Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067

Eligibility Criteria

• 1. Male and female patients aged ≥18 years
• 2. Must provide written informed consent and any authorizations required by local law
• 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• 4. Have histologically or cytologically confirmed diagnosis of advanced/metastatic solid tumor
• 1. For patients who have developed disease progression through standard therapy, or
• 2. For patients whom standard of care therapy that prolongs survival is unavailable or unsuitable (according to the investigator and after consultation with the Medical Monitor) For Phase 1 combination therapy dose escalation, the following solid tumors are allowed: Melanoma, Merkel cell, RCC, urothelial, NSCLC (with no EGFR, TRK receptor, or ALK positive mutations/fusions), TNBC, SCCHN, MSI-Hi tumors, Hi TMB or mismatch repair deficient, gastric, cervical, endometrial, cutaneous squamous, small cell lung, esophageal, and HCC
• * TNBC is diagnosed in a tumor which does not express estrogen receptor or progesterone receptor, is not human epidermal growth factor receptor 2 (HER2) 3+ on IHC or is negative by fluorescence in situ hybridization (FISH).
• * MSI high tumor should have mutations in 30% or more microsatellites by PCR or be negative for MSH1/2/6 or PMS-2 by IHC.
• * Hi-TMB high tumor has 10 mut/Mb or greater calculated from whole genome sequencing or whole exome sequencing
• 5. Has at least 1 measurable lesion per RECIST 1.1 criteria which has not been biopsied or received prior irradiation
• 6. Has an accessible tumor for biopsy pre- and on-treatment (mandatory).
• 1. History of another malignancy
• 2. Known symptomatic brain metastases requiring \>10 mg/day of prednisolone or equivalent
• 3. Significant cardiovascular disease (MI, thrombotic events,) within 6 months prior to study treatmentSignificant ECG abnormalities (Phase 1a and 2 monotherapy only) including unstable cardiac arrhythmia requiring medication, second-degree atrioventricular block type II, third degree AV
• 4. Any degree of respiratory compromise (from either malignant or non-malignant disease)
• 5. Evidence of an ongoing systemic bacterial, fungal, or viral infection
• 6. Has received a live vaccine within 30 days
• 7. Major surgery within 4 weeks
• 8. Prior solid organ or bone marrow progenitor cell transplantation
• 9. Prior high dose chemotherapy requiring stem cell rescue
• 10. History of active autoimmune disorders
• 11. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids.
• 12. Treatment with an approved, systemic anticancer therapy or an investigational agent within 4 weeks of Day 1
• 13. A positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral test within 28 days prior to dosing, unless there is Investigator-confirmed clinical recovery on or before C1D1
• 14. Subjects with adrenal insufficiency
• 15. Subjects with any chemistry or hematology laboratory values that are ≥Grade 2
• 16. Presence of known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• 17. Prior radiotherapy within 2 weeks of start of study treatment or history of radiation pneumonitis.
• 18. Presence of an active documented autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine or insulin) is not considered a form of systemic treatment and is allowed. Subjects may use topical and/or inhaled corticosteroids. However, subjects with adrenal insufficiency on replacement doses of steroids are not allowed.
• 19. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137), and was discontinued from that treatment due to a Grade 3 or higher irAE
• 20. Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. Subjects who have been retreated after such a reaction may be allowed after discussion with the Simcha Medical Monitor
• 21. History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• 22. Subjects that have received radiation therapy to the lung that is \>30Gy within 6 months of the first dose of study treatment