A Phase 1-2 Dose-escalation and Expansion Study of ST316 in Subjects With Selected Advanced Unresectable and Metastatic Solid Tumors
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.
• Able and willing to sign an informed consent form (ICF) and comply with the protocol and the restrictions and assessments therein.
• Male or female ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Must have a locally advanced or metastatic inoperable tumor as follows:
‣ For the dose-escalation phase: CRC, HCC, TNBC, NSCLC, OC, melanoma, CCA, and SS.
⁃ For the expansion phase: CRC. Note: if additional indications and combinations are added inclusion/exclusion criteria will be updated.
• 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.
• 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.