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+ Breas
Details
Status
Open: Currently recruiting participants.
Closed: Recruitment either has not started or has paused or completed.
Study Type
Interventional (clinical trials): Test treatments.
Observational: Conduct surveys and interviews, study medical records and otherwise observe people or groups over time.
Interventional
Study Phase
Each study phase tests different aspects of the medication or treatment:
- Phase I: safety and dosing
- Phase II: effectiveness and side effects
- Phase III: efficacy compared to standard treatments
- Phase IV: long-term safety after approval for use
I
Location(s)
Johns Hopkins study sites. Additional study locations may be found on ClinicalTrials.gov.
The Johns Hopkins Hospital
1800 Orleans St Baltimore, MD 21287
Keywords
Contact Us
(410) 955-8964Brief Summary
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: Fulvestrant Arm 2: Atezolizumab + Cobimetinib Arm 3: Atezolizumab + Fulvestrant Arm 4: Atezolizumab + Ipatasertib Arm 5: Atezolizumab + Ipatasertib + Fulvestrant Crossover Arm (Stage 2): Atezolizumab + Bevacizumab + Endocrine Therapy Expansion phase: Mandatory biopsy cohort: Atezolizumab+ +Cobimetinib +Fulvestrant + Ipatasertib
Study 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.
Eligibility
Inclusion Criteria for Both Stages:
- Measurable disease per RECIST v1.1
- Adequate hematologic and end organ function
- Disease progression during or after first- or second-line hormonal therapy with CDK4/6 inhibitor
Inclusion Criteria for Stage 1:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Metastatic or inoperable, locally advanced, histologically or cytologically confirmed invasive HR-positive HER2-negative breast cancer
- Recommended for endocrine therapy, and cytotoxic chemotherapy not indicated at study entry
- Recurrence or progression following most recent systemic breast cancer therapy
- Disease progression during or after first- or second-line hormonal therapy for locally advanced or metastatic disease
- Postmenopausal according to protocol-defined criteria
- Life expectancy >3 months
- Available tumor specimen for determination of PD-L1 status
Inclusion Criteria for Stage 2:
- ECOG performance status of 0-2
- Ability to initiate treatment within 3 months after disease progression or unacceptable toxicity on a Stage 1 regimen
Exclusion Criteria for Both Stages:
- Significant or uncontrolled comorbid disease as specified in the protocol
- Uncontrolled tumor-related pain
- Autoimmune disease except for stable/controlled hypothyroidism, Type 1 diabetes mellitus, or certain dermatologic conditions
- Positive human immunodeficiency virus test
- Active hepatitis B or C
- Active tuberculosis
- Severe infection within 4 weeks and/or antibiotics within 2 weeks prior to study treatment
- Prior allogeneic stem cell or solid organ transplantation
- History of malignancy other than breast cancer within 2 years prior to screening except those with negligible risk of metastasis/death
- History of or known hypersensitivity to study drug or excipients
- For patients entering Stage 2, recovery from all immunotherapy-related adverse events to Grade 1 or better or to baseline at the time of consent
Exclusion Criteria for Stage 1:
- Prior fulvestrant or cytotoxic chemotherapy for metastatic breast cancer, or certain other agents as specified in the protocol
- Unresolved AEs from prior anti-cancer therapy
- Eligibility only for the control arm
- Prior treatment with inhibitors as specified in the protocol
Exclusion Criteria for Stage 2:
- Unacceptable toxicity with atezolizumab during Stage 1
- Uncontrolled cardiovascular disease or coagulation disorder, including use of anticoagulants as specified in the protocol
- Significant abdominal or intestinal manifestations within 6 months prior to treatment
- Grade 2 or higher proteinuria