Endocrine-sensitive phosphatidylinositol 3-kinase (PIK3CA)-mutated, hormone receptor-positive, human epidermal growth factor receptor 2- (HER2-) negative advanced breast cancer Cancer
Conditions
Interventions
Experimental Arm: Inavolisib + Letrozole + CDK4/6i
Treatment Summary: Participants will receive oral inavolisib once daily (QD), oral letrozole QD, and oral palbociclib on Days 1-21 of each 28-day cy
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. De-novo hormone receptor-positive (HR +) , HER2- advanced breast cancer (ABC), or, alternatively, relapsed HR + , HER2- ABC after at least 2 years of standard neoadjuvant/adjuvant endocrine therapy – If a CDK4/6i was included as part of that treatment, progression must not have occurred during or within 1 year of receipt of the CDK4/6i. 2. Confirmation of biomarker eligibility: valid results from either central testing of blood or pre-existing local testing of blood or tumor tissue documenting the presence of a study-eligible PIK3CA mutation. 3. Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). 4. Men or women of postmenopausal or premenopausal/perimenopausal status. 5. For men (and women of pre-/peri-menopausal status: willingness to undergo and maintain treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy for the duration of study treatment. 6. Adequate hematologic and organ function within 14 days prior to initiation of study treatment.
Exclusion criteria
Exclusion criteria: 1. Any prior systemic therapy for locally advanced unresectable or metastatic breast cancer. 2. Appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines (e.g., patients with visceral crisis). 3. Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes. 4. Inability or unwillingness to swallow pills. 5. Known and untreated, or active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). 6. History of malignancy within 5 years prior to consent, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall Survival (OS) is measured using death records from any cause at randomization and up to 7 years 2. Investigator-assessed Objective Response Rate (ORR) is measured at baseline and up to 7 years 3. Investigator-assessed Duration of Response (DOR) is measured from the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first, up to 7 years 4. Investigator-assessed Clinical Benefit Rate (CBR) is measured at baseline and up to 7 years 5. Time to Confirmed Deterioration (TTCD) in Pain is measured from baseline until end of follow-up, up to 7 years 6. TTCD in Physical Function is measured from baseline until end of follow-up, up to 7 years 7. TTCD in Role Function is measured from baseline until end of follow-up, up to 7 years 8. TTCD in Global Health Status is measured from baseline until end of follow-up, up to 7 years 9. Percentage of Participants with Adverse Events is measured from baseline until end of follow-up, up to 7 years 10. Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities is measured using NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) at baseline and up to 7 years 11. Number of Participants Reporting Each Response Option for Treatment Side-effect Bother is measured using Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General Questionnaire (FACT-G) at baseline and up to 7 years 12. Change from Baseline in Symptomatic Treatment Toxicities is measured using the PRO-CTCAE at baseline and up to 7 years 13. Change from Baseline in Treatment Side-effect Bother is measured using the FACT-G GP5 Item at baseline and up to 7 years | — |
Countries
Argentina, Australia, Brazil, Canada, China, England, France, Germany, Italy, Mexico, Poland, South Africa, Spain, Switzerland, Taiwan, United Kingdom
Outcome results
None listed