Clinical trial NCT05848739: A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors
Official title: A Phase 1-2 Dose-escalation and Expansion Study of ST316 in Subjects With Selected Advanced Unresectable and Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Colon Cancer
Metastatic Colon Cancer
Lead sponsor: Sapience Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-05-08
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: 3 years
Secondary outcomes:
measure: ST316 PK parameter AUCt
timeFrame: 3 years
measure: ST316 Assessment DOR
timeFrame: 3 years
measure: ST316 PK parameter Cmax
timeFrame: 3 years
measure: ST316 PK parameter t1/2
timeFrame: 3 years
measure: ST316 PK parameter AUC∞
timeFrame: 3 years
measure: ST316 PK parameter tmax.
timeFrame: 3 years
measure: ST316 Assessment Overall survival (OS)
timeFrame: 3 Years
measure: ST316 Assessment Progression-free survival (PFS)
timeFrame: 3 Years
measure: ST316 Assessment Objective Response Rate (ORR)
timeFrame: 3 Years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute - CO
state: Colorado
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Durham
country: United States
facility: Duke Universtiy
state: North Carolina
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
city: Seattle
country: United States
facility: Fred Hutch Cancer Center
state: Washington
Study officials:
affiliation: CMO
name: Abi Vainstein-Haras
role: STUDY_CHAIR
References: