A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer

Roche

Status and phase: Enrolling; Phase 3

Conditions: Metastatic Breast Cancer

Treatments: Drug: Inavolisib; Drug: Optional Endocrine Therapy of Investigator's Choice; Drug: Taxane-based Chemotherapy; Drug: Phesgo; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05894239

2022-502046-28-00 (Registry Identifier)

WO44263

Details and patient eligibility

About

This study will evaluate the efficacy and safety of inavolisib in combination with Phesgo (pertuzumab, trastuzumab, and rHuPH20 injection for subcutaneous use) compared with placebo in combination with Phesgo, as maintenance therapy, after induction therapy in participants with previously untreated HER2-positive advanced breast cancer (ABC).

Enrollment: 230 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection
• Confirmation of HER2 biomarker eligibility based on valid results from central testing of tumor tissue documenting HER2-positivity
• Confirmation of PIK3CA-mutation biomarker eligibility based on valid results from central testing of tumor tissue documenting PIK3CA-mutated tumor status
• Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of >= 6 months
• LVEF (left ventricular ejection fraction) of at least 50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• Adequate hematologic and organ function prior to initiation of study treatment

Exclusion criteria

• Prior treatment in the locally advanced or metastatic setting with any PI3K, AKT, or mTOR inhibitor or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
• Any prior systemic non-hormonal anti-cancer therapy for locally advanced or metastatic HER2-positive breast cancer prior to initiation of induction therapy
• History or active inflammatory bowel disease
• Disease progression within 6 months of receiving any HER2-targeted therapy
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• Participants with active HBV infection
• Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis
• Symptomatic active lung disease, including pneumonitis or interstitial lung disease
• Any history of leptomeningeal disease or carcinomatous meningitis
• Serious infection requiring IV antibiotics within 7 days prior to Day 1 of Cycle 1
• Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition
• Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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230 participants in 3 patient groups

Induction Therapy: Phesgo plus Taxane-Based Chemotherapy

Other group

Description:

Participants will be administered the treatments as outlined in the interventions section.

Treatment:

Drug: Phesgo

Drug: Taxane-based Chemotherapy

Maintenance Therapy: Inavolisib plus Phesgo

Experimental group

Description:

Participants will be administered the treatments as outlined in the interventions section.

Treatment:

Drug: Phesgo

Drug: Optional Endocrine Therapy of Investigator's Choice

Drug: Inavolisib

Maintenance Therapy: Placebo plus Phesgo

Active Comparator group

Description:

Participants will be administered the treatments as outlined in the interventions section.

Treatment:

Drug: Placebo

Drug: Phesgo

Drug: Optional Endocrine Therapy of Investigator's Choice