Open-label, Non-randomized, Multi-cohort, Phase 1b/2 Trial Investigating the Safety, Tolerability, and Antitumor Activity of STC-15 (a METTL3 Inhibitor) as a Part of Combination Therapy With Toripalimab in Participants With Selected Advanced Cancers and as Monotherapy in Participants With Selected Sarcomas
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 107
- 试验地点
- 12
- 主要终点
- Combination Cohorts: Safety and tolerability of STC-15 in combination with toripalimab
研究概览
简要总结
This early phase oncology trial will be conducted at various study centers to investigate the safety, tolerability, and antitumor activity of STC-15 (a METTL3 inhibitor) in combination with toripalimab (anti- programmed cell death 1 [PD-1]) in advanced unresectable or metastatic tumors.
The Phase 2 Monotherapy part is an open-label, non-randomized, multicenter Simon's 2-stage design that investigates the safety, tolerability, and antitumor activity of STC-15 in participants with selected, relapsed sarcomas subtypes, dedifferentiated (DD) liposarcoma and leiomyosarcoma (uterine and non-uterine).
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
- •Estimated life expectancy ≥ 3 months.
- •ECOG performance status 0 or
- •Measurable disease according to RECIST v1.1 as assessed by the local site investigator/radiology.
- •Documented radiologic assessment of progression on the prior therapy before study entry.
- •Have adequate organ function.
- •Have the ability to swallow, retain, and absorb oral medication.
- •Inclusion Criteria (Phase 2 Monotherapy Cohorts):
- •Have histologic or cytologic confirmation of advanced sarcoma of the selected histologic subtype that is not amenable to local curative therapy. Participant must have received at least 2, but no more than 4 prior lines of systemic therapy.
- •Pre-treatment and on-treatment biopsy if medically feasible.
排除标准
- •Pregnant and lactating women.
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks or 5 half-lives, whichever is shorter, prior to first IMP administration.
- •Participants who have not recovered from all AEs due to previous therapies to Grade ≤ 1 or baseline, according to NCI-CTCAE v5.
- •Exceptions include: alopecia, Grade ≤ 2 neuropathy, and endocrine-related AEs Grade ≤ 2 who are stable on treatment or hormone replacement.
- •History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or the presence of ongoing pneumonitis/interstitial lung disease).
- •Clinically significant cardiovascular disease or condition.
- •Known active CNS metastases and/or leptomeningeal disease.
研究组 & 干预措施
Phase 2 Stage 1 Monotherapy
STC-15 in patients with DD liposarcoma or leiomyosarcoma
干预措施: STC-15 monotherapy (Drug)
Phase 2 Stage 2 Monotherapy
STC-15 in patients with DD liposarcoma or leiomyosarcoma
干预措施: STC-15 monotherapy (Drug)
Phase 1 dose escalation
Phase 1b 3+3 trial design of dose escalation of STC-15 in combination with toripalimab
干预措施: STC-15 in combination with toripalimab (Combination Product)
结局指标
主要结局
Combination Cohorts: Safety and tolerability of STC-15 in combination with toripalimab
时间窗: 6 months
Incidence of adverse events graded according to CTCAE v5.0
Phase 2 Monotherapy Cohorts: Antitumor activity of STC-15 monotherapy
时间窗: 6 months
ORR according to RECIST
Safety and tolerability of STC-15 in combination with toripalimab
时间窗: 6 months
Incidence of adverse events graded according to CTCAE v5.0
次要结局
- Combination Cohorts: Anti-tumor activity(6 months)
- Combination and Phase 2 Monotherapy Cohorts: Maximum observed plasma concentration of STC-15 (Cmax)(22 days)
- Combination and Phase 2 Monotherapy Cohorts: Calculated time to reach maximum observed plasma concentration (Tmax)(22 days)
- Combination and Phase 2 Monotherapy Cohorts: Calculated area under the plasma concentration-time curve of STC-15 (AUC0-t)(22 days)
- Phase 2 Monotherapy Cohorts: Safety and tolerability of STC-15(6 months)
- Anti-tumor activity(6 months)
- Maximum observed plasma concentration of STC-15 (Cmax)(22 days)
- Recommended Phase 2 Dose(6 months)
- Calculated time to reach maximum observed plasma concentration (Tmax)(22 days)
- Calculated area under the plasma concentration-time curve of STC-15 (AUC0-t)(22 days)