A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX202 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 30
- 主要终点
- Incidence of changes in clinical laboratory values (Phase 1 only)
研究概览
简要总结
A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX202 in Patients with 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, and efficacy of XTX202, an engineered IL-2 prodrug with its activity masked, as monotherapy in patients with advanced solid tumors.
Phase 1 Part 1a will examine XTX202 monotherapy in an accelerated and standard 3+3 dose-escalation design. Based on the results of Part 1a, Part 1b will be initiated to further examine XTX202 in patients with select advanced solid tumors and to further characterize XTX202.
Based on results of Phase 1 patients with select advanced solid tumors will be enrolled in Phase 2.
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
- •Disease Criteria
- •Phase 1, Part 1a: Any histologically or cytologically confirmed solid tumor malignancy that is locally advanced or metastatic and has failed standard therapy, or standard therapy is not curative or available
- •Phase 1, Part 1b: Histologically or cytologically confirmed solid tumor malignancy with one of the following tumor histologies: RCC of clear cell histology only, melanoma, squamous cell skin carcinoma, ovarian cancer, non-small cell lung cancer. Those patients who previously received immunotherapy must have derived benefit from this treatment. Additionally, patients with any of the above histologies in an advanced setting who plan to undergo debulking surgery or oligometastasectomy may be eligible to receive 2 cycles of XTX202 treatment in a "window of opportunity" subcohort".
- •Phase 2, Part 2a: Patients with metastatic RCC who have previously been treated with an anti-PD-1 and a TKI, per local and institutional SOC. Patients must have progressed on treatment with an anti-PD-1 mAb administered either as monotherapy or in combination with other therapies
- •Phase 2, Part 2b: Patients with unresectable or metastatic melanoma who have previously been treated with at least 1 prior line of therapy in the recurrent or metastatic setting. Prior therapy must have included an anti-PD-1 alone or in combination per local and institutional standard of care, and patient must have progressed on checkpoint inhibitor therapy. Patients with BRAF V600-activating mutation must have previously received targeted therapy per local and institutional standard of care.
- •ECOG performance status of 0 or 1
- •Adequate organ function
- •Part 1b only patients must be willing to provide fresh tumor biopsies before and after initiation of study treatment.
排除标准
- •Received prior treatment with IL-2 therapy
- •History of clinically significant pulmonary disease
- •History of clinically significant cardiovascular disease
- •Has a diagnosis of immunodeficiency
- •Has an active autoimmune disease that has required systemic treatment in past 2 years, including the use of disease modifying agents, corticosteroids or immunosuppressive drugs
- •Has an active infection requiring systemic therapy within 4 weeks prior to study treatment
研究组 & 干预措施
Phase 2 XTX202 Dose Expansion
Part 2A will enroll patients with metastatic renal cell carcinoma who have progressed following standard-of-care treatment.
Part 2B will enroll patients with melanoma who have progressed following standard-of-care treatment.
干预措施: XTX202 (Drug)
Phase 1 XTX202 Dose Escalation and Pharmacodynamics Expansion
Part 1A Dose Escalation of XTX202 administered in ascending doses to patients with advanced or metastatic solid tumors to find the recommended phase 2 doses (RP2Ds).
Part 1B Evaluation of XTX202 in patients with selected advanced solid tumors to further characterize the pharmacodynamic profile of XTX202
干预措施: XTX202 (Drug)
结局指标
主要结局
Incidence of changes in clinical laboratory values (Phase 1 only)
时间窗: Up to 24 months
Incidence of Dose Limiting Toxicities (DLTs) (Phase 1 Part 1A only)
时间窗: Cycle 1 day 1 up to just prior to the second dose of study drug at Cycle 2 day 1 (each cycle is 21 days)
Investigator-assessed objective response rate (ORR) per RECIST 1.1 (Phase 2 only)
时间窗: Up to 24 months
Incidence of treatment-emergent adverse events (Phase 1 only)
时间窗: Up to 24 months
次要结局
- Systemic clearance (CL)(Up to Cycle 7 (21 days per cycle))
- Volume of distribution (Vd)(Up to Cycle 7 (21 days per cycle))
- Antidrug antibody (ADA) occurrence and titer in serum (Phase 1 only)(Up to 24 months)
- Disease control rate (Phase 2 only)(Up to 24 months)
- Area under the curve (AUC)(Up to Cycle 7 (21 days per cycle))
- Plasma concentrations of XTX202 (total and intact)(Up to Cycle 7 (21 days per cycle))
- Time of maximum observed concentration (Tmax)(Up to Cycle 7 (21 days per cycle))
- Investigator-assessed objective response rate (ORR) per RECIST 1.1 (Phase 1 only)(Up to 24 months)
- Duration of response (DOR) (Phase 2 only)(Up to 24 months)
- Overall survival (OS) (Phase 2 only)(Up to 24 months)
- Maximum observed plasma concentration (Cmax)(Up to Cycle 7 (21 days per cycle))
- Trough concentrations (Ctrough)(Up to Cycle 7 (21 days per cycle))
- Half-life (T1/2)(Up to Cycle 7 (21 days per cycle))
- Progression-free survival (PFS) (Phase 2 only)(Up to 24 months)
- Incidence of treatment-emergent adverse events (Phase 2 only)(Up to 24 months)
- Incidence of changes in clinical laboratory values (Phase 2 only)(Up to 24 months)