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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05848739
• Other study ID #: ST316-101
• Status: Recruiting
• Phase: Phase 1
• Start date: June 5, 2023
• Est. completion date: May 31, 2027

Study information

• Verified date: June 2024
• Source: Sapience Therapeutics
• Contact: Steve Kaesshaefer
• Phone: 9737152917
• Email: steve.kaesshaefer[@]bexonclinical.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 115
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Able and willing to sign ICF and comply with the protocol and the restrictions and assessments therein.

2. Male or female =18 years of age.

3. ECOG performance status 0-1.

4. Must have a locally advanced or metastatic inoperable tumor as follows:

1. For the dose escalation/regimen exploration phase: CRC, BC, NSCLC, OC, pancreatic adenocarcinoma, melanoma, CC, and synovial sarcoma.

2. For the expansion phase: CRC

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.

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.

Exclusion Criteria:

1. Known hypersensitivity to ST316 or any of its excipients.

2. Corrected interval between Q and T wave on ECG (QTc) > 480 msec using Fredericia's formula.

3. 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.

4. 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.

5. For expansion phase only: presence of any other active malignancy requiring systemic therapy other than the disease under study.

6. Concurrent anti-cancer therapy.

7. Known HIV and positive -

Related Conditions & MeSH terms

• Breast Cancer Metastatic
• Breast Neoplasms
• Cholangiocarcinoma
• Colon Cancer
• Colonic Neoplasms
• Hepatocellular Carcinoma
• Melanoma
• Melanoma Recurrent
• Melanoma Stage IV
• Metastatic Colon Cancer
• Metastatic Melanoma
• Metastatic Skin Cancer
• NSCLC, Metastatic
• Ovarian Cancer
• Pancreatic Cancer
• Sarcoma, Synovial
• Synovial Sarcoma
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• ST316
IV
• 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.
• Fruquintinib
5 mg once a day for the first 21 days of a 28-day cycle

Locations

Country	Name	City	State
United States	Sarah Cannon Research Institute - CO	Denver	Colorado
United States	Duke Universtiy	Durham	North Carolina
United States	START Midwest	Grand Rapids	Michigan
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Sanford Cancer Center	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Sapience Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	3 years
Secondary	ST316 PK parameter AUCt	Area under the concentration-time curve over the dosing interval	3 years
Secondary	ST316 Assessment DOR	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
Secondary	ST316 PK parameter Cmax	Maximum observed serum concentration	3 years
Secondary	ST316 PK parameter t1/2	half life	3 years
Secondary	ST316 PK parameter AUC8	Area under the concentration-time curve over the dosing interval time from time 0 extrapolated to infinite time	3 years
Secondary	ST316 PK parameter tmax.	The time take to reach Maximum observed serum concentration	3 years
Secondary	ST316 Assessment Overall survival (OS)	Overall survival (OS) is defined as time from first study treatment to death due to any cause.	3 Years
Secondary	ST316 Assessment Progression-free survival (PFS)	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
Secondary	ST316 Assessment Objective Response Rate (ORR)	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