PTT-936 Alone or in Combination in Patients With Locally Advanced or Metastatic Solid Tumors

Inclusion Criteria:

1. Voluntarily signed informed consent form (ICF).

2. Ability and willingness to adhere to all study procedures.

3. Male or female patients ≥ 18 years of age at the time of signing the ICF.

4. Locally advanced unresectable or metastatic solid tumor confirmed by histology orcytology

5. For Part A: On tumor imaging, as assessed by RECIST v1.1 and iRECIST, withmeasurable or unmeasurable disease. For Part B: On tumor imaging, as assessed byRECIST v1.1 and iRECIST, with at least one measurable disease.

6. Life expectancy ≥ 3 months.

7. Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1 for Part Aand Part B.

8. Adequate end-organ and hematopoietic function, defined based on the followinglaboratory results obtained within 7 days prior to the first dose of study treatment [Day 1]):

9. Absolute neutrophil count (ANC) ≥ 1.5×109/L (1500/μL), without granulocytecolony-stimulating factor (G-CSF) support. Note that G-CSF may be administereduntil 14 days prior to Cycle 1 Day 1 (C1D1).

10. Platelet count ≥ 90×109/L (90,000/μL) without transfusion within 14 days priorto C1D1.

11. Hemoglobin ≥ 90 g/L (9 g/dL). Note that patients may be transfused or receiveerythropoietic treatment to meet this criterion until 14 days prior to C1D1.

12. Creatinine clearance ≥ 60 mL/min.

13. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x theupper limit of normal (ULN) with or without primary or metastatic liver tumorlesions.

14. Total bilirubin (TBIL) ≤ 1.5 x ULN.

15. For patients not receiving therapeutic anticoagulation: InternationalNormalized Ratio (INR), activated partial thromboplastin time (aPTT) andprothrombin time (PT) ≤ 1.5 x ULN.

16. For patients receiving warfarin: INR ≤ 3.0 x ULN and no bleeding within 14 daysprior to Day 1. Patients receiving therapeutic anticoagulation must be on astable dose for a minimum of 14 days prior to Day 1. Patients on low molecularweight heparin will be allowed.

Exclusion Criteria:

1. Patients with leptomeningeal (LMD) metastases or patients with new and/orprogressive brain metastases at the time of study entry. Patients with treated brainmetastases are eligible if there is no evidence of progression for at least 4 weeksafter central nervous system (CNS)-directed treatment (radiotherapy and/or surgery),as ascertained by clinical examination and brain imaging (MRI or CT) during thescreening period.

2. History of primary malignancy other than the diseases under study, not in remissiongreater than three (3) years prior to Day 1. Exceptions that do not require a 3-yearremission include: adequately treated non-melanoma skin cancer, cervical carcinomain situ on biopsy or squamous intraepithelial lesion on Papanicolaou (PAP) smear, insitu prostate cancer (with no evidence of active disease for two [2] years prior toDay 1), or resected melanoma in situ and radically resected papillary thyroidcarcinoma.

3. Persistence of Adverse Events (AEs) from prior anti-cancer therapy that have notresolved to Grade 1 (except for alopecia and hypothyroidism), or any history ofGrade ≥ 3 immune-related adverse events (irAEs), Grade ≥ 2 pneumonitis, hypophysitisor encephalitis related to immunotherapy, or other Grade ≥ 3 drug-related CNStoxicity.

4. Active systemic autoimmune disease or a history of autoimmune disorder that mayrelapse (e.g., systemic lupus erythematosus [SLE], rheumatoid arthritis,inflammatory bowel disease [IBD], autoimmune thyroid disorder*, multiple sclerosis,vasculitis, glomerulitis, eczema, psoriasis, etc.).

*Note that primary or secondary hypothyroidism, well controlled with hormonereplacement therapy is permitted.

5. Major trauma or major surgery within 4 weeks prior to Day 1 or anticipated majorsurgery during study participation.

6. Serious unhealing wound, ulcer, or bone fracture.

7. History of and/or presence of any of the following cardiovascular andcerebrovascular events or conditions:

8. History of myocardial infarction, unstable or severe angina, or arterialthrombotic event (such as cerebrovascular attack [CVA] or transient ischemicattack [TIA]) within 12 months prior to Day 1.

9. Significant abnormalities on the screening of ECG, including corrected QTinterval (QTc interval) > 470 msec (average of triplicate measurements,corrected for heart rate using Fridericia's formula), second degree (Mobitztype II) or third degree atrioventricular (AV) block, or other clinicallysignificant (in the Investigator's opinion) arrhythmia.

10. Current New York Heart Association (NYHA) stage II-IV congestive heart failure (CHF).

11. Left ventricular ejection fraction (LVEF) < 50%. • Note that LVEF assessment by echocardiogram (ECHO) scan performed as part ofthe patient's regular care within 4 weeks prior to the screening visit may beused for confirmation of eligibility.

12. Other clinically significant (in the Investigator's opinion) cardiac diseases (e.g., valvular disease, cardiomegaly, ventricular hypertrophy, cardiomyopathy,myocarditis, etc.).

13. Uncontrolled hypertension (defined as a systolic blood pressure [SBP] ≥ 150mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg at screening), despiteappropriate antihypertensive therapy, or poor compliance with anantihypertensive regimen.

14. Active or recent (past 6 months) bleeding disorder, including gastrointestinal (GI)bleeding, as evidenced by hematemesis, significant hemoptysis, or melena within 6months prior to Day 1.

15. Uncontrolled diabetes.

16. Chronic severe liver disease or Child-Pugh B or C liver cirrhosis.

17. History of alcoholism or drug abuse within the past year.