Colon Cancer, Metastatic Colon Cancer
Conditions
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.
Interventions
DRUGST316
IV
DRUGFOLFIRI 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.
DRUGFruquintinib
5 mg once a day for the first 21 days of a 28-day cycle
DRUGLonsurf & 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
Sponsors
Sapience Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
STUDY_CHAIRAbi Vainstein-Haras
CMO
Outcome results
None listed