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

Advanced Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04856371
• Other study ID #: CYH33-G103
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 2021
• Est. completion date: December 2022

Study information

• Verified date: March 2021
• Source: Haihe Biopharma Co., Ltd.
• Contact: Yong Yuan, MD
• Phone: 86 13820384005
• Email: yong.yuan[@]haihepharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 228
• Est. completion date: December 2022
• Est. primary completion date: March 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 PI3Ka 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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• CYH33
Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.
• 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.
• Letrozole
Participants will receive oral letrozole once daily continuous on Day 1-28 of each cycle.
• Palbociclib
Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Haihe Biopharma Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLT)	Incidence rate of DLT in the first cycle (of 28 days).	28 days
Secondary	Safety and tolerability	Type, incidence, duration, severity and seriousness of adverse events (AEs).	30 months
Secondary	Preliminary efficacy-ORR	Tumor objective response rate (ORR) assessed by RECIST v1.1	30 months
Secondary	Preliminary efficacy-CBR	Clinical benefit rate (CBR) assessed by RECIST v1.1	30 months
Secondary	Preliminary efficacy-PFS	Progression Free Survival (PFS) assessed by RECIST v1.1	30 months
Secondary	Pharmacokinetic measures - AUC	Measure the variation of concentration in blood plasma as a function of time	20 months
Secondary	Pharmacokinetic measures - C trough	Measure the minimum (trough) plasma concentration	20 months
Secondary	Pharmacokinetic measures - Cmax	Measure the maximum (peak) plasma concentration	20 months
Secondary	Pharmacokinetic measures - Tmax	Measure of time to reach maximum (peak) plasma concentration	20 months
Secondary	Pharmacokinetic measures - CL/F	Measure apparent total clearance(s) from plasma after administration	20 months
Secondary	Pharmacokinetic measures - Vz/F	Measure apparent volume of distribution during terminal phase	20 months
Secondary	Assess downstream effects of PI3K pathway inhibition on blood glucose	Pre- and post-treatment of blood glucose	20 months
Secondary	Assess downstream effects of PI3K pathway inhibition on C peptide	Pre- and post-treatment of C peptide	20 months
Secondary	Assess the changes of biomarker-PIK3CA	Pre- and post-treatment PIK3CA changes in ctDNA samples.	20 months
Secondary	Assess the changes of biomarker-PTEN	Pre- and post-treatment PTEN changes in ctDNA samples.	20 months
Secondary	Assess the changes of biomarker-KRAS	Pre- and post-treatment KRAS changes in ctDNA samples.	20 months