An Open-Label, Dose-Finding and Proof of Concept Study of the PD-L1 Probody® Therapeutic , CX-072, as Monotherapy and in Combination With Yervoy (Ipilimumab) or With Zelboraf (Vemurafenib) in Subjects With Advanced or Recurrent Solid Tumors or Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 196
- 试验地点
- 3
- 主要终点
- The Number of Subjects Experiencing a Dose Limiting Toxicity (DLT) at Various Dose Levels When Given Multiple Doses of CX-072 as a Monotherapy or in Combination With Ipilimumab or Vemurafenib
研究概览
简要总结
The purpose of this first-in-human study of CX-072 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of CX-072 administered intravenously (IV) as a single agent or in combination with ipilimumab or vemurafenib in adult subjects with advanced or recurrent solid tumors or lymphomas. PROCLAIM-CX-072: PRObody CLinical Assessment In Man CX-072 clinical trial
CX-072 is a Probody® therapeutic directed against PD-L1 (programmed cell death ligand 1). Probody therapeutics are proteolytically-activatable antibodies (Abs) designed to widen the therapeutic index by minimizing drug interaction with normal tissue while retaining anti-tumor activity. Probody therapeutics are "masked" to attenuate binding to target in healthy tissue but can become "unmasked" in the tumor microenvironment by tumor-specific protease activity.
PROBODY is a U.S. registered trademark of CytomX Therapeutics, Inc.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Histologically confirmed diagnosis of metastatic or advanced unresectable tumors that progressed on standard therapy
- •Agreement to provide mandatory archival tissue or fresh biopsy.
- •At least 18 years of age.
排除标准
- •Prior therapy with a chimeric antigen receptor (CAR) T-cell containing regimen.
- •History of severe allergic or anaphylactic reactions to human monoclonal antibody therapy or known hypersensitivity to any Probody therapeutic.
- •Active or history of uveal, mucosal, or ocular melanoma. Human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness, chronic hepatitis B or C.
- •History of or current active autoimmune diseases, including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies, or type 1 insulin dependent diabetes mellitus.
- •History of syndrome or medical condition(s) that requires systemic steroids (> 10 mg daily prednisone equivalents) or immunosuppressive medications.
- •History of allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant.
- •Chemotherapy, biochemotherapy, radiation or immunotherapy or any investigational treatment within 30 days prior to receiving any study drug.
- •Major surgery (requiring general anesthesia) within 3 months or minor surgery (excluding biopsies conducted with local/topical anesthesia) or gamma knife treatment within 14 days (with adequate healing) of administration of any study drug.
研究组 & 干预措施
CX-072 expansion
Monotherapy CX-072 (Part D)
干预措施: CX-072 (Drug)
CX-072 long-term extension
Monotherapy CX-072
干预措施: CX-072 (Drug)
CX-072 #1
Monotherapy CX-072 (Part A)
干预措施: CX-072 (Drug)
CX-072 #2
Monotherapy CX-072 (Part A2)
干预措施: CX-072 (Drug)
CX-072 with Ipilimumab #1
Combination CX-072 + ipilimumab (Part B1)
干预措施: CX-072 (Drug)
CX-072 with Ipilimumab #1
Combination CX-072 + ipilimumab (Part B1)
干预措施: ipilimumab (Drug)
CX-072 with Ipilimumab #2
Combination CX-072 + ipilimumab (Part B2)
干预措施: CX-072 (Drug)
CX-072 with Ipilimumab #2
Combination CX-072 + ipilimumab (Part B2)
干预措施: ipilimumab (Drug)
CX-072 with Vemurafenib
Combination CX-072 + vemurafenib (Part C)
干预措施: CX-072 (Drug)
CX-072 with Vemurafenib
Combination CX-072 + vemurafenib (Part C)
干预措施: vemurafenib (Drug)
结局指标
主要结局
The Number of Subjects Experiencing a Dose Limiting Toxicity (DLT) at Various Dose Levels When Given Multiple Doses of CX-072 as a Monotherapy or in Combination With Ipilimumab or Vemurafenib
时间窗: 28 days (dose limiting toxicity period)
Adverse events (AEs) that were considered DLTs: * Grade 5 AEs * Grade 4 AEs judged by the Investigator to be treatment-related or judged by the Sponsor as a DLT, regardless of Investigator-attribution (with some exceptions) • Any Grade 4 endocrinopathy. * Grade 3 AEs judged by the Investigator to be treatment-related or by the Sponsor, regardless of Investigator-attribution (with some exceptions) • Any Grade 3 central nervous system event, regardless of duration or reversibility. * Grade 2 pneumonitis necessitating CX-072 discontinuation * Grade 2 ocular toxicity necessitating CX-072 discontinuation
次要结局
- The Percentage of Subjects Experiencing Anti-cancer Activity (ORR) When Given 10 mg/kg CX-072 as Monotherapy(2 years)