A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of Vilastobart (XTX101) Monotherapy and Vilastobart (XTX101) and Atezolizumab Combination Therapy in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 125
- 试验地点
- 35
- 主要终点
- Incidence of changes in clinical laboratory abnormalities in Part 1
研究概览
简要总结
This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety and tolerability of vilastobart (XTX101) as monotherapy and vilastobart (XTX101) and atezolizumab combination therapy 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 and tolerability of vilastobart (XTX101), a tumor-selective anti-CTLA-4 antibody, as monotherapy and vilastobart (XTX101) and atezolizumab combination therapy in patients with advanced solid tumors.
Part 1A will examine vilastobart (XTX101) monotherapy in an accelerated and standard 3+3 dose escalation design. Based on the results of Part 1A, patients with select advanced solid tumors will be enrolled in Part 1B, which will evaluate vilastobart (XTX101) monotherapy in relation to specific PD biomarkers.
Part 1C will examine vilastobart (XTX101) in combination with atezolizumab in a standard 3+3 dose escalation/dose de-escalation design. Part 1C may include a dose expansion cohort to further evaluate the safety, PK, and PD of dose levels that were previously cleared.
Phase 2 will examine vilastobart (XTX101) in combination with atezolizumab in patients with metastatic microsatellite stable colorectal cancer (MSS CRC) at the RP2D(s) defined in Part 1C.
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 -
- •Part 1A and 1C: 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;
- •Any histologically or cytologically confirmed solid tumor malignancy for which anti-PD-1 or anti-PD-L1 treatment is approved and has progressed on or after prior anti-PD-1 or anti-PD-L1 therapy.
- •Patients with metastatic castrate-resistant prostate cancer if they have progressed on at least 2 lines of systemic therapy
- •Patients with extensive stage small cell lung cancer (SCLC) after at least 1 line of prior therapy
- •Patients with microsatellite stable colorectal cancer after at least 2 lines of prior therapy
- •Phase 2: Patients with histologically confirmed metastatic MSS CRC are eligible to enroll in Phase 2 as follows:
- •Patients must have had at least 1 prior chemotherapy regimen for metastatic CRC including all of the following agents: a fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab or biosimilars, an anti epidermal growth factor receptor antibody (cetuximab or panitumumab), and v-raf murine sarcoma viral oncogene homolog B1 inhibitor/BRAF (encorafenib), if applicable
- •Patients with MSI-H/dMMR are excluded
- •ECOG performance status of 0 or 1
- •Adequate organ function
- •Part 1B, Part 1C, and Phase 2 only: measurable disease per iRECIST
排除标准
- •Received prior treatment with anti-CTLA-4 therapy
- •Received prior immune-checkpoint therapy and experienced Grade 3 or greater toxicity lasting greater than 6 weeks
- •Received prior approved systemic anticancer therapy within 4 weeks prior to study treatment
- •Received prior radiotherapy within 2 weeks prior to study treatment
- •Phase 2 only: Received prior anti-PD-1/L1 therapy or any investigational checkpoint inhibitory therapy
- •Has a diagnosis of immunodeficiency
- •Has known malignancy (other than disease under study) that is progressing or has required active treatment within the past 3 years
- •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 intravenous therapy within 4 weeks prior to study treatment, or oral therapy within 2 weeks prior to study treatment
- •Has a history of severe hypersensitivity reaction (≥ Grade 3) to any study intervention and/or any of its excipients
- •Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
- •Phase 2 only: symptomatic bowel obstruction
研究组 & 干预措施
Part 1B - Pharmacodynamic (PD) Dose Expansion
Part 1B vilastobart (XTX101) at the RP2D will be administered to further examine vilastobart (XTX101) as monotherapy in patients with select advanced solid tumors.
干预措施: vilastobart (XTX101) (Drug)
Part 1A - vilastobart (XTX101) Monotherapy Dose Escalation
Part 1A Dose Escalation of vilastobart (XTX101) administered in ascending doses to patients with advanced or metastatic solid tumors to find the recommended phase 2 dose (RP2D).
干预措施: vilastobart (XTX101) (Drug)
Part 1C - vilastobart (XTX101) Dose Escalation and Dose Expansion in Combination with Atezolizumab
Part 1C will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101).
干预措施: vilastobart (XTX101) (Drug)
Phase 2 - vilastobart (XTX101) Dose Expansion in Combination with Atezolizumab
Phase 2 will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101) at the RP2D(s) in patients with MSS CRC.
干预措施: Atezolizumab (Drug)
Part 1C - vilastobart (XTX101) Dose Escalation and Dose Expansion in Combination with Atezolizumab
Part 1C will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101).
干预措施: Atezolizumab (Drug)
Phase 2 - vilastobart (XTX101) Dose Expansion in Combination with Atezolizumab
Phase 2 will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101) at the RP2D(s) in patients with MSS CRC.
干预措施: vilastobart (XTX101) (Drug)
结局指标
主要结局
Incidence of changes in clinical laboratory abnormalities in Part 1
时间窗: Up to 24 months
Investigator-assessed objective response rate (ORR) per iRECIST in Phase 2
时间窗: Up to 24 months
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 at Cycle 2 day 1 (approximately 3 weeks)
Incidence of treatment-emergent adverse events in Part 1
时间窗: Up to 24 months
Incidence of Dose Limiting Toxicities (DLTs) in Part 1C
时间窗: Cycle 1 Day 1 up to Cycle 3 Day 1 (approximately 6 weeks)
次要结局
- Disease control rate in Phase 2(Up to 24 months)
- Investigator-assessed objective response rate (ORR) per iRECIST in Part 1(Up to 24 months)
- Antidrug antibody (ADA) occurrence and titer in serum in Part 1(Up to 24 months)
- Plasma concentrations of vilastobart (XTX101) (total and intact) in Part 1 and Phase 2(Up to 24 months)
- Maximum observed plasma concentration (Cmax) in Part 1 and Phase 2(Up to 24 months)
- Time of maximum observed concentration (Tmax) in Part 1 and Phase 2(Up to 24 months)
- Trough concentrations (Ctrough) in Part 1 and Phase 2(Up to 24 months)
- Area under the curve (AUC) in Part 1 and Phase 2(Up to 24 months)
- Half-life (T1/2) in Part 1 and Phase 2(Up to 24 months)
- Systemic clearance (CL) in Part 1 and Phase 2(Up to 24 months)
- Volume of distribution (Vd) in Part 1 and Phase 2(Up to 24 months)
- Investigator-assessed ORR per RECIST in Phase 2(Up to 24 months)
- Progression-free survival per iRECIST in Phase 2(Up to 24 months)
- Overall survival in Phase 2(Up to 24 months)
- Incidence of treatment-emergent AEs in Phase 2(Up to 24 months)
- Incidence of changes in clinical laboratory abnormalities in Phase 2(Up to 24 months)
- Duration of response per iRECIST in Phase 2(Up to 24 months)