Overview
This is a Phase I, open-label, multi-center study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of CG-7321 capsules as monotherapy or in combination with fulvestrant in subjects with advanced solid tumors.
The study consists of:
- Part Ia (Monotherapy): Dose escalation (accelerated titration followed by 3+3 design) from 2mg to 50mg twice daily (BID), plus dose expansion cohorts in advanced solid tumors including HR+/HER2- breast cancer, ovarian cancer, gastric cancer, and other tumor types.
- Part Ib (Combination Therapy): Dose escalation of CG-7321 combined with fulvestrant in HR+/HER2- advanced breast cancer.
Description
CG-7321 is a novel oral small molecule inhibitor of cyclin-dependent kinases (CDKs), being developed for the treatment of advanced solid tumors. Preclinical studies have demonstrated potent anti-tumor activity in breast cancer, ovarian cancer, and gastric cancer models.
This Phase I study employs a dose escalation design to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of CG-7321.
Part Ia evaluates CG-7321 monotherapy with dose levels of 2mg, 6mg, 12mg, 20mg, 30mg, 40mg, and 50mg BID in a 28-day cycle. Single dosing (Cycle 0) followed by multiple dosing (Cycle 1 onwards) will be evaluated.
Part Ib evaluates CG-7321 in combination with fulvestrant in HR+/HER2- advanced breast cancer patients.
Dose expansion cohorts will further evaluate safety, PK, and preliminary efficacy at or near the RP2D in specific tumor types.
Eligible subjects include patients with histologically/cytologically confirmed advanced or metastatic solid tumors who have failed, are intolerant to, or have no effective standard therapy available, or who refuse standard treatment.
The Part Ia (monotherapy dose escalation) will be conducted first.
Eligibility
Inclusion Criteria:
- 1\. Voluntary signed informed consent and compliance with protocol requirements
- 2\. Age ≥18 years, any gender
- 3\. Life expectancy ≥12 weeks
- 4\. Eastern Cooperative Oncology Group（ECOG） performance status 0-1
- 5\. For Ia monotherapy dose escalation: patients with cytologically and/or histopathologically confirmed advanced or metastatic solid tumors who have failed, are intolerant to, or have no effective standard treatment, or who refuse standard treatment
- 6\. Voluntary provision of tumor tissue specimens (archived within 2 years or fresh tissue)
- 7\. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1（RECIST 1.1）
- 8\. Prior anticancer treatment-related toxicities resolved to ≤1 grade (except alopecia)
- 9\. Adequate organ and bone marrow function
- 10\. Negative serum pregnancy test within 7 days before first dose
- 11\. Agreement to use effective contraception from ICF signing to ≥6 months after last dose
- 12\. No breastfeeding during study and ≥6 months after last dose
- 13\. Understanding of study and voluntary written informed consent
Exclusion Criteria:
- 1\. Anticancer therapy (chemotherapy, targeted therapy, biologics, immunotherapy, radiotherapy) within 4 weeks before first dose, or participation in other interventional clinical studies (observational studies excluded)
- 2\. Strong Cytochrome P450 3A4（CYP3A4）inhibitors within 2 weeks before first dose
- 3\. Strong Cytochrome P450 2C8（CYP2C8） inhibitors within 2 weeks before first dose
- 4\. Other active malignancies within 3 years before first dose (except curable tumors treated radically)
- 5\. Primary Central Nervous System（CNS） tumors or CNS metastases that failed local treatment (stable asymptomatic CNS metastases allowed)
- 6\. Conditions affecting drug absorption or Pharmacokinetics（PK） parameters (e.g., uncontrolled nausea/vomiting, chronic diarrhea, malabsorption syndrome)
- 7\. Uncontrolled or significant cardiovascular disease,
- 8\. Active infection requiring systemic therapy within 2 weeks;
- 9\. Major surgery within 4 weeks before first dose (except minor procedures)
- 10\. Known allergy to study drug or excipients
- 11\. Mental or cognitive impairment affecting study compliance
- 12\. Known alcohol or drug dependence
- 13\. Pregnant or lactating women
- 14\. Investigator deems subject unsuitable for study participation
