A Phase ll, Interventional, Single-arm Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib and Fulvestrant in Chinese Patients With PIK3CA-mutant, HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer.

Starting soon · Phase 2

Conditions studied: Breast Cancer

In brief

This is a prospective, multicenter, open-label, single-arm phase II investigator-initiated study designed to evaluate the efficacy and safety of inavolisib in combination with ribociclib and fulvestrant as first-line treatment in Chinese patients with PIK3CA-mutant, hormone receptor-positive (HR+), HER2-negative (HER2-), endocrine-resistant metastatic breast cancer (mBC). Approximately 160 patients will be enrolled at around 16 centers in China. The study consists of a screening period of up to 28 days, a treatment period, and a post-treatment follow-up period. PIK3CA mutation status must be determined in blood or tumor tissue using polymerase chain reaction (PCR)-based assays or next-generation sequencing (NGS) performed in a local clinical laboratory. Patients with locally confirmed PIK3CA mutations who meet all eligibility criteria will be enrolled and receive study treatment with inavolisib, ribociclib, and fulvestrant. Details of the treatment regimen are provided in the Study Treatment section. Study treatment will continue until radiologically confirmed disease progression as determined by the investigator, unacceptable toxicity, withdrawal of informed consent, or study termination, whichever occurs first. Patients must have measurable disease according to RECIST v1.1. Patients with bone-only metastases are not eligible, even if the lesions are considered measurable. Locally advanced disease must be unsuitable for surgical resection or other local treatment with curative intent.

Key facts

Study ID

NCT07618390

Run by

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

People needed

160

Starts

2026-06-01

Expected to finish

2028-12-01

Last updated by the study team

2026-06-01

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Patients must meet all of the following criteria:
• Signed informed consent form (ICF).
• Female, aged ≥18 years at the time of signing the ICF.
• Must meet one of the following definitions of postmenopausal status:
• Age ≥60 years; OR
• Age <60 years with amenorrhea for ≥12 consecutive months in the absence of oral contraceptives, hormone replacement therapy, or gonadotropin-releasing hormone (GnRH) agonists/antagonists, and with follicle-stimulating hormone (FSH) and plasma estradiol levels in the postmenopausal range per local laboratory assessment; OR
• Documented bilateral oophorectomy performed ≥14 days before Cycle 1 Day 1 (first treatment), with recovery to baseline status.
• For premenopausal or perimenopausal women (i.e., those not meeting postmenopausal criteria), the following is also required:
• Ongoing treatment with a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin or leuprorelin) initiated at least 2 weeks before Cycle 1 Day 1 and continued throughout study treatment.
• Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and not amenable to curative surgery or radiotherapy.
• Estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive tumor per ASCO/CAP guidelines, defined as ≥1% of tumor cells showing positive staining on the most recent tumor biopsy.
• HER2-negative per ASCO/CAP guidelines, defined as: HER2 IHC score 0 or 1+, or IHC 2+ with negative ISH (FISH/CISH/SISH), or HER2/CEP17 ratio <2.0 on the most recent biopsy, based on local laboratory assessment.
• Biomarker eligibility: PIK3CA mutation status must be determined by PCR or NGS testing of blood or tumor tissue at a local or regional laboratory. Blood samples should represent metastatic disease and be collected after the most recent anticancer therapy; tumor tissue should preferably be from metastatic lesions.
• Disease progression during or within 12 months after completion of adjuvant endocrine therapy (aromatase inhibitor or tamoxifen). If CDK4/6 inhibitor was used in neoadjuvant/adjuvant setting, time from completion of CDK4/6 inhibitor to progression must be >12 months.
• At least one measurable lesion per RECIST v1.1. Patients with only bone metastases are not eligible, even if lesions are measurable.
• Women of childbearing potential must agree to abstinence or use effective non-hormonal contraception (failure rate <1% per year) during treatment and for specified post-treatment periods (depending on study drug), and must not donate oocytes.
• ECOG performance status 0-1.
• Life expectancy >6 months.
• Adequate hematologic and organ function within 14 days prior to treatment initiation, including:
• ANC ≥1500/μL Hemoglobin ≥9 g/dL Platelets ≥100,000/μL Fasting glucose <126 mg/dL and HbA1c <6.0% Total bilirubin ≤1.5×ULN (≤3×ULN for Gilbert syndrome) Albumin ≥2.5 g/dL AST/ALT ≤2.5×ULN (≤5×ULN with liver metastases) ALP ≤2.5×ULN (≤5×ULN with liver/bone metastases) Creatinine clearance ≥60 mL/min (Cockcroft-Gault) INR <1.5×ULN and aPTT <1.5×ULN (with specified exceptions for anticoagulation)
• Ability and willingness to comply with study procedures as judged by the investigator.

You may not qualify if…

• Metaplastic breast carcinoma.
• Any history of leptomeningeal disease or carcinomatous meningitis.
• Prior systemic therapy for metastatic breast cancer (mBC).
• Prior treatment with fulvestrant or other selective estrogen receptor degraders (SERDs), except neoadjuvant use ≤6 months.
• Prior exposure to PI3K, AKT, or mTOR inhibitors, or any drugs targeting the PI3K-AKT-mTOR pathway.
• Requirement for cytotoxic chemotherapy at study entry (e.g., visceral crisis as per local guidelines).
• Type 2 diabetes requiring ongoing systemic treatment at enrollment, or history of type 1 diabetes.
• Inability or unwillingness to take oral medication or receive intramuscular injections.
• Malabsorption syndrome or any condition affecting gastrointestinal absorption.
• Untreated or active CNS metastases (progressive disease or requiring anticonvulsants or corticosteroids for symptom control).
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage more frequently than every 2 weeks.
• Severe infection requiring intravenous antibiotics within 7 days prior to enrollment.
• Any concurrent ocular or intraocular disease requiring intervention during the study to prevent or treat potential vision loss.
• Active inflammatory or infectious ocular disease, or history of autoimmune/idiopathic uveitis.
• Requirement for daily supplemental oxygen therapy.
• Symptomatic active pulmonary disease, including pneumonia.
• Active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), or current immunosuppressive treatment for such disease.
• Any active intestinal inflammation, including diverticulitis.
• Symptomatic hypercalcemia requiring ongoing bisphosphonate or denosmab therapy.
• Clinically significant active liver disease, including severe hepatic impairment (Child-Pugh B/C), viral hepatitis, cirrhosis, or current alcohol abuse.
• Known HIV infection.
• Any severe, uncontrolled systemic disease (e.g., significant cardiopulmonary, metabolic, or infectious disease) that may affect study safety or interpretation.
• Anticancer therapy within 2 weeks prior to first dose.
• Investigational drug use within 4 weeks prior to first dose.
• Prior irradiation of ≥25% of bone marrow, or prior stem cell/bone marrow transplantation.

Full record on ClinicalTrials.gov

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