Phase 1a/1b Study of TPST-1495 as a Single Agent and in Combination With Pembrolizumab in Subjects With Solid Tumors

Exclusion Criteria

• •1. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study, a specimen-collection study or the follow-up period of an interventional study.
• •2. Received more than 4 doses of nonsteroidal anti-inflammatory drugs or COX-2 inhibitors within 2 weeks prior to study treatment initiation.
• •3. History of allergy or hypersensitivity, GI bleed, or ulceration secondary to nonsteroidal anti-inflammatory drugs or COX-2 inhibitors.
• •4. History of GI ulcer within 1 year of treatment initiation or history of untreated helicobacter pylori infection. Subjects with history of treated helicobacter pylori infection with confirmation of eradication are eligible
• •5. History of diverticulitis or any GI bleed within 2 years of treatment initiation.
• •6. Receipt of any anticancer therapy within the following windows:
• •* Small molecule tyrosine kinase inhibitor (TKI) therapy (including investigational) within 2 weeks or 5 half-lives prior to treatment initiation, whichever is longer
• •* Any type of anti-cancer antibody or cytotoxic chemotherapy within 4 weeks prior to treatment initiation
• •* Other investigational therapy within 2 weeks or 5 half-lives prior to dosing, whichever is longer
• •7. Subjects with active or untreated central nervous system (CNS) metastases
• •8. New York Heart Association Classification II, III or IV.
• •9. Baseline QTcF \> 470 milliseconds
• •10. Receipt of live attenuated vaccines within 30 days prior to the first dose of investigational product. (Killed virus or other non-live vaccines are allowed (including most seasonal influenza vaccines, streptococcus pneumonia vaccines, and newly approved COVID-19 vaccines).
• •11. Active autoimmune disease or inflammatory disorders including inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease) requiring systemic treatment (i.e., with use of disease modifying agents, systemic corticosteroids or immunosuppressive drug) within 2 years prior to treatment initiation.
• •13. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations including a history of substance abuse that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• •14. Subjects who are receiving anti-coagulant therapy or who are considered to be at increased risk of bleeding (i.e bleeding disorder or coagulopathy).