A Phase 1 Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 132
- 试验地点
- 11
- 主要终点
- Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0
研究概览
简要总结
This is a study to determine the maximum tolerated dose (MTD) for CDX-1140 (CD40 antibody), either alone or in combination with CDX-301 (FLT3L), pembrolizumab, or chemotherapy and to further evaluate its tolerability and efficacy in expansion cohorts once the MTD is determined.
详细描述
This study will determine the MTD of CDX-1140 while also evaluating the safety, tolerability and efficacy of CDX-1140 alone (Part 1) or in combination with CDX-301 (Part 2), pembrolizumab (Part 3), or chemotherapy (Part 4) in patients with cancer.
Eligible patients that enroll to the dose-escalation portion of the study will be assigned to one of several dose levels of CDX-1140. The dose-escalation part of the study will test the safety profile of CDX-1140, alone or in combination with CDX-301, pembrolizumab or chemotherapy and determine which dose(s) of CDX-1140 will be studied in the expansion portions of the study.
All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Recurrent, locally advanced or metastatic melanoma (including mucosal and/or ocular), bladder/urothelial, non-small cell lung cancer, pancreatic adenocarcinoma, breast, colorectal, gastric, esophageal, renal cell, hepatic, ovarian fallopian or primary peritoneal carcinoma, head and neck, and cholangiocarcinoma. Additional tumor types (except primary CNS tumors) may be enrolled after discussion with, and approval from, the medical monitor.
- •Must have received all standard of care therapies (approved or unapproved) as deemed appropriate by the treating physician. Patients who refuse standard therapy are excluded from the study.
- •If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 3 months following last treatment
- •Willingness to undergo a pre-treatment and on-treatment biopsy, if required.
- •Additional Inclusion Criteria for Part 1:
- •Advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, or indolent B-cell lymphoma are also eligible.
- •Lymphoma patients must have received ≥ 1 prior systemic therapy
- •Additional Inclusion Criteria for Part 3:
- •Patients must have documented progression while receiving anti-PD-1 or anti-PD-L1 based regimens for FDA approved indications
- •Patients cannot have received more than one anti-PD-1 or anti-PD-L1 based regimen
- •Additional Inclusion Criteria for Part 4:
- •Patients must have metastatic pancreatic adenocarcinoma, and have not received previous treatment in a metastatic setting
排除标准
- •History of severe hypersensitivity reactions to other monoclonal antibodies.
- •Previous treatment with any anti-CD40 antibody or with FLT3L.
- •Inadequate washout period from prior therapy as defined in the Protocol.
- •Major surgery within 4 weeks prior to study treatment.
- •Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to study treatment.
- •Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers. For all other cancers, the patient must be disease-free for at least 3 years to be allowed to enroll.
- •Active, untreated central nervous system metastases.
- •Active autoimmune disease or documented history of autoimmune disease.
- •History of (non-infectious) pneumonitis or has current pneumonitis.
- •Active infection requiring systemic therapy, known infection of HIV, Hepatitis B, or Hepatitis C.
- •Additional Exclusion Criteria for lymphoma patients in Part 1:
- •Prior allogenic stem cell transplantation
- •Patients who have received autologous stem cell transplant ≤ 12 weeks prior to the first dose of study drug.
- •There are additional criteria your study doctor will review with you to confirm your eligibility for the study.
研究组 & 干预措施
CDX-1140 and CDX-301
Part 2: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance or two years of treatment. A fixed dose of CDX-301 is injected once a day for five days before cycles 1 and 2 of CDX-1140.
干预措施: CDX-301 (Drug)
CDX-1140
Part 1: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance, or two years of treatment.
干预措施: CDX-1140 (Drug)
CDX-1140 and CDX-301
Part 2: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance or two years of treatment. A fixed dose of CDX-301 is injected once a day for five days before cycles 1 and 2 of CDX-1140.
干预措施: CDX-1140 (Drug)
CDX-1140 and pembrolizumab
Part 3: Eligible patients will receive CDX-1140, based on cohort assigned, in 3 week cycles until progression, or intolerance, or two years of treatment. A fixed dose of pembrolizumab will also be given in 3 week cycles.
干预措施: CDX-1140 (Drug)
CDX-1140 and pembrolizumab
Part 3: Eligible patients will receive CDX-1140, based on cohort assigned, in 3 week cycles until progression, or intolerance, or two years of treatment. A fixed dose of pembrolizumab will also be given in 3 week cycles.
干预措施: pembrolizumab (Drug)
CDX-1140 and chemotherapy
Part 4: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, or intolerance, or two years of treatment. Chemotherapy will also be given according to standard of care.
干预措施: CDX-1140 (Drug)
CDX-1140 and chemotherapy
Part 4: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, or intolerance, or two years of treatment. Chemotherapy will also be given according to standard of care.
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0
时间窗: From first dose through 30 days after last dose
The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.
次要结局
- Clinical benefit rate(Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years)
- Duration of Response(First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years))
- Progression-free survival(From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years))
- Objective Response Rate(Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years.)
- Overall survival(The time from start of study drug to death from any cause (up to approximately 1-3 years))
- Immunogenicity evaluation(Prior to each dose of study treatment and at treatment discontinuation, up to approximately 1-3 years)
- Pharmacokinetic evaluation(Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years)