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

NCT06775236 | Not Yet Recruiting Phase 1

• 1 other identifier: SYS6010-008
• Study Type: interventional
• Target: 410
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Advanced Solid Tumors; Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity(DLT) occurrence and incidence

  The occurrence and incidence of dose-limiting toxicities (DLTs) will be assessed based on predefined criteria during the first 28 days after the initial dose. DLTs are defined as adverse events related to the study drug that meet the protocol-specified criteria for dose limitation.

  Up to approximately 3 months after the first participant is enrolled

• Adverse events (AE) occurrence and incidence

  The occurrence and incidence of adverse events (AEs) will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. AEs will be monitored from the first dose until the safety follow-up period.

  Up to approximately 36 months after the first participant is enrolled

• Objective response rate (ORR) per RECIST v1.1

  The objective response rate (ORR) will be assessed based on RECIST v1.1 criteria. ORR is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) as the best overall response.

  Up to approximately 36 months after the first participant is enrolled

Secondary Outcomes (7)

• Disease control rate (DCR) per RECIST 1.1

  Up to approximately 36 months after the first participant is enrolled

• Duration of response (DoR) per RECIST 1.1

  Up to approximately 36 months after the first participant is enrolled

• Progression free survival (PFS) per RECIST 1.1

  Up to approximately 36 months after the first participant is enrolled

• Overall survival(OS)

  Up to approximately 36 months after the first participant is enrolled

• PK parameters of toxin-bound antibody

  Up to approximately 36 months after the first participant is enrolled

Study Arms (3)

SYS6010 injection

EXPERIMENTAL

SYS6010 injection 3.2 mg/kg or 3.6 mg/kg, intravenous drip, Q2W

Drug: SYS6010 jnjection

SYS6010 injection + SYH2051 tablets

EXPERIMENTAL

SYS6010 injection 3.2 mg/kg intravenous drip + SYH2051 60 or 80 mg, oral, Q2W Or SYS6010 injection 3.6 mg/kg intravenous drip + SYH2051 40 or 60 mg, oral, Q2W

Drug: SYS6010 jnjection; Drug: SYH2051 tablets

Monotherapy Chemotherapy Group

ACTIVE COMPARATOR

Investigator's choice of monotherapy chemotherapy （Eribulin, Capecitabine, Gemcitabine, Vinorelbine, or Taxanes. )

Drug: monotherapy chemotherapy

Interventions

SYS6010 jnjection DRUG

SYS6010 is an antibody conjugate drug (ADC), composed of one anti-EGFR monoclonal antibody coupled to one JS1 via an enzyme specific linker

SYS6010 injection; SYS6010 injection + SYH2051 tablets

monotherapy chemotherapy DRUG

Investigator's choice of monotherapy chemotherapy (Eribulin, Capecitabine, Gemcitabine, Vinorelbine, or Taxanes.)

Monotherapy Chemotherapy Group

SYH2051 tablets DRUG

SYH2051 is a Selective ATM protein kinase inhibitor

SYS6010 injection + SYH2051 tablets

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥ 18 years. 2. Phase 1b/Phase 2: Breast cancer (no tumor type restriction during the combination dose escalation phase).
• \. Provide tumor tissue samples for immunohistochemical EGFR expression testing, with EGFR expression positive as confirmed by the central laboratory.
• \. At least one measurable extracranial lesion according to RECIST v1.1 criteria (no requirement during the combination dose escalation phase of Phase 1b).
• \. 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.
• \. Subject agrees to use effective contraception from the time of signing the informed consent form until 6 months after the last dose.
• \. Willing to participate in the study, understand the study procedures, and sign a written informed consent form.

You may not qualify if:

• \. Previously diagnosed HER2-positive breast cancer (IHC 3+ or ISH positive) (Applicable to Phase 1b Group C and Phase 2).
• \. Previously treated with antibody-drug conjugates (ADC) containing topoisomerase I inhibitors (Applicable to Phase 1b Group C and Phase 2).
• \. Allergy to any component of SYS6010 or SYH2051, or to humanized monoclonal antibodies.
• \. Allergy to any component of SYS6010 or SYH2051, or to humanized monoclonal antibodies (This is a repeat of criteria #4).
• \. Adverse events from prior antitumor therapy not recovered to ≤ Grade 1 (unless the investigator deems there is no safety risk).
• \. Failure to meet the required washout period for prior medications or treatments as specified in the protocol.
• \. 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.
• \. Thyroid dysfunction requiring medication, unless the condition is controlled by medication and no dose adjustments are needed.
• \. Severe infection within 4 weeks prior to the first use of the investigational drug.
• \. History of discontinuing EGFR-targeted therapy for ≥ 1 month due to skin toxicity, or current skin conditions requiring medication.
• \. 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.).
• \. 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.

Sponsors & Collaborators

• CSPC Megalith Biopharmaceutical Co.,Ltd.: lead

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Clinical Trials Information Group officer

CONTACT

86-0311-69085587; ctr-contact@cspc.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b: Dose escalation and expansion Phase 2: Randomized controlled trial

Study Record Dates

• First Submitted: January 1, 2025
• First Posted: January 15, 2025
• Study Start: March 20, 2025
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): January 15, 2028
• Last Updated: March 19, 2025

Record last verified: 2025-01