The Purpose of This Study is to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo as Maintenance Therapy After First Line Induction Therapy in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Induction Therapy: Phesgo plus Taxane-Based Chemotherapy Participants will be administered the treatments as outlined in the interventions section. |
Drug: Phesgo
Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle.
Drug: Taxane-based Chemotherapy
During the induction therapy phase, the investigator's choice of taxane-based chemotherapy will be administered after Phesgo.
Other Names:
|
| Experimental: Maintenance Therapy: Inavolisib plus Phesgo Participants will be administered the treatments as outlined in the interventions section. |
Drug: Inavolisib
Participants will receive an inavolisib tablet to be taken orally (PO), once a day (QD), on Days 1-21 of each 21-day cycle, beginning on Day (D) 1 of Cycle (C) 1 of maintenance treatment.
Drug: Phesgo
Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle.
Drug: Optional Endocrine Therapy of Investigator's Choice
Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information.
Other Names:
|
| Active Comparator: Maintenance Therapy: Placebo plus Phesgo Participants will be administered the treatments as outlined in the interventions section. |
Drug: Phesgo
Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle.
Drug: Placebo
Inavolisib-matching tablet taken PO QD on Days 1-21 of each 21-day cycle, beginning on D1 C1 of maintenance treatment.
Drug: Optional Endocrine Therapy of Investigator's Choice
Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Investigator-Assessed Progression-Free Survival (PFS) [Up to approximately 40 months]
Secondary Outcome Measures
- Overall Survival (OS) [Up to approximately 111 months]
- Investigator-Assessed Objective Response Rate (ORR) [Up to approximately 111 months]
- Investigator-Assessed Duration of Response (DOR) [Up to approximately 111 months]
- Investigator-Assessed Clinical Benefit Rate (CBR) [Up to approximately 111 months]
- Investigator-Assessed PFS2 [Up to approximately 111 months]
- Mean and Mean Changes from Baseline Score in Function and Health-Related Quality of Life (HRQoL) [Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit every 6 months (up to 111 months). Each cycle is 21 days.]
Assessed through the use of the Functional (Role, Physical) and Global Health Status (GHS)/Quality of Life (QoL) scales of the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
- Percentage of Participants with Adverse Events [Day 1 until 30 days after the final dose of study treatment (up to approximately 111 months). Each cycle is 21 days.]
- Plasma Concentration of Inavolisib at Specified Timepoints [Day 1 of Cycles 1 and 4. Each cycle is 21 days.]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
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Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection
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Confirmation of HER2 biomarker eligibility based on valid results from central testing of tumor tissue documenting HER2-positivity
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Confirmation of PIK3CA-mutation biomarker eligibility based on valid results from central testing of tumor tissue documenting PIK3CA-mutated tumor status
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Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of >= 6 months
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LVEF (left ventricular ejection fraction) of at least 50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
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Adequate hematologic and organ function prior to initiation of study treatment
Exclusion Criteria:
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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
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Any prior systemic non-hormonal anti-cancer therapy for locally advanced or metastatic HER2-positive breast cancer prior to initiation of induction therapy
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History or active inflammatory bowel disease
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Disease progression within 6 months of receiving any HER2-targeted therapy
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Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
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Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis
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Symptomatic active lung disease, including pneumonitis or interstitial lung disease
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Any history of leptomeningeal disease or carcinomatous meningitis
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Serious infection requiring IV antibiotics within 7 days prior to Day 1 of Cycle 1
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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
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Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WO44263
- 2022-502046-28-00