Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: CYH33 + fulvestrant Participants will receive CYH33 in combination with a standard fixed dose of fulvestrant 500 mg. |
Drug: CYH33
Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.
Drug: Fulvestrant
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.
|
Experimental: CYH33 + fulvestrant + palbociclib Participants will receive CYH33 in combination with standard fixed dose of fulvestrant (500 mg) and palbociclib (125 mg). |
Drug: CYH33
Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.
Drug: Fulvestrant
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.
Drug: Palbociclib
Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle.
|
Experimental: CYH33 + letrozole + palbociclib Participants will receive CYH33 in combination with standard fixed dose of letrozole (2.5 mg) and palbociclib (125 mg) |
Drug: CYH33
Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.
Drug: Letrozole
Participants will receive oral letrozole once daily continuous on Day 1-28 of each cycle.
Drug: Palbociclib
Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle.
|
Outcome Measures
Primary Outcome Measures
- Dose Limiting Toxicities (DLT) [28 days]
Incidence rate of DLT in the first cycle (of 28 days).
Secondary Outcome Measures
- 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
- Pharmacokinetic measures - Tmax [20 months]
Measure of time to reach maximum (peak) plasma concentration
- 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.
- Assess the changes of biomarker-KRAS [20 months]
Pre- and post-treatment KRAS changes in ctDNA samples.
Eligibility Criteria
Criteria
Main Inclusion Criteria:
-
Provide informed consent voluntarily.
-
Male and female patients ≥ 18 years of age.
-
Patient must have a histologically or cytologically documented locally advanced, recurrent or metastatic breast cancer.
-
In case of women, both premenopausal and postmenopausal patients can be enrolled in the study.
-
Confirmed diagnosis of HR+, HER2- breast cancer.
-
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.
-
Patient must have evidence of disease radiological progression after previous endocrine therapy, or other systemic therapy.
-
Patient has measurable disease per RECIST v1.1.
-
ECOG ≤ 1.
-
Patient must have adequate organ and bone marrow function.
Main Exclusion Criteria:
-
Previously received any anticancer therapy within 28 days or 5 times of half-lives prior to the first dose of the study treatment.
-
Previously received treatment with any PI3Kα inhibitor, AKT inhibitor, or mTOR inhibitor.
-
Radical radiation therapy within 4 weeks prior to the first dose of the study treatment.
-
Patient with an established diagnosis of diabetes mellitus.
-
Any other concurrent disease with potential risk of insulin resistance or current use of medication with potential risk of insulin resistance.
-
Patient with clinically significant cardiovascular disease.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Haihe Biopharma Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CYH33-G103