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

Overview

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

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.

   1. 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 -