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

Inclusion Criteria:

1. Able and willing to sign an informed consent form (ICF) and comply with the protocoland 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:

5. For the dose-escalation phase: CRC, HCC, TNBC, NSCLC, OC, melanoma, CCA, andSS.

6. For the expansion phase: CRC. Note: if additional indications and combinationsare added inclusion/exclusion criteria will be updated.

7. Agrees to provide a newly obtained biopsy of an accessible lesion (if they can bebiopsied based on the Investigator's assessment) prior to the start of studytreatment, and to repeat biopsy once during study treatment. Tissue obtained for thebiopsy must not be previously irradiated, but a new or progressing lesion in theradiation field is acceptable. Subjects without accessible lesion for biopsy must beable to provide an archival tumor tissue sample for central lab analysis.

8. In the Investigator's opinion, the subject may not derive clinical benefit from, oris ineligible for, a particular form of standard therapy on medical grounds, or thesubject failed or did not tolerate one or more of other anticancer therapies: a. For the dose escalation phase: i. Refractory, intolerant, or refused availablestandard-of-care therapies. ii. Up to three previous lines of systemic anticancertherapies for metastatic disease are allowed (adjuvant or neoadjuvant setting do notcount 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 theexpansion.

3. Corrected interval between Q and T wave on electrocardiogram (ECG) (QTc) > 480 msecusing Fredericia's formula.

4. Symptomatic ascites or pleural effusion. A subject who is clinically stable for 4weeks following treatment for these conditions (including therapeutic thoraco- orparacentesis) is eligible.

5. Known active central nervous system (CNS) metastases and/or carcinomatousmeningitis. Subjects with previously treated brain metastases may participateprovided they are clinically stable for at least 2 weeks prior to study entry andhave no evidence of new or enlarging brain metastases. Subjects with treated brainmetastases must also follow the steroid exclusion criterion (#11) listed below.

6. For expansion phase only: presence of any other active malignancy requiring systemictherapy other than the disease under study.

7. For subjects to be treated with a regimen containing bevacizumab:

8. History of cardiac disease: congestive heart failure (CHF) ≥NYHA Class II;active coronary artery disease, myocardial infarction within 6 months prior tostudy entry; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring anti-arrhythmictherapy (βeta blockers or digoxin are permitted).

9. Current uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg ordiastolic pressure >90 mmHg despite optimal medical management) as well asprior history of hypertensive crisis or hypertensive encephalopathy.

10. History of arterial thrombotic or embolic events (within 6 months prior tostudy entry).

11. Significant vascular disease (e.g., aortic aneurysm, aortic dissection,symptomatic peripheral vascular disease).

12. Evidence of bleeding diathesis or clinically significant coagulopathy.

13. Major surgical procedure (including open biopsy, significant traumatic injury,etc.) within 28 days, or anticipation of the need for major surgical procedureduring the course of the study as well as minor surgical procedure (excludingplacement of a vascular access device or bone marrow biopsy) within 7 daysprior to study enrollment.

14. Proteinuria at screening as demonstrated by urinalysis with proteinuria ≥2+ (subjects discovered to have ≥2+ proteinuria on dipstick urinalysis at baselineshould undergo a 24-hour urine collection and must demonstrate ≤1g of proteinin 24 hours to be eligible).

15. History of abdominal fistula, gastrointestinal perforation, peptic ulcer, orintraabdominal abscess within 6 months.

16. Ongoing serious, non-healing wound, ulcer, or bone fracture.

17. History of reversible posterior leukoencephalopathy syndrome (RPLS).

18. History of hypersensitivity to Chinese hamster ovary (CHO) cells or other humanor humanized recombinant antibodies.