A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy
- Conditions
- Breast Cancer
- Registration Number
- NCT05646862
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 400
Inclusion Criteria:<br><br> - If pre/perimenopausal women and men treatment with luteinizing hormone-releasing<br> hormone (LHRH) agonist therapy beginning at least 2 weeks prior to Day 1 of Cycle 1<br><br> - Histologically or cytologically confirmed adenocarcinoma of the breast that is<br> locally advanced or metastatic and is not amenable to surgical or radiation therapy<br> with curative intent<br><br> - Documented HR +/ HER2- tumor according to American Society of Clinical<br> Oncology/College of American Pathologists (ASCO/CAP) guidelines<br><br> - Confirmation of biomarker eligibility: detection of specified mutation(s) of PIK3CA<br> via specified test<br><br> - Disease progression after or during treatment with a combination of CDK4/6i and<br> endocrine therapy: <= 2 prior lines of systemic therapy in mBC setting; CDK4/6i<br> based therapy does not need to be the last one received prior study entry; one line<br> of chemotherapy in mBC setting allowed<br><br> - Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors<br> version 1.1 (RECIST v1.1)<br><br> - Participants for whom endocrine-based therapy is recommended and treatment with<br> cytotoxic chemotherapy is not indicated at time of entry into the study, as per<br> national or local treatment guidelines<br><br> - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2<br><br> - Life expectancy of > 6 months<br><br> - Adequate hematologic and organ function prior to initiation of study treatment<br><br>Exclusion Criteria:<br><br> - Metaplastic breast cancer<br><br> - Prior treatment in locally advanced or metastatic setting with any PI3K, AKT, or<br> mTOR inhibitor or any agent whose mechanism of action is to inhibit the<br> PI3K/-AKT/-mTOR pathway<br><br> - Participant who relapsed with documented evidence of progression > 12 months from<br> completion of adjuvant CDK4/6i based therapy with no treatment for metastatic<br> disease<br><br> - Pregnant, lactating, or breastfeeding, or intending to become pregnant during the<br> study or at least 60 days after the final dose of study treatment<br><br> - Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or<br> any history of Type 1 diabetes<br><br> - Inability or unwillingness to swallow pills<br><br> - Malabsorption syndrome or other condition that would interfere with enteral<br> absorption<br><br> - Any history of leptomeningeal disease or carcinomatous meningitis<br><br> - Known and untreated, or active central nervous system (CNS) metastases. Participants<br> with a history of treated CNS metastases are eligible if they meet specific certain<br> criteria<br><br> - Known active, systemic infection at study enrollment, or any major episode of<br> infection requiring treatment with intravenous antibiotics or hospitalization within<br> 7 days prior to Day 1 of Cycle 1<br><br> - Any concurrent ocular or intraocular condition that, in the opinion of the<br> investigator, would require medical or surgical intervention during the study period<br> to prevent or treat vision loss that might result from that condition<br><br> - Active inflammatory or infectious conditions in either eye or history of idiopathic<br> or autoimmune-associated uveitis in either eye<br><br> - Requirement for daily supplemental oxygen<br><br> - Symptomatic active lung disease, including pneumonitis<br><br> - History of or active inflammatory bowel disease<br><br> - Any active bowel inflammation<br><br> - Clinically significant and active liver disease, including severe liver impairment,<br> viral or other hepatitis, current alcohol abuse, or cirrhosis<br><br> - Participants with known human immunodeficiency virus infection that meet specific<br> criteria<br><br> - Investigational drug(s) within 4 weeks before randomization or within 5 half-lives<br> of the investigational drug(s), whichever is longer<br><br> - History of other malignancy within 5 years prior to screening, except for cancers<br> with very low risk of recurrence<br><br> - Chronic therapy of >= 10 mg of prednisone per day or an equivalent dose of other<br> anti-inflammatory corticosteroids or immunosuppressants for a chronic disease<br><br> - Allergy or hypersensitivity to components or excipients of the inavolisib,<br> fulvestrant, or alpelisib formulations<br><br> - History of severe cutaneous reactions like Stevens-Johnson Syndrome, Erythema<br> Multiforme, Toxic Epidermal Necrolysis, or Drug Reaction with Eosinphilia and<br> Systemic Symptoms<br><br> - Active ongoing osteonecrosis of the jaw
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS)
- Secondary Outcome Measures
Name Time Method Overall survival (OS);BICR-Assessed Overall Response Rate (ORR);BICR-Assessed Best Overall Response (BOR);BICR-Assessed Clinical Benefit Rate (CBR);BICR-Assessed Duration of Response (DOR);Time to Confirmed Deterioration (TTCD) in Pain;TTCD in Physical Functioning;TTCD in Role Functioning;TTCD in Global Health Status/Quality of Life (QOL);Percentage of Participants with Adverse Events;Plasma Concentration of Inavolisib at Specified Timepoints