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.

NCT07618390 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: SYSKY-2026-061-01
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Breast Cancer

Keywords

breast cancer; PIK3CA-mutant; HER2-negative; HR-positive

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-free survival (PFS), defined as the time from initiation of the first study treatment to the first occurrence of disease progression (PD) or death from any cause, whichever occurs first, as assessed by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

  From the date of first study treatment until documented disease progression or death from any cause, whichever occurs first, assessed up to 33 months

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  From the date of first study treatment until documented disease progression or death from any cause, whichever occurs first, assessed up to 33 months

• Duration of Response (DOR)

  From the date of first study treatment until documented disease progression or death from any cause, whichever occurs first, assessed up to 33 months

• Clinical Benefit Rate (CBR)

  From the date of first study treatment until documented disease progression or death from any cause, whichever occurs first, assessed up to 33 months

Study Arms (1)

Inavolisib + Ribociclib + Fulvestrant

EXPERIMENTAL

Drug: Inavolisib + Ribociclib + Fulvestrant

Interventions

Inavolisib + Ribociclib + Fulvestrant DRUG

A total of 160 Chinese patients who meet the eligibility criteria and are confirmed to have PIK3CA-mutant breast cancer will receive the following treatment regimen: * \*\*Inavolisib:\*\* 9 mg tablet, administered orally once daily (PO QD), on Days 1-28 of each 28-day cycle, starting from Cycle 1 Day 1; * \*\*Ribociclib:\*\* 600 mg capsule or tablet, administered orally once daily (PO QD), on Days 1-21 of each 28-day cycle, starting from Cycle 1 Day 1; * \*\*Fulvestrant:\*\* 500 mg administered by intramuscular injection (IM) on Days 1 and 15 of Cycle 1, and thereafter on Day 1 of each subsequent 28-day cycle (approximately every 4 weeks).

Inavolisib + Ribociclib + Fulvestrant

Eligibility Criteria

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

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.

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.

Sponsors & Collaborators

• Novartis: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• Hoffmann-La Roche: collaborator

MeSH Terms

Conditions

Breast Neoplasms

Interventions

inavolisib; ribociclib; 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

Central Study Contacts

Jianli Zhao

CONTACT

15920589334; zhaojianii1988@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2026
• First Posted: June 1, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share