63723283LUC1001: A First-in-Human, Open-label, Phase 1/2 Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Subjects With Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 234
- 试验地点
- 20
- 主要终点
- Part 2: Overall Response Rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Subjects With Selected Advanced Solid Tumors
研究概览
简要总结
The Primary purpose of this study is to identify the recommended Phase 2 dose [RP2D(s)] for JNJ-63723283 in Part 1, to assess the anti-tumor activity of JNJ-63723283 at the RP2D(s) in participants with selected advanced cancers including non-small-cell lung cancer (NSCLC), melanoma, renal, bladder, small-cell lung cancer (SCLC), gastric/esophageal cancer, and high-level microsatellite instability (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC) in Part 2, to determine one or more additional RP2Ds in Parts 3 and 4.
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
- •Parts 1-4: Have an Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1
- •Parts 1-4: Has thyroid function laboratory values within normal range
- •Parts 1-4: Females of childbearing potential must have a negative serum pregnancy test
- •Parts 1-4: Willing and able to adhere to the prohibitions and restrictions specified in this protocol
- •For Part 2 only: Participants enrolled into Part 2 must have tumor tissue available for correlative studies. Fresh tumor biopsy is preferred. Archival tissue must meet the following criteria: archival sections within 4 months of sectioning that have been stored at 2 degree to 8 degree Celsius in the dark or archival tumor blocks within 5 years of collection. Participants without tissues meeting the aforementioned archived tissue criteria must undergo a fresh biopsy
- •Parts 1 to 4: Have evaluable disease
排除标准
- •Has uncontrolled intercurrent illness, including but not limited to ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure (New York Heart Association class III-IV), unstable angina pectoris, cardiac arrhythmia, poorly controlled hypertension or diabetes, or psychiatric illness/social situation that would limited compliance with study requirements
- •Has had prior treatment with an anti-Programmed-cell death receptor-1 (PD-1) antibody, anti-the ligand to programmed-cell death 1 (PD-L1) antibody or anti-the ligand to programmed-cell death 2 (PD-L2) antibody
- •Treatment with any local or systemic anti-neoplastic therapy, radiotherapy (excluding limited palliative radiation), or investigational anticancer agent within 14 days or 4 half lives, whichever is longer, up to a maximum wash-out period of 28 days prior to the initiation of study drug administration
- •Grade 3 or higher toxicity effects from previous treatment with immunotherapy
- •A female who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 5 months after the last dose of study drug
研究组 & 干预措施
JNJ-63723283
In Part 1, the first cohort will receive JNJ-63723283 at a starting dose of 80 milligram (mg), intravenous (IV) every 2 weeks. JNJ-63723283 doses will be escalated following a modified Continual Reassessment Method (mCRM). Multiple doses, dose administration routes (subcutaneous [SC] or IV), and dose schedules may be explored. In Part 2, participants will receive JNJ-63723283 at the recommended Phase 2 dose (RP2D) determined in Part 1. In Part 3, participants will receive JNJ-63723283 to evaluate pharmacokinetic (PK), pharmacodynamic (PD) and safety. In Part 4, participants will receive JNJ-63723283 at the dose level determined in Part 3. Additional cohorts may be enrolled in Part 4.
干预措施: JNJ-63723283 (Drug)
结局指标
主要结局
Part 2: Overall Response Rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Subjects With Selected Advanced Solid Tumors
时间窗: Up to 2 years 6 months
Objective Response Rate (ORR) is defined as percentage of subjects with best objective response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria.
Part 1: Frequency and Severity of Dose-Limiting Toxicity (DLT)
时间窗: Up to 2 years 6 months
Frequency and severity of dose-limiting toxicity will be reported.
Parts 3 and 4: Area Under the Serum Concentration Versus Time Curve from Time Zero to Dosing Interval (AUC [0-tau])
时间窗: Up to 2 years 6 months
AUC (0-tau) is defined as area under the serum concentration versus time curve from time zero to dosing interval.
次要结局
- Parts 1, 2 and 3: Elimination Half-Life (t1/2)(Up to 2 years 6 months)
- Parts 1 and 2: Accumulation Ratio (R)(Up to 2 years 6 months)
- Parts 3 and 4: Average Concentration (Cavg) of JNJ-63723283(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4: Duration of Response (DOR) per irRC(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4 : Number of Participants With Adverse Events (AEs) as a Measure of Safety(Up to 2 years 6 months)
- Parts 1 and 2: Total Systemic Clearance of (CL)(Up to 2 years 6 months)
- Parts 1 and 2: Volume of Distribution at Steady-State (Vss)(Up to 2 years 6 months)
- Parts 3 and 4: Concentration Observed at the Last Timepoint Prior to Dosing (Ctrough)(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4: Overall Response Rate (ORR) per Immune-Related Response Criteria (irRC)(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4: Duration of Response (DOR) per RECIST v1.1(Up to 2 years 6 months)
- Parts 1, 2 and 3, and 4: Maximum Observed Serum Concentration (Cmax)(Up to 2 years 6 months)
- Parts 1 and 2: Area Under the Serum Concentration Versus Time Curve Between time t1 and t2 (AUC [t1-t2])(Up to 2 years 6 months)
- Parts 3 and 4: Area Under the Serum Concentration Versus Time Curve Between Time Zero and Time t (AUC [0-t])(Up to 2 years 6 months)
- Parts 3: Area Under the Serum Concentration Versus Time Curve from Time Zero to Infinity (AUC [0-Infinity])(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4: Presence of Anti-JNJ-63723283 Antibodies and Effect on Serum JNJ-63723283 Concentrations(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4: Clinical Benefit Rate (CBR) per RECIST v1.1(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4: Overall Survival (OS)(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4: Clinical Benefit Rate per irRC(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4: Progression-free Survival (PFS) per RECIST v1.1(Up to 2 years 6 months)
- Parts 1, 2, 3, and 4: Progression-free Survival (PFS) per irRC(Up to 2 years 6 months)