Study of JSKN016 Combination Therapy in Inoperable Locally Advanced or Metastatic HER2-Negative Breast Cancer

Official title

The Multicenter, Open-label, Single-arm, Multi-cohort Phase Ib/II Clinical Study to Evaluate the Efficacy and Safety of JSKN016 in Combination Therapy in Chinese Participants With Inoperable Locally Advanced or Metastatic HER2-negative Breast Cancer

Overview

This study aims to evaluate the safety and effectiveness of JSKN016 in combination with different treatments for patients with HER2-negative breast cancer that cannot be removed by surgery or has spread to other parts of the body. The study includes four groups of patients based on treatment history and tumor characteristics. Each group will receive JSKN016 with chemotherapy or immunotherapy. The goal is to find out how well the treatment works and how safe it is.

Detailed description

This clinical study investigates the safety and efficacy of JSKN016 combined with various therapies for patients with advanced, inoperable, or metastatic HER2-negative breast cancer. The study includes four groups with different treatment regimens, targeting HR+HER2-negative breast cancer and triple-negative breast cancer (TNBC) with varying prior treatments. Participants will receive JSKN016 in combination with paclitaxel, capecitabine, eribulin, or pembrolizumab. The primary endpoint is the objective response rate (ORR) based on RECIST 1.1 criteria. The secondary endpoints include efficacy, safet, and other related outcomes.

Interventions

• Drug JSKN016
  JSKN016 is administered via intravenous infusion at doses of 5mg/kg or 6mg/kg every 3 weeks, starting on Day 1 of each cycle. If the 5mg/kg dose is well tolerated during the safety lead-in phase, the dose may be increased to 6mg/kg for subsequent cycles.
• Drug Capecitabine
  The drug is administered orally at a dose of 1000mg/m², twice daily for two weeks, followed by a one-week break. Treatment cycles repeat every three weeks.
• Drug Paclitaxel (albumin bound)
  The drug is administered intravenously at a dose of 125mg/m², with infusions on Day 1 and Day 8 of each treatment cycle. The treatment cycle is repeated every 3 weeks.
• Drug Eribulin
  The drug is administered intravenously at a dose of 1.4mg/m², with infusions on Day 1 and Day 8 of each treatment cycle. The treatment cycle is repeated every 3 weeks.
• Drug Pembrolizumab
  The drug is administered intravenously at a fixed dose of 200mg, with infusions on Day 1 of each 3-week treatment cycle.

Primary outcome measures

• Objetctive Response Rate (ORR) [Time frame: From baseline until disease progression, death, or end of treatment, whichever occurs first (up to approximately 24 months)]

Secondary outcome measures (5)

• Duration of Response (DoR) [Time frame: From first documented response to progression or death (up to approximately 24 months)]
• Disease Control Rate (DCR) [Time frame: From baseline to disease progression or end of treatment (up to approximately 24 months)]
• Progression-Free Survival (PFS) [Time frame: From first dose until disease progression or death (up to approximately 24 months)]
• Overall Survival (OS) [Time frame: From first dose to death (up to approximately 36 months)]
• Frequency and Severity of Adverse Events (AEs) [Time frame: From first dose through 30 days after the last dose of study treatment (up to approximately 30 months)]

Eligibility criteria

Inclusion criteria

• Capable of understanding and signing the informed consent form.
• Aged ≥18 and ≤75 years, regardless of sex.
• Histologically or cytologically confirmed inoperable locally advanced or metastatic HER2-negative breast cancer.
• Hormone receptor-positive participants with progression/intolerance after standard endocrine therapy, or unsuitable for it.
• Disease progression confirmed by radiological evidence post-systemic treatment.
• Available archived or newly obtained tumor tissue/biopsy.
• No prior systemic therapy for advanced disease, except for prior endocrine ± targeted therapy or CDK4/6 inhibitors.
• Measurable non-CNS lesion per RECIST 1.1.
• Expected survival ≥3 months.
• ECOG performance status of 0 or 1.
• Contraceptive use agreement for fertile participants.
• Adequate organ function within 7 days of enrollment:

• Bone marrow: ANC ≥1.5 × 10⁹/L, Hemoglobin ≥90 g/L, Platelets ≥100 × 10⁹/L.
• Liver: Bilirubin ≤1.5 × ULN, ALT/AST ≤3 × ULN.
• Renal: Creatinine ≤1.5 × ULN or Ccr ≥60 mL/min.
• Coagulation: INR/PT ≤1.5 × ULN, APTT ≤1.5 × ULN.
• LVEF ≥50%.

Exclusion criteria

• CNS metastasis (except stable cases treated with radiation or surgery).
• Unstable spinal cord compression or untreated history.
• Recent live vaccine (except seasonal flu vaccines).
• Recent anti-tumor treatment within 28 days or 5 half-lives (whichever is shorter).
• Recent palliative therapy within 14 days.
• Major surgery within 28 days or planned during the study.
• Severe gastrointestinal issues or recent major GI bleeding.
• Uncontrolled pleural/peritoneal effusions or cachexia.
• Prior HER3/TROP2-targeted therapy or topoisomerase I inhibitors.
• Other malignancies within 5 years (except certain skin or localized cancers).
• Current interstitial lung disease or uncontrolled infections.
• Severe hypercalcemia or uncontrolled cancer-related pain.
• Autoimmune diseases, unless stable with treatment.
• Uncontrolled comorbidities (e.g., active infections, cardiovascular issues).
• Toxicities from previous treatments not resolved to CTCAE ≤1.
• Recent steroid use or need for systemic immunosuppressive therapy.
• Allergy to study drug components.
• Pregnancy or breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer center — Shanghai

Identifiers

NCT: NCT06942234 · JSKN016-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