A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors
- Conditions
- Colon CancerMetastatic Colon Cancer
- Interventions
- Registration Number
- NCT05848739
- Lead Sponsor
- Sapience Therapeutics
- Brief Summary
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
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 115
-
Able and willing to sign ICF and comply with the protocol and the restrictions and assessments therein.
-
Male or female ≥18 years of age.
-
ECOG performance status 0-1.
-
Must have a locally advanced or metastatic inoperable tumor as follows:
- For the dose escalation/regimen exploration phase: CRC, BC, NSCLC, OC, pancreatic adenocarcinoma, melanoma, CC, and synovial sarcoma.
- For the expansion phase: CRC
-
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.
a. For the dose escalation/regimen exploration phase: i. Refractory, intolerant, or refused all available standard-of-care therapies ii. Up to 3 previous lines of systemic anticancer therapies for metastatic disease are allowed.
iii. Patients with TNBC or OC with known BRCA mutations must have been previously treated with or intolerant to FDA approved treatments prior to enrolling in this study (e.g. iPARP).
iv. Patients with OC must have been treated with, refused, or were ineligible for treatment with bevacizumab to enroll.
v. Patients with CRC tumors that are MSI-H/dMMR must have received, refused or be intolerant to a check point inhibitor.
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 monotherapy: CRC that has progressed after or on treatment with all of the following, alone or in combination, comprising a maximum of 4 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 1 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 3 prior lines of therapy for their advanced/metastatic disease: oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF, regorafenib or lonsurf. Subjects with RAS wild-type must have been treated with an anti-EGFR targeted agent during the first line of treatment.
- Known hypersensitivity to ST316 or any of its excipients.
- Corrected interval between Q and T wave on 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 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 (#9) listed below.
- For expansion phase only: presence of any other active malignancy requiring systemic therapy other than the disease under study.
- Concurrent anti-cancer therapy.
- Known HIV and positive -
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description ST316 & Lonsurf + Bevacizumab Combination CRC Expansion phase Lonsurf & bevacizumab ST316 \& Lonsurf \& bevacizumab n=15-30 ST316 & Fruquintinib Combination CRC Expansion phase ST316 ST316 \& Fruquintinib Combination CRC Expansion phase n=15-30 ST316 & Lonsurf + Bevacizumab Combination CRC Expansion phase ST316 ST316 \& Lonsurf \& bevacizumab n=15-30 Dose Escalation Phase ST316 The dose cohorts will be 0.5, 1, 2, 4, 8 \& 12 mg/kg IV once weekly (QW) ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase ST316 ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase n=15-30 ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase ST316 ST316 \& FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase Expansion phase n=15-30 ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase FOLFIRI regimen & bevacizumab ST316 \& FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase Expansion phase n=15-30 ST316 & Fruquintinib Combination CRC Expansion phase Fruquintinib ST316 \& Fruquintinib Combination CRC Expansion phase n=15-30
- Primary Outcome Measures
Name Time Method Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 3 years Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
- Secondary Outcome Measures
Name Time Method ST316 PK parameter AUCt 3 years Area under the concentration-time curve over the dosing interval
ST316 Assessment DOR 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
ST316 PK parameter Cmax 3 years Maximum observed serum concentration
ST316 PK parameter t1/2 3 years half life
ST316 PK parameter AUC∞ 3 years Area under the concentration-time curve over the dosing interval time from time 0 extrapolated to infinite time
ST316 PK parameter tmax. 3 years The time take to reach Maximum observed serum concentration
ST316 Assessment Overall survival (OS) 3 Years Overall survival (OS) is defined as time from first study treatment to death due to any cause.
ST316 Assessment Progression-free survival (PFS) 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.
ST316 Assessment Objective Response Rate (ORR) 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.
Trial Locations
- Locations (11)
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Westchester Medical Center
🇺🇸Valhalla, New York, United States
Fred Hutch Cancer Center
🇺🇸Seattle, Washington, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Sarah Cannon Research Institute - CO
🇺🇸Denver, Colorado, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Duke Universtiy
🇺🇸Durham, North Carolina, United States
OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Sanford Cancer Center
🇺🇸Sioux Falls, South Dakota, United States