A Randomized, Pilot Study to Evaluate the Molecular and Cellular Response to Treatment With Nivolumab With Either Adjuvant Ipilimumab or Relatlimab in Adult Patients With Surgically Resectable Melanoma Brain Metastases
概览
- 阶段
- 早期 1 期
- 干预措施
- Nivolumab
- 疾病 / 适应症
- Metastatic Melanoma
- 发起方
- H. Lee Moffitt Cancer Center and Research Institute
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Feasibility: Ability to recruit per treatment arm
- 状态
- 已完成
- 最后更新
- 26天前
概览
简要总结
The purpose of this pilot study is to determine the safety and feasibility of giving a single dose of Nivolumab with Ipilimumab or Relatlimab in participants with brain metastases from melanoma who can undergo surgery for removal of their brain metastases 7- 10 days after receiving the study drug.
研究者
入排标准
入选标准
- •Age 18 years old or older on day of signing the informed consent.
- •Histological confirmation of systemic cancer from melanoma.
- •Surgery for metastatic brain lesions (i.e., MBM) is needed but not imminent. Imminent defined as requiring emergent intervention. A multidisciplinary team will determine the appropriateness for resection via craniotomy and level of urgency for surgery of the MBM.
- •Resectable metastatic brain lesions (i.e., MBM) in whom surgical resection is a reasonable therapeutic option. A resectable metastatic brain lesion is defined as a lesion that is ≥10 mm in size of longest diameter and in a location outside of the brainstem. (Other target lesions, i.e. those that are not resected but are followed for response, can be ≥5 mm). A multidisciplinary team will determine the appropriateness for resection via craniotomy and level of urgency for surgery of the MBM.
- •Patient is on ≤4 mg/day dexamethasone or equivalent/day over pre-op period.
- •Patients treated with prior monotherapy with PD-1/PD-L1 are permitted.
- •Treatment with BRAF MEK inhibitors (BRAF MEKi) (for example, dabrafenib / trametinib) is permitted as long as has been at least five half-lives or one week prior to study treatment, whichever is shorter.
- •MRI with enhancing metastatic brain lesions (i.e., MBM) amenable to resection of contrast-enhancing tumor (determined by neurosurgeon). A multidisciplinary team will determine the appropriateness for resection via craniotomy and level of urgency for surgery of the MBM.
- •Patient willing to undergo craniotomy and resection.
- •Patient eligible for surgery in the 7-10 days after initial treatment.
排除标准
- •Has a metastatic brain lesion (or all brain lesions) that is (are) unresectable. Unresectable defined as located in the brainstem or measuring \<10 mm in longest diameter. Note, patients with multiple metastatic brain lesions that include non-targetable lesions of \<10 mm are allowed to enroll in the study as long as they have at least 1 lesion that is ≥10 mm in size of longest diameter.
- •Has clear evidence of leptomeningeal disease.
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment or five half-lives, whichever is shorter, or has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to a previously administered agent.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Physiologic doses of steroid therapy (≤ 3 mg/day dexamethasone equivalents) by the time of first dose of treatment are allowed.
- •Has a known history of active Bacillus Tuberculosis.
- •Hypersensitivity to either Nivolumab, Ipilimumab, or Relatlimab or any of its excipients.
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to a previously administered agent. Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- •Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with the use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
- •Has a prior history of life-threatening toxicity related to prior immune therapy (i.e., anti-CTLA-4 or anti- PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (i.e., hormone replacement after adrenal crisis).
研究组 & 干预措施
Pre-Surgery Nivolumab + Ipilimumab
Patients will be given one dose of Nivolumab (1mg/kg IV) and Ipilimumab (3mg/kg IV) prior to standard of care surgery for tumor resection.
干预措施: Nivolumab
Pre-Surgery Nivolumab + Ipilimumab
Patients will be given one dose of Nivolumab (1mg/kg IV) and Ipilimumab (3mg/kg IV) prior to standard of care surgery for tumor resection.
干预措施: Standard of Care Craniotomy
Pre-Surgery Nivolumab + Relatlimab(Opdualag)
Patients will be given one dose of Opdualag (Nivolumab 480 mg IV + Relatlimab160 mg IV), prior to standard of care surgery for tumor resection.
干预措施: Nivolumab + Relatlimab
Pre-Surgery Nivolumab + Relatlimab(Opdualag)
Patients will be given one dose of Opdualag (Nivolumab 480 mg IV + Relatlimab160 mg IV), prior to standard of care surgery for tumor resection.
干预措施: Standard of Care Craniotomy
Pre-Surgery Nivolumab + Ipilimumab
Patients will be given one dose of Nivolumab (1mg/kg IV) and Ipilimumab (3mg/kg IV) prior to standard of care surgery for tumor resection.
干预措施: Ipilimumab
结局指标
主要结局
Feasibility: Ability to recruit per treatment arm
时间窗: At 30 months
Feasibility is defined as being able to recruit 8 patients per treatment arm (16 total) within 30 months.
Comparison of immune cell population per treatment arm
时间窗: Up to 15 months
Investigators will compare immune cell population between treatment arms (Nivolumab + Ipilimumab vs Nivolumab +Relatlimab). The expression of PD-1 and PD-L1 in all samples collected will be evaluated, as well as the expression of cytokines and inflammatory cells including CD4+ T cells, CD8+ T cells, NK cells, T regulatory cells, B cells, plasma cells, IL-2, IFN-γ, TNF-β, GM-CSF, IL-3, IL-4, IL-5, IL-10, IL-13, myeloid-derived suppressor cells(MDSCs), dendritic cells (DCs), and macrophages. Size of immune cell population will be summarized in the following two ways. One is normalized per 100 cells so that the numbers are comparable between samples. The other estimation is the proportion of cells for each cell population. Other characterizations will be performed.