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

• ClinicalTrials.gov Identifier: NCT05894239
• Recruitment Status: Recruiting
• First Posted: June 8, 2023
• Last Update Posted: May 17, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: May 24, 2023
• First Posted Date: June 8, 2023
• Last Update Posted Date: May 17, 2024
• Actual Study Start Date: July 28, 2023
• Estimated Primary Completion Date: October 31, 2028 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 7, 2023): Investigator-Assessed Progression-Free Survival (PFS) [ Time Frame: Up to approximately 40 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 7, 2023)

• Overall Survival (OS) [ Time Frame: Up to approximately 111 months ]
• Investigator-Assessed Objective Response Rate (ORR) [ Time Frame: Up to approximately 111 months ]
• Investigator-Assessed Duration of Response (DOR) [ Time Frame: Up to approximately 111 months ]
• Investigator-Assessed Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 111 months ]
• Investigator-Assessed PFS2 [ Time Frame: Up to approximately 111 months ]
• Mean and Mean Changes from Baseline Score in Function and Health-Related Quality of Life (HRQoL) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 1 of Cycles 1 and 4. Each cycle is 21 days. ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Metastatic Breast Cancer

Intervention

• 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: Placebo
  Inavolisib-matching tablet taken PO QD on Days 1-21 of each 21-day cycle, beginning on D1 C1 of maintenance treatment.
• Drug: Taxane-based Chemotherapy
  During the induction therapy phase, the investigator's choice of taxane-based chemotherapy will be administered after Phesgo.
  Other Name: non-investigational medicinal product (NIMP)
• 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 Name: NIMP

Study Arms

• Induction Therapy: Phesgo plus Taxane-Based Chemotherapy
  Participants will be administered the treatments as outlined in the interventions section.
  Interventions:

  • Drug: Phesgo
  • Drug: Taxane-based Chemotherapy
• Experimental: Maintenance Therapy: Inavolisib plus Phesgo
  Participants will be administered the treatments as outlined in the interventions section.
  Interventions:

  • Drug: Inavolisib
  • Drug: Phesgo
  • Drug: Optional Endocrine Therapy of Investigator's Choice
• Active Comparator: Maintenance Therapy: Placebo plus Phesgo
  Participants will be administered the treatments as outlined in the interventions section.
  Interventions:

  • Drug: Phesgo
  • Drug: Placebo
  • Drug: Optional Endocrine Therapy of Investigator's Choice

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 7, 2023): 230
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 31, 2028
• Estimated Primary Completion Date: October 31, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: WO44263 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, China, Colombia, Finland, France, Germany, Hong Kong, India, Italy, Korea, Republic of, Mexico, Poland, Singapore, South Africa, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05894239
• Other Study ID Numbers: WO44263; 2022-502046-28-00 ( Registry Identifier: EU Clinical Trials )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2024