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

NCT04856371 | Unknown Phase 1

• 1 other identifier: CYH33-G103
• Study Type: interventional
• Target: 228
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Advanced Breast Cancer

Keywords

PIK3CA Mutant; Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities (DLT)

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

  28 days

Secondary Outcomes (15)

• Safety and tolerability

  30 months

• Preliminary efficacy-ORR

  30 months

• Preliminary efficacy-CBR

  30 months

• Preliminary efficacy-PFS

  30 months

• Pharmacokinetic measures - AUC

  20 months

Study Arms (3)

CYH33 + fulvestrant

EXPERIMENTAL

Participants will receive CYH33 in combination with a standard fixed dose of fulvestrant 500 mg.

Drug: CYH33; Drug: Fulvestrant

CYH33 + fulvestrant + palbociclib

EXPERIMENTAL

Participants will receive CYH33 in combination with standard fixed dose of fulvestrant (500 mg) and palbociclib (125 mg).

Drug: CYH33; Drug: Fulvestrant; Drug: Palbociclib

CYH33 + letrozole + palbociclib

EXPERIMENTAL

Participants will receive CYH33 in combination with standard fixed dose of letrozole (2.5 mg) and palbociclib (125 mg)

Drug: CYH33; Drug: Letrozole; Drug: Palbociclib

Interventions

CYH33 DRUG

Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.

CYH33 + fulvestrant; CYH33 + fulvestrant + palbociclib; CYH33 + letrozole + palbociclib

Fulvestrant DRUG

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.

CYH33 + fulvestrant; CYH33 + fulvestrant + palbociclib

Letrozole DRUG

Participants will receive oral letrozole once daily continuous on Day 1-28 of each cycle.

CYH33 + letrozole + palbociclib

Palbociclib DRUG

Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle.

CYH33 + fulvestrant + palbociclib; CYH33 + letrozole + palbociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Haihe Biopharma Co., Ltd.: lead

MeSH Terms

Interventions

CYH33; Fulvestrant; Letrozole; palbociclib

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Yong Yuan, MD

CONTACT

86 13820384005; yong.yuan@haihepharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2021
• First Posted: April 23, 2021
• Study Start: April 1, 2021
• Primary Completion: March 1, 2022
• Study Completion: December 1, 2022
• Last Updated: April 23, 2021

Record last verified: 2021-03