Clinical trial NCT04856371: Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer
Official title: A Multicenter, Open-label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Breast Cancer
Keywords: PIK3CA Mutant
Advanced Breast Cancer
Lead sponsor: Haihe Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-23
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, phase Ib study designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CYH33 administered orally in combination with standard-of-care ET ± CDK4/6 inhibitor therapies for the treatment of locally advanced, recurrent or metastatic hormone-receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Patients will be enrolled in two stages, including dose exploration phase (Stage 1) and dose expansion phase (Stage 2) of each cohort.


Eligibility criteria: Main Inclusion Criteria:

1. Provide informed consent voluntarily.
2. Male and female patients ≥ 18 years of age.
3. Patient must have a histologically or cytologically documented locally advanced, recurrent or metastatic breast cancer.
4. In case of women, both premenopausal and postmenopausal patients can be enrolled in the study.
5. Confirmed diagnosis of HR+, HER2- breast cancer.
6. For Stage 1 dose exploration phase, patients with or without PIK3CA mutation may be enrolled; For Stage 2 dose expansion phase, patients with PIK3CA mutations are required.
7. Patient must have evidence of disease radiological progression after previous endocrine therapy, or other systemic therapy.
8. Patient has measurable disease per RECIST v1.1.
9. ECOG ≤ 1.
10. Patient must have adequate organ and bone marrow function.

Main Exclusion Criteria:

1. Previously received any anticancer therapy within 28 days or 5 times of half-lives prior to the first dose of the study treatment.
2. Previously received treatment with any PI3Kα inhibitor, AKT inhibitor, or mTOR inhibitor.
3. Radical radiation therapy within 4 weeks prior to the first dose of the study treatment.
4. Patient with an established diagnosis of diabetes mellitus.
5. Any other concurrent disease with potential risk of insulin resistance or current use of medication with potential risk of insulin resistance.
6. Patient with clinically significant cardiovascular disease.

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: 28 days
Secondary outcomes:
measure: Safety and tolerability
timeFrame: 30 months
measure: Preliminary efficacy-ORR
timeFrame: 30 months
measure: Preliminary efficacy-CBR
timeFrame: 30 months
measure: Preliminary efficacy-PFS
timeFrame: 30 months
measure: Pharmacokinetic measures - AUC
timeFrame: 20 months
measure: Pharmacokinetic measures - C trough
timeFrame: 20 months
measure: Pharmacokinetic measures - Cmax
timeFrame: 20 months
measure: Pharmacokinetic measures - Tmax
timeFrame: 20 months
measure: Pharmacokinetic measures - CL/F
timeFrame: 20 months
measure: Pharmacokinetic measures - Vz/F
timeFrame: 20 months
measure: Assess downstream effects of PI3K pathway inhibition on blood glucose
timeFrame: 20 months
measure: Assess downstream effects of PI3K pathway inhibition on C peptide
timeFrame: 20 months
measure: Assess the changes of biomarker-PIK3CA
timeFrame: 20 months
measure: Assess the changes of biomarker-PTEN
timeFrame: 20 months
measure: Assess the changes of biomarker-KRAS
timeFrame: 20 months
Other outcomes:
Locations:
Study officials:
References: