Advanced Breast Cancer
Conditions
Keywords
PIK3CA Mutant, Advanced Breast Cancer
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.
Interventions
DRUGCYH33
Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.
DRUGFulvestrant
Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1, 15 on Cycle 1 (28-day cycle) and Day 1 at each 28-day cycle thereafter.
DRUGLetrozole
Participants will receive oral letrozole once daily continuous on Day 1-28 of each cycle.
DRUGPalbociclib
Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle.
Sponsors
Haihe Biopharma Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLT) | 28 days | Incidence rate of DLT in the first cycle (of 28 days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | 30 months | Type, incidence, duration, severity and seriousness of adverse events (AEs). |
| Preliminary efficacy-ORR | 30 months | Tumor objective response rate (ORR) assessed by RECIST v1.1 |
| Preliminary efficacy-CBR | 30 months | Clinical benefit rate (CBR) assessed by RECIST v1.1 |
| Preliminary efficacy-PFS | 30 months | Progression Free Survival (PFS) assessed by RECIST v1.1 |
| Pharmacokinetic measures - AUC | 20 months | Measure the variation of concentration in blood plasma as a function of time |
| Pharmacokinetic measures - C trough | 20 months | Measure the minimum (trough) plasma concentration |
| Pharmacokinetic measures - Cmax | 20 months | Measure the maximum (peak) plasma concentration |
| Assess the changes of biomarker-KRAS | 20 months | Pre- and post-treatment KRAS changes in ctDNA samples. |
| Pharmacokinetic measures - CL/F | 20 months | Measure apparent total clearance(s) from plasma after administration |
| Pharmacokinetic measures - Vz/F | 20 months | Measure apparent volume of distribution during terminal phase |
| Assess downstream effects of PI3K pathway inhibition on blood glucose | 20 months | Pre- and post-treatment of blood glucose |
| Assess downstream effects of PI3K pathway inhibition on C peptide | 20 months | Pre- and post-treatment of C peptide |
| Assess the changes of biomarker-PIK3CA | 20 months | Pre- and post-treatment PIK3CA changes in ctDNA samples. |
| Assess the changes of biomarker-PTEN | 20 months | Pre- and post-treatment PTEN changes in ctDNA samples. |
| Pharmacokinetic measures - Tmax | 20 months | Measure of time to reach maximum (peak) plasma concentration |
Contacts
Primary ContactYong Yuan, MD
Outcome results
None listed