A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX501 in Participants With Metastatic Non-Small Cell Lung Cancer and Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 140
- 主要终点
- Incidence of Dose Limiting Toxicities (DLTs) in Part 1A
研究概览
简要总结
This is a first-in-human, multicenter, Phase 1/2, open-label study designed to evaluate the safety and tolerability of XTX501 as monotherapy in participants with metastatic non-small cell lung cancer (NSCLC) and select advanced solid tumors.
详细描述
This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety, tolerability, PK, pharmacodynamics, immunogenicity, and antitumor activity of XTX501, an investigational bispecific PD-1/masked IL-2 in participants with metastatic NSCLC and select advanced solid tumors.
Phase 1, Part 1A will examine XTX501 monotherapy in a Bayesian Optimal Interval design to determine the maximum tolerated dose up to 10 dose regimens.
Phase 1, Part 1B will further evaluate the safety and antitumor activity of XTX501 at dose regimens under consideration for the recommended Phase 2 dose(s).
Phase 2 will further evaluate the efficacy of the selected recommended Phase 2 dose(s).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Measurable disease at baseline per RECIST v1.1
- •ECOG performance status of 0 or 1
- •Adequate organ function
- •Metastatic NSCLC:
- •Must have histologically confirmed metastatic NSCLC.
- •Tumor must have been assessed for EGFR and ALK per local standard of practice; patients with these driver mutations are excluded.
- •Patients with tumors known to have the following alterations are excluded: ROS1, RET, MET, HER-2, NTRK 1/2/
- •Patients must have previously derived clinical benefit from a PD-1/PD-L1 inhibitor or PD-1/PDL-1 bispecific without progression for at least 6 months.
排除标准
- •Prior treatment with IL-2
- •History of significant pulmonary disease
- •History of clinically significant cardiovascular disease
- •Active CNS metastases
- •Pregnant or breastfeeding
- •In Phase 1, participants with select additional solid tumor types may be enrolled.
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLTs) in Part 1A
时间窗: Cycle 1 Day 1 up to just prior to the second dose of study drug (approximately 21 days)
Incidence of treatment-emergent adverse events (Phase 1 and Phase 2)
时间窗: Up to Safety Follow Up Period (90 [+7] days after the last dose)
Incidence of serious adverse events (Phase 1 and Phase 2)
时间窗: Up to Safety Follow Up Period (90 [+7] days after the last dose)
Incidence of significant change from baseline in clinical laboratory values (Phase 1 and Phase 2)
时间窗: Up to Safety Follow Up Period (90 [+7] days after the last dose)
Investigator-assessed objective response rate (ORR) per RECIST v1.1 (Phase 2)
时间窗: Up to Safety Follow Up Period (90 [+7] days after the last dose)
次要结局
- Investigator-assessed objective response rate (ORR) per RECIST v1.1 (Phase 1)(Up to Safety Follow Up Period (90 [+7] days after the last dose))
- Investigator-assessed duration of response (DOR) per RECIST v1.1 (Phase 1 and Phase 2)(Up to Safety Follow Up Period (90 [+7] days after the last dose))
- Investigator-assessed disease control rate (DCR) per RECIST v1.1 (Phase 2)(Up to Safety Follow Up Period (90 [+7] days after the last dose))
- Investigator-assessed progression free survival (PFS) per RECIST v1.1 (Phase 2)(Up to Safety Follow Up Period (90 [+7] days after the last dose))
- Incidence and persistence of antidrug antibodies (ADAs) (Phase 1 and Phase 2)(Up to End of Treatment (within 10 days of the decision to discontinue XTX501))
- Maximum observed plasma concentration (Cmax) (Phase 1 and Phase 2)(Up to End of Treatment (within 10 days of the decision to discontinue XTX501))
- Time of maximum observed concentration (Tmax) (Phase 1 and Phase 2)(Up to End of Treatment (within 10 days of the decision to discontinue XTX501))
- Trough concentrations (Ctrough) (Phase 1 and Phase 2)(Up to End of Treatment (within 10 days of the decision to discontinue XTX501))
- Area under the curve (AUC) (Phase 1 and Phase 2)(Up to End of Treatment (within 10 days of the decision to discontinue XTX501))
- Half-life (t1/2) (Phase 1 and Phase 2)(Up to End of Treatment (within 10 days of the decision to discontinue XTX501))
- Systemic clearance (CL) (Phase 1 and Phase 2)(Up to End of Treatment (within 10 days of the decision to discontinue XTX501))
- Volume of distribution (Vd) (Phase 1 and Phase 2)(Up to End of Treatment (within 10 days of the decision to discontinue XTX501))