NCT05848739进行中（未招募）1 期
A Phase 1-2 Dose-escalation and Expansion Study of ST316 in Subjects With Selected Advanced Unresectable and Metastatic Solid Tumors
Sapience Therapeutics19 个研究点 分布在 1 个国家目标入组 130 人开始时间: 2023年6月5日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 130
- 试验地点
- 19
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
This is an open-label, two-part, phase 1-2 study designed to determine the safety, tolerability, PK, pharmacodynamics (PD), and proof-of-concept efficacy of ST316 administered IV in subjects with selected advanced solid tumors likely to harbor abnormalities of the WNT/β-catenin signaling pathway. The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.
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
- •Able and willing to sign an informed consent form (ICF) and comply with the protocol and the restrictions and assessments therein.
- •Male or female ≥18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Must have a locally advanced or metastatic inoperable tumor as follows:
- •For the dose-escalation phase: CRC, HCC, TNBC, NSCLC, OC, melanoma, CCA, and SS.
- •For the expansion phase: CRC. Note: if additional indications and combinations are added inclusion/
排除标准
- •will be updated.
- •Agrees to provide a newly obtained biopsy of an accessible lesion (if they can be biopsied based on the Investigator's assessment) prior to the start of study treatment, and to repeat biopsy once during study treatment. Tissue obtained for the biopsy must not be previously irradiated, but a new or progressing lesion in the radiation field is acceptable. Subjects without accessible lesion for biopsy must be able to provide an archival tumor tissue sample for central lab analysis.
- •In the Investigator's opinion, the subject may not derive clinical benefit from, or is ineligible for, a particular form of standard therapy on medical grounds, or the subject failed or did not tolerate one or more of other anticancer therapies:
- •a. For the dose escalation phase: i. Refractory, intolerant, or refused available standard-of-care therapies. ii. Up to three previous lines of systemic anticancer therapies for metastatic disease are allowed (adjuvant or neoadjuvant setting do not count as lines of systemic therapy).
- •iii. Subjects with TNBC or OC with known BRCA mutations must have been previously treated with or intolerant to Food and Drug Administration (FDA) approved treatments prior to enrolling in this study (e.g., iPARP).
- •iv. Subjects with OC must have been treated with, refused, or were ineligible for treatment with bevacizumab to enroll.
- •v. Subjects with CRC tumors that are MSI-H/dMMR must have received, refused or be intolerant to a checkpoint inhibitor (CPI).
- •vi. Subjects with HCC must have confirmed diagnosis of inoperable hepatocellular carcinoma by histology or clinical/radiological criteria. No more than two prior lines of systemic therapy only and Child Pugh Score A or B
- •b. For the expansion phase: i. For all cohorts: Subjects with MSI-H/dMMR must have received, refused or be intolerant to a CPI.
- •ii. Cohort 1 ST316 monotherapy: CRC that has progressed after or on treatment with all of the following, alone or in combination, comprising a maximum of four prior lines of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan, fluoropyrimidines, anti-vascular-endothelial growth factor (VEGF), anti-epidermal growth factor receptor (EGFR) targeted agents (as indicated).
- •iii. Cohort 2: Combination with standard of care (SOC) FOLFIRI + bevacizumab: CRC that has progressed after or on treatment with all of the following, alone or in combination, comprising a maximum of one prior line of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF. Subjects with RAS wild-type must have been treated with an anti-EGFR targeted agent during the first line of treatment.
- •iv. Cohort 3: Combination with fruquintinib: CRC that has progressed after or on treatment with all of the following, alone or in combination, comprising a maximum of two prior lines of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan, fluoropyrimidines or anti-VEGF Subjects with RAS wild-type must have been treated with an anti-EGFR targeted agent during the first or second line of treatment.
- •v. Cohort 4: Combination with Lonsurf + beva: CRC that has progressed after or on treatment with all of the following, alone or in combination, comprising a maximum of two prior lines of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan, fluoropyrimidines or anti-VEGF Subjects with RAS wild-type must have been treated with an anti-EGFR targeted agent during the first or second line of treatment.
- •Exclusion Criteria:
- •Known hypersensitivity to ST316 or any of its excipients.
- •Known hypersensitivity to bevacizumab, 5-FU, leucovorin or irinotecan for Cohort 2, to fruquintinib for Cohort 3 and trifluridine or tipiracil for Cohort 4 in the expansion.
- •Corrected interval between Q and T wave on electrocardiogram (ECG) (QTc) > 480 msec using Fredericia's formula.
- •Symptomatic ascites or pleural effusion. A subject who is clinically stable for 4 weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks prior to study entry and have no evidence of new or enlarging brain metastases. Subjects with treated brain metastases must also follow the steroid exclusion criterion (#11) listed below.
- •For expansion phase only: presence of any other active malignancy requiring systemic therapy other than the disease under study.
- •For subjects to be treated with a regimen containing bevacizumab:
- •History of cardiac disease: congestive heart failure (CHF) ≥NYHA Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring anti-arrhythmic therapy (βeta blockers or digoxin are permitted).
