J17107 - A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Hormone Receptor-Positive Her2-Negative Breast Cancer (Morpheus-HR+ Breast Cancer)
Johns Hopkins Kimmel Cancer Center in Baltimore
To Evaluate The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations
Patients with HR +, HER2 neg, MBC or LABC who have had progression on first line CDK 4/6 inhibitor.PS of 0-2 No prior Fulvestrant allowed. Post-menopausal (LHRH agonist allowed). RECIST measurable and biopsiable disease. No prior chemo for MBC. No prior PDL 1/PD1 allowed. No autoimmune. LVEF greater than 50. No retinal disorders. No insulin dependent diabetes. No malabsorption syndromes.
The study is being conducted in two stages. During Stage 1, patients will be randomized to fulvestrant or an Atezolizumab-containing doublet or triplet combination. Those who experience progression/toxicity may be eligible to receive a new triplet combination treatment in Stage 2. Patients will be randomized to the following treatment arms:Safety Run In- 6 patients: Ipatasertib + Atezolizumab (no randomization)Arm 1: FulvestrantArm 2: Atezolizumab + Cobimetinib Arm 3: Atezolizumab + FulvestrantArm 4: Atezolizumab + IpatasertibArm 5: Atezolizumab + Ipatasertib + FulvestrantCrossover Arm (Stage 2): Atezolizumab + Bevacizumab + Endocrine TherapyExpansion phase: Mandatory biopsy cohort: Atezolizumab+ +Cobimetinib +Fulvestrant + IpatasertibStudy requires: Archival tissue available, on treatment biopsies, Research blood samples, Ophthalmology exams, and echocardiograms. If on mandatory biopsy cohort requires up to 3-4 biopsies.
08/11/2020 05:02 AM