A Study Evaluating the Efficacy and Safety of Inavolisib Plus FulvestrantVersus Alpelisib Plus Fulvestrant in Patients with Hormone ReceptorPositive, HER2-Negative, PIK3CA Mutated, Locally Advanced or MetastaticBreast Cancer who Progressed during or after CDK4/6 Inhibitor andEndocrine Combination Therapy

Phase 1

Recruiting

• Conditions: Metastatic breast cancer; MedDRA version: 23.0Level: PTClassification code: 10083232Term: HER2 negative breast cancer Class: 100000004864; MedDRA version: 20.1Level: PTClassification code: 10055113Term: Breast cancer metastatic Class: 100000004864; MedDRA version: 23.0Level: PTClassification code: 10083234Term: Hormone receptor positive breast cancer Class: 100000004864; MedDRA version: 20.0Level: PTClassification code: 10006187Term: Breast cancer Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2022-502322-41-00
• Lead Sponsor: F. Hoffmann-La Roche AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-03-03
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 458

Inclusion Criteria

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, Documented HR +/ HER2- tumor according to ASCO/CAP guidelines, Confirmation of biomarker eligibility: detection of specified mutation(s) of PIK3CA via specified test, Disease progression after or during treatment with a combination of cyclin dependent kinase 4/6i (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, Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2

Exclusion Criteria

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, Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes, 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 OR active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye, History of or active inflammatory bowel disease OR any active bowel inflammation, History of severe cutaneous reactions like Stevens-Johnson Syndrome, Erythema Multiforme, Toxic Epidermal Necrolysis, or Drug Reaction with Eosinphilia and Systemic Symptoms, Active ongoing osteonecrosis of the jaw

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of inavolisib plus fulvestrant compared with alpelisib plus<br>fulvestrant on the basis of blinded independent central review (BICR)-assessed<br>progression free survival (PFS);Secondary Objective: To evaluate the efficacy of inavolisib plus fulvestrant compared with alpelisib plus fulvestrant on the basis of overall survival (OS); BICR-assessed objective response rate (ORR), best overall response (BOR), clinical benefit rate; (CBR), and duration of response (DOR); and times to deterioration in pain, physical function, role function, and global health status (GHS)/health-related quality of life (HRQoL), To evaluate the safety and tolerability of inavolisib plus fulvestrant compared with alpelisib plus fulvestrant, To characterize the pharmacokinetics of inavolisib in the inavolisib + fulvestrant arm;Primary end point(s): BICR-assessed PFS

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Overall survival OS;Secondary end point(s):BICR-assessed Overall Response Rate;Secondary end point(s):BICR-assessed Best Overall Response;Secondary end point(s):BICR-assessed Clinical benefit rate;Secondary end point(s):BICR-assessed Duration of Response;Secondary end point(s):. Time to confirmed a deterioration (TTCD) in pain;Secondary end point(s):TTCD in physical functioning;Secondary end point(s):TTCD in role functioning;Secondary end point(s):TTCD in global health status/QOL;Secondary end point(s):Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) grading scale; treatment discontinuations due to adverse events;Secondary end point(s):Change from baseline in targeted clinical laboratory test results;Secondary end point(s):Plasma concentration of inavolisib at specified timepoints