 3.6 mg/kg, Q2W): Enroll 40 EGFR-expressing HR+/HER2- breast cancer patients to further evaluate the safety and efficacy in this specific population.

Phase Ⅱ Design:

Based on molecular subtypes of breast cancer, cohort studies will be conducted.

Each cohort will enroll 125 patients, randomized in a 2:2:1 ratio into three groups:

SYS6010 + SYH2051 SYS6010 monotherapy Chemotherapy control.

Inclusion Criteria:

• 1. Age ≥ 18 years. 2. Phase 1b/Phase 2: Breast cancer (no tumor type restriction during the combination dose escalation phase).

  3. Provide tumor tissue samples for immunohistochemical EGFR expression testing, with EGFR expression positive as confirmed by the central laboratory.

  4. At least one measurable extracranial lesion according to RECIST v1.1 criteria (no requirement during the combination dose escalation phase of Phase 1b).

  5. ECOG performance status score of 0-1. 6. Expected survival ≥ 3 months. 7. Major organ function meets the relevant laboratory test standards for hematology, renal function, liver function, and coagulation within 7 days prior to treatment.

  8. Subject agrees to use effective contraception from the time of signing the informed consent form until 6 months after the last dose.

  9. Willing to participate in the study, understand the study procedures, and sign a written informed consent form.

Exclusion Criteria:

• 1. Active central nervous system (CNS) metastases or carcinomatous meningitis. Patients with treated and stable brain metastases are eligible for inclusion.

  2. Previously diagnosed HER2-positive breast cancer (IHC 3+ or ISH positive) (Applicable to Phase 1b Group C and Phase 2).

  3. Previously treated with antibody-drug conjugates (ADC) containing topoisomerase I inhibitors (Applicable to Phase 1b Group C and Phase 2).

  4. Allergy to any component of SYS6010 or SYH2051, or to humanized monoclonal antibodies.

  5. Allergy to any component of SYS6010 or SYH2051, or to humanized monoclonal antibodies (This is a repeat of criteria #4).

  6. Adverse events from prior antitumor therapy not recovered to ≤ Grade 1 (unless the investigator deems there is no safety risk).

  7. Failure to meet the required washout period for prior medications or treatments as specified in the protocol.

  8. History of severe cardiovascular or cerebrovascular diseases. 9. History of interstitial lung disease (ILD) / non-infectious pneumonia, or current ILD/non-infectious pneumonia, or imaging findings at screening that cannot rule out these conditions.

  10. Thyroid dysfunction requiring medication, unless the condition is controlled by medication and no dose adjustments are needed.

  11. Severe infection within 4 weeks prior to the first use of the investigational drug.

  12. History of discontinuing EGFR-targeted therapy for ≥ 1 month due to skin toxicity, or current skin conditions requiring medication.

  13. Gastrointestinal diseases or functional impairments that may significantly affect the absorption of the investigational drug (e.g., ulcerative disease, severe nausea/vomiting, diarrhea, malabsorption, etc.).

  14. Uncontrolled pleural or peritoneal effusion. 15. Active HBV or HCV infection, syphilis, HIV infection, or AIDS. 16. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.