A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Neoadjuvant Therapy With Inavolisib Plus Pertuzumab and Trastuzumab as Subcutaneous (PH-FDC SC) and 3-week Cycle Nab-paclitaxel for PIK3CA-mutated, HER2+, eBC

NCT07245797 | Not Yet Recruiting Phase 2

• 1 other identifier: 2509329-18
• Study Type: interventional
• Target: 164
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study consists of a screening period of 28 days, a treatment period. Local or central testing of PIK3CA mutation in blood or tumor tissue must be performed using an approved polymerase chain reaction (PCR)-based or next generation sequencing (NGS) assay at a clinical laboratory. Patients with confirmed eligibility criteria and PIK3CA mutant breast cancer will be randomized in a 1:1 ratio to receive: Neoadjuvant treatment with dual anti-HER2 blockade consisting of ready-to-use fixed-dose combination of pertuzumab and trastuzumab as subcutaneous (PH-FDC SC) formulation q3w and nab-paclitaxel (125 mg/m2 on days 1, 8, and 15) in 3-week cycle for total 6 cycles

• with inavolisib (6 cycles) or
• without inavolisib. In both study arms, treatment will be given until surgery/core-biopsy, disease progression, unacceptable toxicity, or withdrawal of consent of the patient. All patients will undergo surgery or biopsy after completing study therapy to assess pCR rate.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• pCR（ypT0/is ypN0）

  pCR (ypT0/is ypN0) is defined as the absence of microscopically residual invasive tumor cells in all resected specimens from the breast and axilla. Pathological response will be comprehensively evaluated based on all surgically resected breast and lymph node tissues. Biopsy alone is insufficient to confirm pCR; patients with no residual tumor in the biopsy should undergo surgery (otherwise, they are considered not to have achieved pCR, as are all patients for whom pCR cannot be confirmed). Patients who receive additional treatment after biopsy or without prior biopsy, regardless of the subsequent neoadjuvant treatment response, are considered not to have achieved pCR. Before surgical evaluation to confirm pCR, additional neoadjuvant treatment should be avoided after the completion of the study treatment.

  6months

Secondary Outcomes (3)

• ypT0

  6months

• ORR

  6months

• safety

  6 months

Other Outcomes (1)

• Exploratory end points

  1 year

Study Arms (2)

fixed-dose combination of pertuzumab and trastuzumab，and nab-paclitaxel with inavolisib.

EXPERIMENTAL

Drug: fixed-dose combination of pertuzumab and trastuzumab as subcutaneousformulation q3w and nab-paclitaxel in 3-week cycle for total 6 cycles with inavolisib (6 cycles) or without inavolisib.

fixed-dose combination of pertuzumab and trastuzumab，and nab-paclitaxel.

ACTIVE COMPARATOR

Drug: fixed-dose combination of pertuzumab and trastuzumab as subcutaneousformulation q3w and nab-paclitaxel in 3-week cycle for total 6 cycles with inavolisib (6 cycles) or without inavolisib.

Interventions

fixed-dose combination of pertuzumab and trastuzumab as subcutaneousformulation q3w and nab-paclitaxel in 3-week cycle for total 6 cycles with inavolisib (6 cycles) or without inavolisib. DRUG

fixed-dose combination of pertuzumab and trastuzumab as subcutaneousformulation q3w and nab-paclitaxel in 3-week cycle for total 6 cycles with inavolisib (6 cycles) or without inavolisib.

fixed-dose combination of pertuzumab and trastuzumab，and nab-paclitaxel with inavolisib.; fixed-dose combination of pertuzumab and trastuzumab，and nab-paclitaxel.

Eligibility Criteria

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

You may qualify if:

• Patients will be eligible for study participation only if they comply with the following criteria:
• Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
• Untreated, unilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed.
• Tumor lesion in the breast must be measurable in two dimensions, preferably by sonography.
• Patients must be in the following stages of disease:
• cT1b - cT3 regardless of nodal status. In patients with multifocal or multicentric breast cancer the largest lesion (target lesion) should be measured.
• HER2+ disease with confirmed ER-status, PR-status, HER2-status, PIK3CA mutation (tumor), Ki-67 value on core biopsy (target lesion). HER2-positive is defined according to current ASCO/CAP Guidelines. PIK3CA needs to be tested at the local site.
• Age ≥ 18 years, female and male.
• ECOG Performance status 0-1.
• Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results for LVEF must be above 55%.
• Laboratory requirements:
• Hematology
• Absolute neutrophil count (ANC) ≥ 1.5/ nL
• Platelets ≥ 100/ nL and
• Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L) Hepatic function

You may not qualify if:

• Patients will be ineligible for study participation if they comply with the following criteria:
• Patients with HER2-negative breast cancer.
• Inflammatory breast cancer.
• Patients with definitive clinical or radiologic evidence of Stage IV cancer or bilateral breast cancer or invasive breast cancer.
• Excisional biopsy or lumpectomy and/or axillary lymph node dissection and/or sentinel lymph node biopsy performed prior to study entry (biopsy of clinical involved LN is warranted).
• Prior chemotherapy or endocrine therapy or radiation therapy prior to study entry with the following exceptions:
• If medically indicated, initiation of hormonal replacement therapy (HRT) up to 28 days prior to randomization and use of established fertility preservation methods (including Gn) in young patients interested in subsequent pregnancies is allowed.
• Patients with a history of any treated malignancy and/or ongoing oncological treatment are ineligible, excluding cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. This also applies to patients who are at high risk that oncological treatment is indicated during study therapy.
• Known hypersensitivity reaction to one of the compounds or substances, and/or murine proteins, and/or recombinant human hyaluronidase used in this protocol.
• Type II diabetes requiring ongoing systemic treatment at the time of study entry or any history of Type 1 diabetes.
• Patients who are known HIV infection if any of the following apply: The CD4+ count is less than 350 cells/uL or there has been an opportunistic infection within the 12 months prior to the start of study treatment. Patients who are known to have HIV infection receiving immunosuppressive therapies and there is a potential DDI with any of the study treatments.
• Clinically significant and active liver disease, for example, sclerosing cholangitis, active viral hepatitis B or C infection, or autoimmune hepatic disorders.
• Patients with inflammatory bowel disease, such as Crohn's disease or ulcerative colitis, and active bowel inflammation (e.g., diverticulitis).
• Patients with any concurrent ocular or intraocular condition, excluding baseline cataracts, require medical or surgical intervention during the study period to prevent or treat vision loss. In addition, patients with active uveitis or vitritis, history of uveitis, or active infectious process in the eye.
• Patients with Previously or currently documented pneumonitis/interstitial lung disease, except if the investigator determines that it is non-active and does not require corticosteroid treatment.

Sponsors & Collaborators

• Zhimin Shao: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; 130-nm albumin-bound paclitaxel; inavolisib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Professor

Study Record Dates

• First Submitted: September 30, 2025
• First Posted: November 24, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): February 23, 2027
• Last Updated: November 24, 2025

Record last verified: 2025-11