A Phase 1/1b, First-In-Human, Multi-Part, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF6002 as a Monotherapy and in Combination With Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 170
- 试验地点
- 32
- 主要终点
- Number of participants with dose-limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, drug-levels, drug-effects and preliminary anti-tumor activity of DF6002 alone and in combination with Nivolumab in participants with advanced solid tumors.
详细描述
Assess the safety and tolerability of subcutaneous (SC) and intravenous (IV) administration of DF6002, as monotherapy and in combination with nivolumab, and to determine the maximum tolerated dose (MTD) and recommended efficacy expansion dose (REED) of SC and IV DF6002, both as monotherapy and in combination with nivolumab, for patients with advanced (unresectable, recurrent, or metastatic) solid tumors.
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
- •Advanced/metastatic solid tumors, for which no standard therapy exists or standard therapy has failed among the following tumor types: melanoma, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell, urothelial, gastric, esophageal, cervical, hepatocellular, merkel cell, cutaneous squamous cell carcinoma, renal cell, endometrial, triple-negative breast, ovarian, and prostate
- •ECOG performance status of 0 or 1
- •Clinical or radiological evidence of disease
- •Adequate hematological, hepatic and renal function
- •Anticoagulants are required for the following: Khorana Risk Score ≥ 2 or as assessed by Investigator as being at high risk for venous thromboembolism (VTE) or history of VTE ≥ 6 months from enrollment
排除标准
- •Concurrent anticancer treatment (with the exception of palliative bone directed radiotherapy), immune therapy, or cytokine therapy (except for erythropoietin), major surgery (excluding prior diagnostic biopsy), concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of study treatment
- •Prior treatment with DF6002, recombinant human interleukin-12 (rhIL-12)-directed therapy, or any drug containing an interleukin-12 (IL-12) moiety
- •Previous malignant disease other than the current target malignancy within the last 3 years, with the exception of basal or squamous cell carcinoma of the skin, localized prostate cancer or cervical carcinoma in situ
- •Rapidly progressive disease
- •Serious cardiac illness or medical conditions
- •Known diagnosis of antiphospholipid syndrome or clinically significant hereditary thrombophilia
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Dose Escalation / Monotherapy / Subcutaneously or Intravenously
Subcutaneous portion of the study is complete. Dosing DF6002 Q4W
干预措施: DF6002 (Drug)
Dose Escalation / Combination / Subcutaneously or Intravenously
Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W
干预措施: DF6002 (Drug)
Dose Escalation / Combination / Subcutaneously or Intravenously
Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W
干预措施: Nivolumab (Drug)
Safety/PK/PD / Monotherapy / Subcutaneously or Intravenously
Subcutaneous portion of the study is complete. Dosing DF6002 Q4W
干预措施: DF6002 (Drug)
Safety/PK/PD / Combination / Subcutaneously or Intravenously
Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W
干预措施: DF6002 (Drug)
Safety/PK/PD / Combination / Subcutaneously or Intravenously
Subcutaneous portion of the study is complete. Dosing DF6002 Q4W Dosing nivolumab Q4W
干预措施: Nivolumab (Drug)
Efficacy Expansion / Combination / Subcutaneously or Intravenously / Melanoma
Subcutaneous portion of the study is complete. 2L+ melanoma Dosing DF6002 Q4W Dosing nivolumab Q4W
干预措施: DF6002 (Drug)
Efficacy Expansion / Combination / Subcutaneously or Intravenously / Melanoma
Subcutaneous portion of the study is complete. 2L+ melanoma Dosing DF6002 Q4W Dosing nivolumab Q4W
干预措施: Nivolumab (Drug)
Efficacy Expansion / Combination / Subcutaneously or Intravenously / Non-Melanoma
Subcutaneous portion of the study is complete. 2L+ non-melanoma skin cancer (including cSCC, BCC, and MCC) Dosing DF6002 Q4W Dosing nivolumab Q4W
干预措施: DF6002 (Drug)
Efficacy Expansion / Combination / Subcutaneously or Intravenously / Non-Melanoma
Subcutaneous portion of the study is complete. 2L+ non-melanoma skin cancer (including cSCC, BCC, and MCC) Dosing DF6002 Q4W Dosing nivolumab Q4W
干预措施: Nivolumab (Drug)
结局指标
主要结局
Number of participants with dose-limiting toxicities (DLTs)
时间窗: During the first 3 weeks of treatment
Dose Escalation
Overall Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per an Independent Endpoint Review Committee (IERC)
时间窗: Up to 2 years
Efficacy Expansion Arms
次要结局
- Clinical benefit rate (CBR) according to RECIST 1.1 per Investigator assessment(Up to 2 years)
- Overall Survival (OS)(Up to 5 years)
- Amount of Treatment Emergent Adverse Events (TEAEs)(Up to 2 years)
- Severity of TEAEs(Up to 2 years)
- Duration of TEAEs(Up to 2 years)
- Number of participants with changes from baseline in clinical laboratory parameters(Up to 2 years)
- Number of participants with changes from baseline in electrocardiogram (ECG) parameters(Up to 2 years)
- Number of participants with changes from baseline in vital sign parameters(Up to 2 years)
- Duration of Response (DOR) according to RECIST 1.1 per Investigator assessment(Up to month 24)
- Area under the plasma concentration-time curve from the time of dosing to the time of the last observation (AUC 0-T)(Up to day 28)
- Area under the plasma concentration-time curve from the time of dosing extrapolated to infinity (AUC 0-INF)(Up to day 28)
- Maximum serum concentration observed post-dose (Cmax)(Up to day 28)
- Best overall response (BOR) according to RECIST 1.1 per Investigator assessment(Approximately one year)
- Confirmed ORR per RECIST 1.1 per Investigator assessment(Up to 2 years)
- Progression-free survival (PFS) according to RECIST 1.1 per Investigator assessment(Up to 2 years)
- CBR according to RECIST 1.1 per IERC(Up to 2 years)
- PFS according to RECIST 1.1 per IERC(Up to 2 years)
- DOR according to RECIST 1.1 per IERC(Up to month 24)
- Unconfirmed response after 4 cycles according to RECIST 1.1(Up to 2 years)
- Serum titers of anti-DF6002 antibodies(Up to 2 years)
- Serum titers of anti-nivolumab antibodies(Up to 2 years)