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

NCT05504213 | Unknown Phase 1

• 1 other identifier: HS-10352-102
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

dose-escalation; dose-expansion; advanced breast cancer; hormone receptor positive; PIK3CA gene mutation

Outcome Measures

Primary Outcomes (3)

• [Stage 1] Maximum tolerated dose (MTD) of HS-10352 in combination with fulvestrant

  MTD is defined as the previous dose level at which 2 or more out of 2\~6 subjects experienced a DLT.

  Cycle 1 (28 days)

• [Stage 1] Maximum applicable dose (MAD) of HS-10352 in combination with fulvestrant

  MAD is defined as follows: a) based on PK data, it is anticipated that at this dose level, the dose-exposure plateau has been reached, b) based on existing safety data, it is judged that dose escalation following this dose level will have a large safety risk or subject intolerance, or c) based on the PK-PD model, it suggested that the optimal target concentration of safety and efficacy has been explored.

  Cycle 1 (28 days)

• [Stage 2] Objective response rate (ORR) of HS-10352 in combination with fulvestrant

  ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

  From the date of first dose until the date of disease progression or withdrawal from study, approximately 3 years

Secondary Outcomes (20)

• [Stage 1 and Stage 2] Incidence and severity of treatment-emergent adverse events

  From Cycle 1 Day 1 (C1D1) until 28 days after the final dose. A cycle is 28 days.

• [Stage 1 and Stage 2] PK parameters: the maximum concentration (Cmax) of HS-10352

  Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days)

• [Stage 1] PK parameters: the maximum concentration (Cmax) of fulvestrant

  Cycle 1 (28 days)

• [Stage 1 and Stage 2] PK parameters: time of the maximum concentration (Tmax) of HS-10352

  Cycle 1 Day 1 (C1D1)，at the first day of Cycle 1 (each cycle is 28 days)

• [Stage 1] PK parameters: time of the maximum concentration (Tmax) of fulvestrant

  Cycle 1 (28 days)

Study Arms (3)

Cohort 1: Endocrine therapy-resistant (Stage 1)

EXPERIMENTAL

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

Drug: HS-10352 combined with fulvestrant (Stage 1)

Cohort 2: Endocrine therapy-resistant (Stage 2)

EXPERIMENTAL

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)

Drug: HS-10352 combined with fulvestrant (Stage 2)

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

EXPERIMENTAL

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)

Drug: HS-10352 combined with fulvestrant (Stage 2)

Interventions

HS-10352 combined with fulvestrant (Stage 1) 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 1: Endocrine therapy-resistant (Stage 1)

HS-10352 combined with fulvestrant (Stage 2) 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 2: Endocrine therapy-resistant (Stage 2); Cohort 3: Endocrine therapy-sensitive or endocrine-naïve (Stage 2)

Eligibility Criteria

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

You may qualify if:

• Men or women aged more than or equal to (≥) 18 years
• HR+ HER2- breast cancer confirmed by histology or cytology.
• Locally advanced disease not amenable to curative treatment by surgery or metastatic disease.
• 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.
• 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.
• Have either measurable disease per RECIST v1.1 criteria or at least one predominantly lytic bone lesion must be present.
• ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.
• Estimated life expectancy for at least three months
• 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.
• Have signed Informed Consent Form
• 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

You may not qualify if:

• Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment
• Treatment with any of the following:
• Previous or current treatment with PI3K, AKT or mTOR inhibitors
• For expansion stage, prior treatment with fulvestrant
• 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.
• 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.
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.
• With inflammatory breast cancer at screening.
• Inadequate bone marrow reserve or organ function.
• Uncontrolled pleural effusion or ascites or pericardial effusion.
• Known and untreated, or active central nervous system metastases.
• History of primary or secondary diabetes.
• History of acute or chronic pancreatitis
• Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of HS-10352 or fulvestrant.
• 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.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

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

Study Officials

• Xichun Hu, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xichun Hu, PhD

CONTACT

021-64175590; xchu2009@hotmail.com

Jian Zhang, PhD

CONTACT

021-64175590; syner2000@163.com

Study Design

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

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: August 17, 2022
• Study Start: January 12, 2022
• Primary Completion: July 31, 2023
• Study Completion: December 31, 2025
• Last Updated: August 17, 2022

Record last verified: 2022-05

Locations

CN (1)