Howell Township

Researchers are investigating multiple treatment combinations in participants with inoperable, locally advanced, or metastatic breast cancer. This Phase IbII, open-label, multicenter, randomized umbrella study focuses on three cohorts of estrogen receptor-positive ER breast cancer patients, including HER2-negative and HER2-positive subtypes, who have shown disease progression after prior therapies like CDK46 inhibitors or anti-HER2 treatments. The study is designed to adapt by adding or closing treatment arms based on clinical activity and safety. Participants receive different drug combinations depending on their cohort and treatment arm. Treatments include oral medications such as giredestrant, abemaciclib, ipatasertib, inavolisib, ribociclib, everolimus, samuraciclib, and palbociclib, as well as subcutaneous and intravenous therapies like pertuzumab and trastuzumab fixed-dose combination PH FDC SC and atezolizumab. Dosing schedules vary, with cycles lasting 21 or 28 days, continuing until unacceptable toxicity or disease progression. Some arms include combinations of these drugs tailored to specific tumor characteristics, such as PIK3CA mutations or estrogen receptor mutations. Throughout the study, participants undergo regular assessments including tumor measurements by RECIST v1.1 criteria to evaluate response, monitoring for adverse events, and cardiac function tests. Researchers track outcomes such as objective response, progression-free survival, disease control, clinical benefit rate, overall survival, and duration of response for up to six years. Safety is monitored up to 30 days after the last dose. Tumor specimens and blood samples are collected for biomarker evaluation. The study aims to gather comprehensive data on the efficacy and safety of these treatment combinations over an extended period.

Researchers are evaluating the effectiveness and safety of multiple treatment combinations in people with metastatic or locally advanced breast cancer. This umbrella study includes several groups based on specific breast cancer types and prior treatments, such as triple-negative breast cancer with PD-L1 positivity and hormone receptor-positive, HER2-negative or HER2-low disease with PIK3CA mutations. The study is divided into two stages, with the second stage allowing certain participants to continue treatment if their disease progresses or side effects occur. Participants receive different combinations of drugs depending on their group. Treatments include various chemotherapy drugs, immunotherapies like atezolizumab, targeted therapies such as inavolisib, and other agents given orally or intravenously in cycles lasting 21 or 28 days. Some participants may switch to alternative treatment combinations during the second stage if their disease worsens or they experience side effects while meeting eligibility criteria. Throughout the study, participants undergo regular assessments including imaging to measure tumor size according to RECIST v1.1 criteria and laboratory tests to monitor health and side effects. The main outcome measured is the objective response rate from baseline until disease progression or loss of clinical benefit, which may be observed for up to approximately 12 years. Secondary outcomes include progression-free survival, disease control rate, overall survival, duration of response, and the frequency of adverse events. Treatment continues until unacceptable toxicity or disease progression occurs.