Comparing 3 approaches for breast cancer

Inclusion

• +Allergy or hypersensitivity to components or excipients of the inavolisib, fulvestrant, or alpelisib formulations
• +Allergy or hypersensitivity to components or excipients of the inavolisib, fulvestrant formulations
• +Any history of leptomeningeal disease or carcinomatous meningitis
• +Known and untreated, or active central nervous system (CNS) metastases. Participants with a history of treated CNS metastases are eligible if they meet specific certain criteria
• +Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis
• +for Main Study and Sub-study:
• +If pre/perimenopausal women and men treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy beginning at least 2 weeks prior to Day 1 of Cycle 1
• +Documented HR +/ HER2- tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
• +Confirmation of biomarkerBiomarkerSomething measurable in the body used as a signal of what is happening.Read more → eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more →: detection of specified mutation(s) of PIK3CA via specified test
• +Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• +Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• +Life expectancy of \> 6 months
• +Adequate hematologic and organ function prior to initiation of study treatment
• +Exclusion CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → for both Main Study and Sub-study:
• +Metaplastic breast cancer
• +Prior treatment in 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
• +Participant who relapsed with documented evidence of progression \> 12 months from completion of adjuvant CDK4/6i based therapy with no treatment for metastatic disease
• +Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• +Inability or unwillingness to swallow pills
• +Malabsorption syndrome or other condition that would interfere with enteral absorption
• +Any concurrent ocular or intraocular condition that, in the opinion of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, 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
• +Requirement for daily supplemental oxygen
• +Symptomatic active lung disease, including pneumonitis
• +History of or active inflammatory bowel disease
• +Any active bowel inflammation
• +Participants with known human immunodeficiency virus infection that meet specific criteria
• +History of other malignancy within 5 years prior to screeningScreeningThe checks done before joining, to see whether a study fits.Read more →, except for cancers with very low risk of recurrence
• +Chronic therapy of \>= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
• +Active ongoing osteonecrosis of the jaw
• +Exclusion Criteria for Main Study Only:
• +Known active, systemic infection at study enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →, or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 7 days prior to Day 1 of Cycle 1
• +Investigational drug(s) within 4 weeks before randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more → or within 5 half-lives of the investigational drug(s), whichever is longer
• +History of severe cutaneous reactions like Stevens-Johnson Syndrome, Erythema Multiforme, Toxic Epidermal Necrolysis, or Drug Reaction with Eosinphilia and Systemic Symptoms
• +Exclusion Criteria for Sub-study Only:
• +Known active, systemic infection at study enrollment, or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 7 days prior to Day -4 of Cycle 1
• +Investigational drug(s) within 4 weeks prior to Day -4 or within 5 half-lives of the investigational drug(s), whichever is longer
• +Treatment with mild, moderate, or strong inducers of CYP2B6, CYP3A4, and/or CYP2C19 (including St. John's Wort) within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment on Day -4 until after the final PKPharmacokineticsThe study of how the body absorbs, distributes, and clears a treatment.Read more → sample has been collected on Day 15 of Cycle 1
• +Treatment with mild, moderate, or strong inhibitors of CYP2B6, CYP3A4, and/or CYP2C19 (including grapefruit juice or supplements) within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment on Day -4 until after the final PK sample has been collected on Day 15 of Cycle 1
• +Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or at least 60 days after the final dose of study treatment
• +Pregnant, lactating, or breastfeeding, or intending to become pregnant during the substudy or within 2 weeks after the final dose of inavolisib and within 2 years after the final dose of fulvestrant, whichever is longer
• +Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent
• +Disease progression after or during treatment with a combination of CDK4/6i and endocrine therapy: \<= 2 prior lines of systemic therapy in mBC setting; CDK4/6i based therapy does not need to be the last one received prior study entry; one line of chemotherapy in mBC setting allowed
• +Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines