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

May 6, 2025 updated by: Sapience Therapeutics

A Phase 1-2 Dose-escalation and Expansion Study of ST316 in Subjects With Selected Advanced Unresectable and Metastatic Solid Tumors

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

130

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama
        • Contact:
          • Hu
        • Contact:
        • Principal Investigator:
          • Nusrat Jahan, MD
    • California
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Usc Norris Comprehensive Cancer Center
        • Principal Investigator:
          • Anthoney El-Khoueiry, MD
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Sarah Cannon Research Institute - CO
        • Principal Investigator:
          • Jason Henry, MD
        • Contact:
    • Louisiana
      • New Orleans, Louisiana, United States, 70123
        • Recruiting
        • Ochsner Clinic Foundation
        • Principal Investigator:
          • Jonathan Mizrahi, MD
        • Contact:
          • Nicole Perry
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
        • Principal Investigator:
          • Bruno Bockorny, MD
        • Contact:
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Active, not recruiting
        • START Midwest
    • New York
      • Valhalla, New York, United States, 10595
        • Recruiting
        • Westchester Medical Center
        • Contact:
        • Principal Investigator:
          • Marjorie Zauderer, MD
    • North Carolina
      • Durham, North Carolina, United States, 27708
        • Recruiting
        • Duke Universtiy
        • Principal Investigator:
          • Niharika Mettu, MD PhD
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • OU Health Stephenson Cancer Center
        • Principal Investigator:
          • Susanna Ulahannan, MD
        • Contact:
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Recruiting
        • Sanford Cancer Center
        • Contact:
        • Principal Investigator:
          • Steven Powell, MD
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutch Cancer Center
        • Principal Investigator:
          • Gabriela Chiorean, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.
    2. For the expansion phase: CRC. Note: if additional indications and combinations are added inclusion/exclusion criteria will be updated.
  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.

Exclusion Criteria:

  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.

      -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation Phase
The dose cohorts will be 0.5, 1, 2, 4, 8 & 12 mg/kg IV once weekly (QW)
Drug: ST316
IV
Experimental: ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase
ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase n=15-30
Drug: ST316
IV
Experimental: 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
Drug: ST316
IV
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.
Other Names:
  • FOLFIRI
Experimental: ST316 & Fruquintinib Combination CRC Expansion phase
ST316 & Fruquintinib Combination CRC Expansion phase n=15-30
Drug: ST316
IV
Drug: Fruquintinib
5 mg once a day for the first 21 days of a 28-day cycle
Experimental: ST316 & Lonsurf + Bevacizumab Combination CRC Expansion phase
ST316 & Lonsurf & bevacizumab n=15-30
Drug: ST316
IV
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ST316 PK parameter AUCt
Time Frame: 3 years
Area under the concentration-time curve over the dosing interval
3 years
ST316 Assessment DOR
Time Frame: 3 years
DOR is defined for participants achieving a confirmed CR+PR as the time from the initial response of CR+PR per investigator review according to RECIST 1.1 criteria to disease progression or death of any cause, whichever occurs earlier
3 years
ST316 PK parameter Cmax
Time Frame: 3 years
Maximum observed serum concentration
3 years
ST316 PK parameter t1/2
Time Frame: 3 years
half life
3 years
ST316 PK parameter AUC∞
Time Frame: 3 years
Area under the concentration-time curve over the dosing interval time from time 0 extrapolated to infinite time
3 years
ST316 PK parameter tmax.
Time Frame: 3 years
The time take to reach Maximum observed serum concentration
3 years
ST316 Assessment Overall survival (OS)
Time Frame: 3 Years
Overall survival (OS) is defined as time from first study treatment to death due to any cause.
3 Years
ST316 Assessment Progression-free survival (PFS)
Time Frame: 3 Years
Progression-free survival (PFS) is defined as time from first study treatment to a documented disease progression according to RECIST version 1.1, as determined by the investigator, or death due to any cause, whichever occurs earlier.
3 Years
ST316 Assessment Objective Response Rate (ORR)
Time Frame: 3 Years
ORR defined as percentage of participants with confirmed best overall response of Confirmed complete response (CR) and partial response (PR) per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
3 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sapience Therapeutics

Investigators

  • Study Chair: Abi Vainstein-Haras, CMO

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 5, 2023

Primary Completion (Estimated)

May 31, 2026

Study Completion (Estimated)

May 31, 2027

Study Registration Dates

First Submitted

March 21, 2023

First Submitted That Met QC Criteria

April 28, 2023

First Posted (Actual)

May 8, 2023

Study Record Updates

Last Update Posted (Actual)

May 11, 2025

Last Update Submitted That Met QC Criteria

May 6, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ST316-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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