Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer

Haihe Biopharma Co., Ltd.228 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

228

Conditions

Advanced Breast Cancer

Interventions

CYH33

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Dose Limiting Toxicities (DLT)

Incidence rate of DLT in the first cycle (of 28 days).

Time frame: 28 days

Secondary Outcomes

Safety and tolerability

Type, incidence, duration, severity and seriousness of adverse events (AEs).

Time frame: 30 months

Preliminary efficacy-ORR

Tumor objective response rate (ORR) assessed by RECIST v1.1

Time frame: 30 months

Preliminary efficacy-CBR

Clinical benefit rate (CBR) assessed by RECIST v1.1

Time frame: 30 months

Preliminary efficacy-PFS

Progression Free Survival (PFS) assessed by RECIST v1.1

Time frame: 30 months

Pharmacokinetic measures - AUC

Measure the variation of concentration in blood plasma as a function of time

Time frame: 20 months

Pharmacokinetic measures - C trough

Measure the minimum (trough) plasma concentration

Time frame: 20 months

Pharmacokinetic measures - Cmax

Measure the maximum (peak) plasma concentration

Time frame: 20 months

Pharmacokinetic measures - Tmax

Measure of time to reach maximum (peak) plasma concentration

Time frame: 20 months

Pharmacokinetic measures - CL/F

Measure apparent total clearance(s) from plasma after administration

Time frame: 20 months

Pharmacokinetic measures - Vz/F

Measure apparent volume of distribution during terminal phase

Time frame: 20 months

Assess downstream effects of PI3K pathway inhibition on blood glucose

Pre- and post-treatment of blood glucose

Time frame: 20 months

Assess downstream effects of PI3K pathway inhibition on C peptide

Pre- and post-treatment of C peptide

Time frame: 20 months

Assess the changes of biomarker-PIK3CA

Pre- and post-treatment PIK3CA changes in ctDNA samples.

Time frame: 20 months

Assess the changes of biomarker-PTEN

Pre- and post-treatment PTEN changes in ctDNA samples.

Time frame: 20 months

Assess the changes of biomarker-KRAS

Pre- and post-treatment KRAS changes in ctDNA samples.

Time frame: 20 months

Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts