NIMBUS: A Phase II Study of Nivolumab Plus Ipilimumab in Metastatic Hypermutated HER2-negative Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Ipilimumab
- Conditions
- Breast Cancer
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 30
- Locations
- 3
- Primary Endpoint
- Overall Response Rate of Nivolumab in Combination With Ipilimumab
- Status
- Active, not recruiting
- Last Updated
- 4 days ago
Overview
Brief Summary
This research study is studying a drug combination of nivolumab and ipilimumab as a possible treatment for hypermutated HER2 negative breast cancer.
The drugs involved in this study are:
- Nivolumab (Opdivo ®)
- Ipilimumab (Yervoy ®)
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. Nivolumab is called an anti- PD-1 or a checkpoint inhibitor and is an antibody (a type of human protein) designed to allow the body's own immune system to destroy tumors. Ipilimumab is called an anti-CTLA-4 and is a type of antibody that works to prevent your body's immune system from stopping to fight this specific cancer. The U.S. Food and Drug Administration (FDA) has not approved nivolumab for this specific disease but it has been approved for other uses including but not limited to non-small cell lung cancer, melanoma and renal cell carcinoma. The U.S. Food and Drug Administration (FDA) has not approved ipilimumab for this specific disease but it has been approved for other uses such as melanoma and renal cell carcinoma. The combination of nivolumab with ipilimumab may or may not increase anti-cancer activity by further boosting the immune system. At this time, the FDA has not approved nivolumab in combination with ipilimumab for this specific disease although these drugs have been approved for other uses such as melanoma and renal cell carcinoma. The purpose of this research study is to determine how nivolumab together with ipilimumab, works in treating breast cancer that has spread to other parts of the body. The investigators are also investigating whether there are certain DNA or protein markers in the blood or tumor tissue that may indicate whether the combination will work in future patients
Investigators
Sara Tolaney, MD
Primary Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •Participants must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
- •Breast cancer must be HER2-negative by IHC or non-amplified as determined by the current ASCO-CAP criteria. If patient has more than one histological result, the most recent one will be usedfor inclusion. Participants may be ER/PR positive or negative.
- •Patients must harbor tumors with total mutational burden (TMB) of at least 9 mutations per megabase assessed by a cancer-gene panel containing more than 300 genes, and performed in a CLIA verified laboratory. Tests like Foundation One, Oncopanel (DFCI), or IMPACT (MSKCC) are acceptable for including patients on this trial.
- •Participants must have measurable disease by RECIST version 1.
- •Participants must agree to undergo a research biopsy, if tumor is safely accessible, at baseline and at day 29 cycle 1 (+14 scheduling window). Previously collected archival tissue will be obtained on all participants. Participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or participant safety concern) may submit an archived specimen (block or if not possible, 20 unstained slides).
- •Prior chemotherapy: Participants may have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer and must have been off treatment with chemotherapy for at least 14 days prior to study treatment initiation.
- •Patients with hormone receptor positive breast cancer must have progressed on at least one prior line of endocrine therapy in the metastatic setting or have disease recurrence while on adjuvant endocrine therapy.
- •Participants should also be adequately recovered from acute toxicities of prior treatment, with the exception of alopecia and peripheral sensory neuropathy.
- •Prior biologic therapy: Patients must have discontinued all biologic therapy at least 14 days prior to study treatment initiation.
- •Prior radiation therapy: Patients may have received prior radiation therapy in either the metastatic or early-stage setting. Radiation therapy must be completed 14 days prior to study treatment initiation.
Exclusion Criteria
- •Major surgery within 2 weeks before the first dose of study treatment.
- •Concurrent administration of other anti-cancer therapy within 14 days of starting protocol therapy and during the course of this study.
- •The participant has received another investigational agent within 14 days of the first dose of study drug.
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody.
- •Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with a history of treated central nervous system (CNS) metastases are eligible. Treated brain metastases are defined as those having no evidence of progression for ≥ 2 weeks after treatment, and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging or CT scan) completed during screening. Subject must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily (or equivalent) for at least 7 days prior to first study treatment. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician. Participants with CNS metastases treated by neurosurgical resection or brain biopsy performed within 28 days before study treatment initiation will be excluded.
- •The subject has uncontrolled, significant intercurrent or recent illness. Individuals with a history of different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the investigator to be at low risk for recurrence of that malignancy.
- •Participant has an active infection requiring IV antibiotics at initiation of study therapy.
- •Patient has a medical condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, participants with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Subjects with current pneumonitis, or requiring supplementary O2 therapy.
- •The participant is known to be positive for human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. HIV-positive participants on combination antiretroviral therapy are ineligible
Arms & Interventions
Nivolumab+Ipilimumab
* Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks
Intervention: Ipilimumab
Nivolumab+Ipilimumab
* Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks
Intervention: Nivolumab
Outcomes
Primary Outcomes
Overall Response Rate of Nivolumab in Combination With Ipilimumab
Time Frame: 2 years
Overall Response Rate (ORR) is defined as the proportion of patients with complete or partial response evaluated by RECIST 1.1. Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcomes
- Overall Response Rate of the Combination According to Immune-related Response Criteria(2 years)
- Clinical Benefit Rate(2 Years)
- Progression Free Survival(2 years)
- Overall Survival(Participants were followed long-term for survival every 12 weeks from the end of treatment until death or lost to follow-up. Median follow-up in this study cohort was 9.7 months.)