A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors

NCT ID: NCT05848739

Last Updated: 2025-05-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-05

Study Completion Date

2027-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Colon Cancer Metastatic Colon Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation Phase

The dose cohorts will be 0.5, 1, 2, 4, 8 \& 12 mg/kg IV once weekly (QW)

Group Type EXPERIMENTAL

ST316

Intervention Type DRUG

IV

ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase

ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase n=15-30

Group Type EXPERIMENTAL

ST316

Intervention Type DRUG

IV

ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase

ST316 \& FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase Expansion phase n=15-30

Group Type EXPERIMENTAL

ST316

Intervention Type DRUG

IV

FOLFIRI regimen & bevacizumab

Intervention Type DRUG

FOLFIRI: Days 1 and 15 of each 28-day cycle:

* irinotecan 180 mg/m2 IV over 90 minutes concurrently with
* leucovorin 400 mg/m2 IV over 2 hours, and then
* 5-FU bolus 400mg/m2 (up to 15 min infusion)
* 5-FU 2400 mg/m2 IV over 46 hours
* bevacizumab should be administered as 5mg/kg.

ST316 & Fruquintinib Combination CRC Expansion phase

ST316 \& Fruquintinib Combination CRC Expansion phase n=15-30

Group Type EXPERIMENTAL

ST316

Intervention Type DRUG

IV

Fruquintinib

Intervention Type DRUG

5 mg once a day for the first 21 days of a 28-day cycle

ST316 & Lonsurf + Bevacizumab Combination CRC Expansion phase

ST316 \& Lonsurf \& bevacizumab n=15-30

Group Type EXPERIMENTAL

ST316

Intervention Type DRUG

IV

Lonsurf & bevacizumab

Intervention Type DRUG

Lonsurf 35 mg/m2 twice daily on days 1-5 and days 8-12 every 28 day bevacizumab 5 mg/kg on days 1 and 15. ST316

Interventions

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ST316

IV

Intervention Type DRUG

FOLFIRI regimen & bevacizumab

FOLFIRI: Days 1 and 15 of each 28-day cycle:

* irinotecan 180 mg/m2 IV over 90 minutes concurrently with
* leucovorin 400 mg/m2 IV over 2 hours, and then
* 5-FU bolus 400mg/m2 (up to 15 min infusion)
* 5-FU 2400 mg/m2 IV over 46 hours
* bevacizumab should be administered as 5mg/kg.

Intervention Type DRUG

Fruquintinib

5 mg once a day for the first 21 days of a 28-day cycle

Intervention Type DRUG

Lonsurf & bevacizumab

Lonsurf 35 mg/m2 twice daily on days 1-5 and days 8-12 every 28 day bevacizumab 5 mg/kg on days 1 and 15. ST316

Intervention Type DRUG

Other Intervention Names

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FOLFIRI

Eligibility Criteria

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Inclusion Criteria

1. Able and willing to sign an informed consent form (ICF) and comply with the protocol and the restrictions and assessments therein.
2. Male or female ≥18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
4. Must have a locally advanced or metastatic inoperable tumor as follows:

1. For the dose-escalation phase: CRC, HCC, TNBC, NSCLC, OC, melanoma, CCA, and SS.

Exclusion Criteria

5. 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.
6. 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 B7.

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.


1. Known hypersensitivity to ST316 or any of its excipients.
2. 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.
3. Corrected interval between Q and T wave on electrocardiogram (ECG) (QTc) \> 480 msec using Fredericia's formula.
4. 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.
5. 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.
6. For expansion phase only: presence of any other active malignancy requiring systemic therapy other than the disease under study.
7. For subjects to be treated with a regimen containing bevacizumab:

1. 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).
2. 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.
3. History of arterial thrombotic or embolic events (within 6 months prior to study entry).
4. Significant vascular disease (e.g., aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease).
5. Evidence of bleeding diathesis or clinically significant coagulopathy.
6. 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.
7. 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).
8. History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intraabdominal abscess within 6 months.
9. Ongoing serious, non-healing wound, ulcer, or bone fracture.
10. History of reversible posterior leukoencephalopathy syndrome (RPLS).
11. History of hypersensitivity to Chinese hamster ovary (CHO) cells or other human or humanized recombinant antibodies.

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Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sapience Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Abi Vainstein-Haras

Role: STUDY_CHAIR

CMO

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

Sarah Cannon Research Institute - CO

Denver, Colorado, United States

Site Status RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

START Midwest

Grand Rapids, Michigan, United States

Site Status ACTIVE_NOT_RECRUITING

Westchester Medical Center

Valhalla, New York, United States

Site Status RECRUITING

Duke Universtiy

Durham, North Carolina, United States

Site Status RECRUITING

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Sanford Cancer Center

Sioux Falls, South Dakota, United States

Site Status RECRUITING

Fred Hutch Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Joyce Gakuria

Role: CONTACT

914-418-5100

Facility Contacts

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Ke Hu

Role: primary

205-644-2592

Hu

Role: backup

Stephanie Kim

Role: primary

Tamara Davidson, MD

Role: primary

Nicole Perry

Role: primary

Susan Gottardt

Role: primary

617-667-2100

Allyson Pulsoni

Role: primary

914-493-6610

JoAnna Gontarz, MSN

Role: primary

Christina Caldwell

Role: primary

Staci Vogel

Role: primary

605-312-3320

Erika Kalberer

Role: primary

206-606-5886

Other Identifiers

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ST316-101

Identifier Type: -

Identifier Source: org_study_id

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