A Phase 1a/1b Dose Escalation and Dose Expansion Study of NPX887 in Participants With Solid Tumor Malignancies Known to Express HHLA-2/B7-H7
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 144
- 试验地点
- 8
- 主要终点
- Incidence of dose limiting toxicity (DLT)
研究概览
简要总结
NPX887 is a human, antagonistic immunoglobulin G1 (IgG1) monoclonal antibody targeting B7-H7 (HHLA2) that may potentiate an anti-tumor immune response. The goal of this first-in-human study is to learn whether NPX887 is safe and tolerable and shows a preliminary efficacy in participants with B7-H7 (HHLA2) expressing tumors at selected dose(s). The main questions it aims to answer are:
- what is an appropriate dose to be given to participants?
- are the side effects of treatment manageable?
- what is the preliminary anti-tumor activities?
Participants who are treated will receive an intravenous (IV) infusion of NPX887 if their disease has not progressed, and be closely monitored by the treating physicians.
详细描述
This study is comprised of Phase 1a (Dose Escalation) and Phase 1b including Part 1b (Dose Expansion) and Part 1c (Randomized Dose Comparison). Phase 1a will test different doses of NPX887 to determine the optimal dose(s) to continue with in Phase 1b. In the Phase 1b, more participants will be tested to evaluate preliminary activities in multiple disease-specific cohorts and compare the efficacy of the higher and lower doses chosen in Phase 1a.
Throughout the study, safety and preliminary efficacy data will be collected to characterize the clinical activity of NPX887. Samples of blood will be taken to help in an understanding of how NPX887 behaves in the body by assessing the amount of drug in the blood over time, and changes in blood components. Tumor tissue samples will be collected at screening and on-treatment stages for biomarker analysis and pharmacodynamics (PD) evaluation.
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
- •Histologically or cytologically confirmed recurrent, metastatic solid tumor refractory to, or intolerant of, standard of care therapy in one of the following indications:
- •Phase 1a (Dose Escalation): Non-small cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), renal cell carcinoma (RCC), colorectal carcinoma (CRC), gastric and gastro-esophageal carcinoma, esophageal adenocarcinoma, biliary tract cancers, ovarian carcinoma, and other solid tumor types known to express B7-H7/HHLA
- •Phase 1b including Part 1b (Dose Expansion) and Part 1c (Randomized Dose Comparison): participants who have clear cell RCC, EGFR mutant lung adenocarcinoma, or gastric/GEJ adenocarcinoma.
- •In Phase 1b, participants must have confirmed B7-H7/HHLA2 expression in their tumor determined via archival tissue IHC testing through a central lab (pre-screening).
- •Phase 1a: Evaluable disease (measurable or non-measurable) by RECIST v.1.1 criteria; Phase 1b: Measurable disease by RECIST v1.1 criteria with additional disease-specific enrollment criteria applied to clear cell RCC, EGFR mutant lung adenocarcinoma, or gastric/GEJ adenocarcinoma.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or
- •Ability to understand and the willingness to sign a written informed consent document
- •Willing to use highly effective contraceptive measures throughout the trial.
排除标准
- •Treatment with any of the following:
- •Systemic anticancer treatment ≤14 days or within 5 half-lives prior to the first dose of study drug, whichever is shorter.
- •Limited-field radiotherapy ≤7 days or extended-field thoracic radiotherapy ≤8 weeks of the first dose of study drug.
- •Have any unresolved toxicity of ≥Grade 2 from previous anti-cancer treatment, except for alopecia, chronic stable neuropathy for >4 months, changes in skin pigmentation, or requiring replacement therapy for endocrine abnormalities.
- •Participants with known brain metastases are excluded unless they are clinically stable, with no new or enlarging brain metastases as evidenced on MRI during screening.
- •History of Grade 3 immune-related pneumonitis or colitis.
- •Participants who discontinued prior immunotherapy due to immune-related toxicities, or history of unresolved prior immune-related toxicity except for endocrine abnormalities requiring replacement therapy or vitiligo.
- •Known autoimmune disease requiring immunosuppressive treatment requiring the equivalent of more than 10 mg prednisone daily.
研究组 & 干预措施
NPX887 Treatment
Participants will receive NPX887 by IV infusion every 3 weeks.
干预措施: NPX887 (Drug)
结局指标
主要结局
Incidence of dose limiting toxicity (DLT)
时间窗: From first dose through 21 days
Number of participants with DLT in Ph1a
Disease control rate (DCR)
时间窗: Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
The proportion of participants with a best ORR + Stable Disease (SD) in Ph1b
Incidence of treatment-emergent adverse events (AEs)
时间窗: From first dose up to 24 months
Number and type of AEs categorized by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 in Ph1a
Incidence of discontinuations, dosing interruptions, and dose reductions
时间窗: From first dose up to 24 months
Number of participants with changes to their dosing schedule as a result of treatment-related AEs in Ph1a
Objective response rate (ORR)
时间窗: Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
The proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 in Ph1b
Duration of response (DOR)
时间窗: Up to 2 years or until progressive disease, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
The time interval from first occurrence of a documented objective response to the time of disease progression as determined by the Investigator using RECIST 1.1 or death from any cause, whichever comes first, in Ph1b
Progression-free Survival (PFS)
时间窗: Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.
The duration from the start of treatment until tumor progression or death of any cause in Ph1b
次要结局
- Area under the concentration curve (AUC0-24) of NPX887(Following dosing on day 1 of each 21-day treatment cycles up to Cycle 7, then on day 1 every 3 cycles, up to end of treatment and 90-day follow-up)
- Maximum plasma concentration (Cmax) of NPX887(Following dosing on day 1 of each 21-day treatment cycles up to Cycle 7, then on day 1 every 3 cycles, up to end of treatment and 90-day follow-up)
- Half-life in blood circulation (T1/2) of NPX887(Following dosing on day 1 of each 21-day treatment cycles up to Cycle 7, then on day 1 every 3 cycles, up to end of treatment and 90-day follow-up)
- Immunogenicity of NPX887(Following dosing on day 1 of each 21-day treatment cycles up to Cycle 4, then on day 1 every 3 cycles, up to 90-day follow-up)
- Overall survival (OS)(From first dose until death from any cause through 24 months)
- Incidence of AEs, DLTs, PD changes within the tumor and in blood(From first dose through 21 days, or up to 24 months)
- ORR, DOR, DCR, and PFS(Up to 2 years or until progressive disease, death, unacceptable toxicity, participant withdraw consent or investigator's decision, whichever occurs first.)