A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SNS-101 (Anti VISTA) as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 10
- 主要终点
- Objective Response Rate (ORR) - Part C. Part C was never initiated.
研究概览
简要总结
Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101, a novel anti VISTA IgG1 monoclonal antibody as monotherapy or in combination with cemiplimab in patients with advanced solid tumors.
详细描述
This is a first-in-human, Phase 1/2 open-label, multi-center, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101, a novel anti VISTA IgG1 monoclonal antibody as monotherapy or in combination with cemiplimab in patients with advanced solid tumors.
The Phase 1 portion is conducted in two parts; A and B: Phase 2 is planned in Part C.
- Part A: Phase 1 Monotherapy Dose Escalation and Dose Expansion (SNS-101 alone)
- Part B: Phase 1 Combination Dose Escalation and Dose Expansion (SNS-101 in combination with cemiplimab)
Once the dose escalation portion was complete, enrollment expanded to targeted tumor types:
- Approximately 10 patients with colorectal cancer (CRC) will be enrolled in the Monotherapy Dose Expansion.
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
- •Histologically or cytologically documented locally advanced, unresectable or metastatic solid tumor.
- •Having received and failed or was intolerant to standard of care for advanced disease or not eligible for standard of care therapy with the following tumor types for patients in Phase 1 dose expansion cohorts:
- •Microsatellite Stable (MSS) CRC (both monotherapy and combination cohorts); no more than 3 lines of prior systemic therapy for metastatic disease.
- •H&N cancer (combination cohort only); no more than 2 lines of prior systemic therapy for metastatic disease.
- •Melanoma (combination cohort only); no more than 3 lines of prior systemic therapy for metastatic disease, including at least 1 prior treatment with a BRAF inhibitor for patients with a BRAF mutation.
- •NSCLC (combination cohort only); no more than 2 lines of prior systemic therapy for metastatic disease, including at least 1 prior treatment with a targeted therapy for patients with a mutation such as EGFR, ALK, KRAS, or RET.
- •Patients with H&N cancer, melanoma, and NSCLC (or additional tumor types that typically respond to PD1/PD-L1 monotherapy) must have received a prior PD1/PD-L1 where best response was stable disease and progression occurred during treatment or within 3 months of last dose of PD1/PD-L
- •Additional tumor types and doses may be considered.
- •Measurable disease
- •ECOG performance status 0 or
- •Life expectancy of ≥ 3 months.
- •Willing to provide pre-treatment (archival or fresh) and on-treatment tumor biopsy samples.
- •Adequate organ function
- •Women of childbearing potential and fertile males with WOCBP partners must use highly effective contraception during the study and for 180 days after the study. Patients must agree not to donate eggs (ova, oocytes) or sperm during the study.
排除标准
- •Use of anti-PD-1/PD-L1 targeting monoclonal antibody therapy, monoclonal antibody therapy, chemotherapy, biologic, investigational, or radiotherapy within 2 weeks of Cycle 1 Day
- •Clinically significant unresolved toxicities from prior anticancer therapy.
- •Grade 3 or higher immune-related adverse event on prior PD-1/PD-L1 blockade or prior agents targeting stimulatory or co-inhibitory T cell receptor.
- •Known other previous/current malignancy requiring treatment within ≤ 2 years except for limited disease treated with curative intent, such as carcinoma in situ, squamous or basal cell skin carcinoma, or superficial bladder carcinoma.
- •Known asymptomatic or symptomatic brain metastasis or leptomeningeal disease.
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
- •Women who are pregnant or breastfeeding.
研究组 & 干预措施
Part C - Cohort Expansion - SNS-101 alone or in combination with cemiplimab
SNS-101 IV alone or in combination with cemplimab IV every 21 days at the RP2D.
Following completion of the Phase 1 Parts A and B portions of the study, the Phase 2, Part C portion was never initiated. No participants were enrolled in Part C.
干预措施: SNS-101 (anti-VISTA) (Drug)
Part A - SNS-101 Monotherapy Dose Escalation and Dose Expansion
SNS-101 IV alone every 21 days. Patients initially enroll in dose escalation cohorts.
干预措施: SNS-101 (anti-VISTA) (Drug)
Part B - SNS-101 in combination with cemiplimab and Dose Expansion
SNS-101 IV and cemiplimab IV every 21 days. Patients initially enroll in dose escalation cohorts.
干预措施: SNS-101 (anti-VISTA) (Drug)
Part C - Cohort Expansion - SNS-101 alone or in combination with cemiplimab
SNS-101 IV alone or in combination with cemplimab IV every 21 days at the RP2D.
Following completion of the Phase 1 Parts A and B portions of the study, the Phase 2, Part C portion was never initiated. No participants were enrolled in Part C.
干预措施: Cemiplimab (Drug)
Part B - SNS-101 in combination with cemiplimab and Dose Expansion
SNS-101 IV and cemiplimab IV every 21 days. Patients initially enroll in dose escalation cohorts.
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Objective Response Rate (ORR) - Part C. Part C was never initiated.
时间窗: Day 1 through study completion (approximately 1 year).
Measured by RECIST 1.1 and iRECIST
Adverse Events - Part A & B
时间窗: Day 1 through 90 days after the last dose
Incidence, nature and severity of treatment-related adverse events
Determine the Recommended Phase 2 dose or maximum tolerated dose - Part A & B
时间窗: Approximately 15 months
Incidence and nature of dose-limiting toxicities
次要结局
- Determine pharmacokinetic profile (maximum concentration) of SNS-101 - Part A, B.& C. Part C was never initiated.(Day 1 through 30 days after the last dose)
- Determine pharmacokinetic profile (area under the curve) of SNS-101 - Part A, B & C. Part C was never initiated.(Day 1 through 30 days after the last dose)
- Determine pharmacokinetic profile (total clearance) of SNS-101 - Part A, B & C. Part C was never initiated.(Day 1 through 30 days after the last dose)
- Determine pharmacokinetic profile (terminal half life) of SNS-101 - Part A, B & C. Part C was never initiated.(Day 1 through 30 days after the last dose)
- Number of participants with anti-SNS-101 antibodies post-administration of SNS-101 - Part A, B & C. Part C was never initiated.(Day 1 through 30 days after the last dose)
- Duration of Response (DoR) - Part A, B & C. Part C was never initiated.(Day 1 through study completion (approximately 1 year))
- Disease Control Rate (DCR) - Part A, B & C. Part C was never initiated.(Day 1 through study completion (approximately 1 year))
- Progression Free Survival - Part A, B and C. Part C was never initiated.(Day 1 through study completion - approximately 1 year (Part A, B & C))
- Adverse Events - Part C. Part C was never innitiated.(Day 1 through study completion (approximately 1 year))
- Objective Response Rate (ORR) - Part A & B(Day 1 through study completion (approximately 1 year))