A Phase Ib Study of HS-10352 Plus Fulvestrant in Patients With Advanced Breast Cancer

NCT ID: NCT05504213

Last Updated: 2022-08-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-12
• Study Completion Date: 2025-12-31

Brief Summary

HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide 3-kinase (p110α). The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of HS-10352 plus fulvestrant in patients with hormone receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast cancer (ABC) harboring PIK3CA mutations.

Detailed Description

This is a Phase Ib open-label, 2-Part, multi-center study in China. The study will be conducted in two stages: Stage 1 is the dose-escalation part, which is designed to evaluate the safety, tolerability, PK and efficacy, as well as to determine the maximum tolerable dosage (MTD) or maximum applicable dose (MAD) of HS-10352 in combination with fulvestrant. Stage 2 is the dose-expansion part, which is aimed to further assess the efficacy, safety, tolerability and PK, and to establish the recommended phase 2 dose (RP2D) of HS-10352 in combination with fulvestrant.

All participants will be carefully monitored for adverse events (AE) during the study treatment and for 28 days after the last dose of study drug. The PK characteristics of HS-10352 and fulvestrant will be evaluated from C1 to C6. Subjects of this study will be assessed for progression once every 8 weeks until objective disease progression or withdrawal from the trial. As the disease progresses, survival follow-up is recommended bimonthly.

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Endocrine therapy-resistant (Stage 1)

Participants who are endocrine therapy pre-treated will be administrated at escalating doses orally of HS-10352 in combination with fulvestrant (500 mg, intramuscular).

Group Type: EXPERIMENTAL

HS-10352 combined with fulvestrant (Stage 1)

Intervention Type: DRUG

Drug: HS-10352 HS-10352 will be administered at escalating doses orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 (C1D1) in a 28 day cycle.

Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Cohort 2: Endocrine therapy-resistant (Stage 2)

Participants who are endocrine therapy-resistant will be treated with HS-10352 orally at the MTD/MAD identified in Stage 1 or/and lower dose in combination with fulvestrant (500 mg, intramuscular)

Group Type: EXPERIMENTAL

HS-10352 combined with fulvestrant (Stage 2)

Intervention Type: DRUG

Drug: HS-10352 participants will be enrolled into Cohort 2 (endocrine therapy-resistant) and Cohort 3 (endocrine therapy-sensitive or naïve) respectively and HS-10352 will be administered at the recommended dose identified in Part 1.

Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Cohort 3: Endocrine therapy-sensitive or endocrine-naïve (Stage 2)

Participants who are endocrine therapy-sensitive or naïve will be treated with HS-10352 orally at MTD/MAD or/and lower dose identified in Stage 1 in combination with fulvestrant (500 mg, intramuscular)

Group Type: EXPERIMENTAL

HS-10352 combined with fulvestrant (Stage 2)

Intervention Type: DRUG

Drug: HS-10352 participants will be enrolled into Cohort 2 (endocrine therapy-resistant) and Cohort 3 (endocrine therapy-sensitive or naïve) respectively and HS-10352 will be administered at the recommended dose identified in Part 1.

Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Interventions

HS-10352 combined with fulvestrant (Stage 1)

Drug: HS-10352 HS-10352 will be administered at escalating doses orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 (C1D1) in a 28 day cycle.

Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Intervention Type: DRUG

HS-10352 combined with fulvestrant (Stage 2)

Drug: HS-10352 participants will be enrolled into Cohort 2 (endocrine therapy-resistant) and Cohort 3 (endocrine therapy-sensitive or naïve) respectively and HS-10352 will be administered at the recommended dose identified in Part 1.

Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Men or women aged more than or equal to (≥) 18 years

2. HR+ HER2- breast cancer confirmed by histology or cytology.

3. Locally advanced disease not amenable to curative treatment by surgery or metastatic disease.

4. Have adequate tumor tissue for the analysis of PIK3CA mutational status. At dose expansion stage, participants should be identified as PIK3CA-mutation positive before enrollment.

5. Females should have postmenopausal status due to either surgical/natural menopause or ovarian suppression with a luteinizing hormone releasing hormone (LHRH) agonist before enrollment. Males should be pre-treated with a LHRH agonist.

6. Have either measurable disease per RECIST v1.1 criteria or at least one predominantly lytic bone lesion must be present.

7. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.

8. Estimated life expectancy for at least three months

9. Females should be using adequate contraceptive measures and should not be breastfeeding at the time of screening, during the study and until 6 months after completion of the study; and have negative results of blood pregnancy test prior to C1D1.

Males should be using adequate contraceptive measures at the time of screening, during the study and until 6 months after completion of the study.

10. Have signed Informed Consent Form

11. Dose escalation stage-Cohort 1: subjects resistant to endocrine therapy Dose expansion stage-Cohort 2: subjects resistant to endocrine therapy Dose expansion stage-Cohort 3: endocrine therapy-sensitive or endocrine-naive subjects

Exclusion Criteria

1. Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment

2. Treatment with any of the following:

1. Previous or current treatment with PI3K, AKT or mTOR inhibitors

2. For expansion stage, prior treatment with fulvestrant

3. Any cytotoxic chemotherapy, investigational agents within 21 days of the first dose of study drug; anticancer drugs which have been received within 14 days before the first administration.

4. Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.

5. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.

3. With inflammatory breast cancer at screening.

4. Inadequate bone marrow reserve or organ function.

5. Uncontrolled pleural effusion or ascites or pericardial effusion.

6. Known and untreated, or active central nervous system metastases.

7. History of primary or secondary diabetes.

8. History of acute or chronic pancreatitis

9. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of HS-10352 or fulvestrant.

10. History of hypersensitivity to any active or inactive ingredient of HS-10352/ fulvestrant or to drugs with a similar chemical structure or class to HS-10352.

11. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

12. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Hansoh Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xichun Hu, PhD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xichun Hu, PhD

Role: CONTACT

xchu2009@hotmail.com

021-64175590

Jian Zhang, PhD

Role: CONTACT

syner2000@163.com

021-64175590 ext. 86500

Facility Contacts

Xichun Hu, PhD

Role: primary

xchu2009@hotmail.com

021-64175590

Jian Zhang, PhD

Role: backup

syner2000@163.com

021-64175590 ext. 86500

Other Identifiers

HS-10352-102

Identifier Type: -

Identifier Source: org_study_id