Combination treatment of HS-10352 and fulvestrant for advanced breast cancer

A Phase Ib, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10352 in Combination With Fulvestrant in Patients With Hormone Receptor (HR) Positive, Human Epidermal Growth Factor 2 (HER2)-Negative, PIK3CA Mutation, Locally Advanced or Metastatic Breast Cancer

This study is testing a new combination treatment of HS-10352 and fulvestrant to see if it can help people with advanced breast cancer that has specific genetic changes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 224 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05504213 on ClinicalTrials.gov

What this trial studies

This Phase Ib study evaluates the safety, tolerability, pharmacokinetics, and efficacy of HS-10352, a selective inhibitor of phosphoinositide 3-kinase, in combination with fulvestrant for patients with hormone receptor positive, HER2-negative advanced breast cancer that has PIK3CA mutations. The study is conducted in two stages: the first stage focuses on dose escalation to determine the maximum tolerable dose, while the second stage expands on this to further assess efficacy and establish the recommended phase 2 dose. Participants will be monitored for adverse events and disease progression throughout the study.

Who should consider this trial

Good fit: Ideal candidates include adults with HR+ HER2- advanced breast cancer that is not amenable to curative treatment and has confirmed PIK3CA mutations.

Not a fit: Patients with early-stage breast cancer or those without PIK3CA mutations are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced breast cancer harboring PIK3CA mutations.

How similar studies have performed: While this approach is novel in its specific combination, similar studies targeting PIK3CA mutations in breast cancer have shown promising results.

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.

Where this trial is running

Shanghai, Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Xichun Hu, PhD — Fudan University
• Study coordinator: Xichun Hu, PhD

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