Phase II Study of Sarilumab With Immune Checkpoint Inhibitor Rechallenge in Patients With Clinically Significant Immune Related Adverse Events (The IRIS Trial: Immune Checkpoint Inhibitor Rechallenge Involving Sarilumab)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Safety as assessed by Absence of any grade ≥2 Immune Related Adverse Event (irAE)
研究概览
简要总结
The study will enroll patients with history of malignancy treated with immune checkpoint inhibitors (ICI) that have developed a grade 2 or higher immune related adverse event requiring treatment discontinuation as deemed by the patient's treating physician. Patients will be sequentially enrolled into the single-arm study after meeting the pre-specified eligibility criteria
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible patients include patients with malignancy treated with ICI, who have been diagnosed with a clinically significant irAE (grade 1-3 attributed to ICI per CTCAE v6.0) requiring interruption of ICI by the treating physician. This study is limited to patients with the following specific irAEs as IL-6R blockade has demonstrated effectiveness in these conditions. Specific toxicities eligible for inclusion are; arthritis, colitis, PMR, nephritis, pneumonitis, hepatitis, myositis
- •The risk/benefit profile must favor ICI rechallenge as deemed per treating oncologist
- •The irAE must have improved to grade 1 by CTCAE criteria v6.0 for at least 1 week (exception for patients who have endocrinopathies which will typically require lifelong hormone supplementation)
- •Be willing and able to provide informed consent/assent for the trial
- •Be ≥18 years of age on the day of signing informed consent
- •Female subject of childbearing potential must have a negative urine or serum pregnancy test within 2 weeks prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Women of child-bearing potential (WOCBP):
- •Agree to use contraception while participating in this study, and for a period of 6 months following last dose of Sarilumab or ICI, as effects of these agents on the developing human fetus are unknown. Men whose partner is a WOCBP must also agree to use contraception during this period. Negative pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within two weeks of registration. Women must not be breastfeeding or plan to breastfeed for the duration of therapy or 6 months after.
- •Males must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 3 months after last dose of sarilumab, 120 days even if he has undergone a successful vasectomy
- •Have adequate organ function as described below
- •Absolute neutrophil count (ANC) ≥500/mm3
- •Platelets ≥ 50,000/mm3
- •AST/ALT <=3× institutional upper limit of normal
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Completed informed consent process, including signing Institutional Review Board (IRB)/Ethics Committee (EC)-approved informed consent form.
- •Willing and able to comply with clinical trial instructions and requirements. Subjects must be competent to report AEs, understand the drug dosing schedule, and use of medications to control AEs
排除标准
- •History of grade 4 irAE (attributed to ICI per CTCAE v6.0)
- •History of cardiovascular or neurologic immune related adverse event
- •Active or serious infections
- •History of latent Tuberculosis (TB) or uncontrolled hepatitis B/C
- •History of gastrointestinal perforation or diverticulitis
- •Severe hepatic impairment (AST, ALT >3xULN; total bilirubin >1.5xULN)
- •Significant hematological abnormalities
- •On prednisone equivalent >10mg prior to first dose of trial treatment
- •History of immunodeficiency disorder
- •Treatment with a non-biologic immunosuppressive or immune-modulating drug (e.g. methotrexate, azathioprine, mycophenolate, cyclosporine, hydroxychloroquine, penicillamine) at time of enrollment
- •Treatment with other immune-modulating biologic agents (e.g TNF-alpha inhibitors) within 8 weeks prior to enrollment
- •History of anaphylaxis or IgE-mediated hypersensitivity to sarilumab or history of allergic reactions attributed to compounds of similar chemical or biologic composition to sarilumab.
- •The subject must meet all of the inclusion criteria and none of the exclusion criteria.
- •No eligibility waivers will be granted.
研究组 & 干预措施
Sarilumab with ICI
Sarilumab is dosed 200 mg subcutaneously every two weeks for a total of 24 weeks. ICI will be dosed by investigator's choice per standard of care for malignancy. ICI will be administered on day 1 of each 3 or 4 week cycle depending on the selected ICI agent. Administration of ICI will continue past the 24 week timepoint per discretion of the investigator.
干预措施: ICI Therapy (Drug)
Sarilumab with ICI
Sarilumab is dosed 200 mg subcutaneously every two weeks for a total of 24 weeks. ICI will be dosed by investigator's choice per standard of care for malignancy. ICI will be administered on day 1 of each 3 or 4 week cycle depending on the selected ICI agent. Administration of ICI will continue past the 24 week timepoint per discretion of the investigator.
干预措施: Sarilumab (Drug)
结局指标
主要结局
Safety as assessed by Absence of any grade ≥2 Immune Related Adverse Event (irAE)
时间窗: From enrollment to the end of treatment at 53 weeks
Absence of any grade ≥2 Immune Related Adverse Event (irAE) in the 3 months after ICI rechallenge, defined as grade ≥2 adverse event attributed to ICI by CTCAE v6.0
次要结局
- Safety and tolerability as assessed by occurrence of adverse events(From enrollment to the end of treatment at 53 weeks)
- Absence of Serious immune-related adverse event(From enrollment to the end of treatment at 53 weeks)
- Efficacy as assessed by progression free survival(From enrollment to the end of treatment at 53 weeks)
- Efficacy as assessed by Overall survival(From enrollment to the end of treatment at 53 weeks)