- •Current uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic pressure >90 mmHg despite optimal medical management) as well as prior history of hypertensive crisis or hypertensive encephalopathy.
- •History of arterial thrombotic or embolic events (within 6 months prior to study entry).
- •Significant vascular disease (e.g., aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease).
- •Evidence of bleeding diathesis or clinically significant coagulopathy.
- •Major surgical procedure (including open biopsy, significant traumatic injury, etc.) within 28 days, or anticipation of the need for major surgical procedure during the course of the study as well as minor surgical procedure (excluding placement of a vascular access device or bone marrow biopsy) within 7 days prior to study enrollment.
- •Proteinuria at screening as demonstrated by urinalysis with proteinuria ≥2+ (subjects discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in 24 hours to be eligible).
- •History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intraabdominal abscess within 6 months.
- •Ongoing serious, non-healing wound, ulcer, or bone fracture.
- •History of reversible posterior leukoencephalopathy syndrome (RPLS).
- •History of hypersensitivity to Chinese hamster ovary (CHO) cells or other human or humanized recombinant antibodies.
研究组 & 干预措施
ST316 & Lonsurf + Bevacizumab Combination CRC Expansion phase
Experimental
ST316 & Lonsurf & bevacizumab n=15-30
干预措施: ST316 (Drug)
ST316 & Lonsurf + Bevacizumab Combination CRC Expansion phase
Experimental
ST316 & Lonsurf & bevacizumab n=15-30
干预措施: Lonsurf & bevacizumab (Drug)
Dose Escalation Phase
Experimental
The dose cohorts will be 0.5, 1, 2, 4, 8 & 12 mg/kg IV once weekly (QW)
干预措施: ST316 (Drug)
ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase
Experimental
ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase n=15-30
干预措施: ST316 (Drug)
ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase
Experimental
ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase Expansion phase n=15-30
干预措施: ST316 (Drug)
ST316 & Fruquintinib Combination CRC Expansion phase
Experimental
ST316 & Fruquintinib Combination CRC Expansion phase n=15-30
干预措施: ST316 (Drug)
ST316 & Fruquintinib Combination CRC Expansion phase
Experimental
ST316 & Fruquintinib Combination CRC Expansion phase n=15-30
干预措施: Fruquintinib (Drug)
ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase
Experimental
ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase Expansion phase n=15-30
干预措施: FOLFIRI regimen & bevacizumab (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
时间窗: 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
次要结局
- ST316 PK parameter Cmax(3 years)
- ST316 PK parameter t1/2(3 years)
- ST316 PK parameter AUCt(3 years)
- ST316 Assessment DOR(3 years)
- ST316 PK parameter AUC∞(3 years)
- ST316 PK parameter tmax.(3 years)
- ST316 Assessment Overall survival (OS)(3 Years)
- ST316 Assessment Progression-free survival (PFS)(3 Years)
- ST316 Assessment Objective Response Rate (ORR)(3 Years)
研究者
研究点 (19)
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相关资讯
Sapience Therapeutics Reports 47% Response Rate for First-in-Class β-Catenin Antagonist ST316 in Second-Line Colorectal Cancer- Sapience Therapeutics announced first clinical results from its Phase 2 study of ST316, a first-in-class β-catenin antagonist, showing a 47% objective response rate in second-line colorectal cancer patients.
- The study demonstrated a 93% disease control rate in 15 patients treated with ST316 combined with standard-of-care FOLFIRI plus bevacizumab, significantly outperforming historical controls.
- ST316 targets the Wnt/β-catenin pathway that drives over 80% of colorectal cancers, representing a breakthrough after decades of failed attempts to develop Wnt-targeted therapies.
- The company plans to advance ST316 into additional studies, including a Phase 1b monotherapy trial for familial adenomatous polyposis, which currently has no approved treatments.4 months agoFDA Grants Orphan Drug Designation to Sapience Therapeutics' ST316 for Familial Adenomatous Polyposis- The FDA has granted Orphan Drug Designation to ST316, a β-catenin antagonist, for treating familial adenomatous polyposis (FAP).
- ST316 is a first-in-class drug designed to selectively inhibit the Wnt/β-catenin signaling pathway, crucial in FAP and colorectal cancer.
- The designation provides Sapience Therapeutics with incentives, including potential grants, tax credits, and marketing exclusivity.
- ST316 is currently in Phase 2 trials for colorectal cancer, with ongoing studies exploring its safety and efficacy.last yearSapience Therapeutics Doses First Patient in Phase 2 Trial of ST316 for Colorectal Cancer- Sapience Therapeutics has dosed the first patient in its Phase 2 dose expansion study of ST316, a first-in-class β-catenin antagonist, for colorectal cancer.
- The Phase 2 trial will evaluate ST316 in combination with standard of care treatments across multiple lines of therapy for CRC patients.
- ST316 is designed to selectively inhibit the Wnt/β-catenin signaling pathway in tumor cells, offering a targeted approach to cancer treatment.
- The trial follows promising Phase 1 results demonstrating ST316's potential as an effective therapy for Wnt pathway-driven cancers with a favorable safety profile.last year