Safety, Pharmacokinetics (PK), and Efficacy of ONC-392 as a Single Agent and in Combination with Pembrolizumab in Advanced Solid Tumors and NSCLC: An Open-label Phase IA/IB/II Study (PRESERVE-001)

This is a First-in-Human Phase IA/IB/II open label dose escalation study of intravenous (IV)
administration of ONC-392, a humanized anti-CTLA4 IgG1 monoclonal antibody, as single agent
and in combination with pembrolizumab in participants with advanced or metastatic solid
tumors and non-small cell lung cancers.

Inclusion Criteria:

1. . Patients must have a histological or cytological diagnosis of NSCLC or any other
type of carcinoma or sarcomas, progressive metastatic disease, or progressive locally
advanced disease not amenable to local therapy.

1. In the Part A Phase I dose escalation study of ONC-392 monotherapy, patients with
advanced/metastatic solid tumors of any histology are eligible for participation.

Please note: tumor types of primary interest in this study are malignant
melanoma, renal cell carcinoma, hepatocellular carcinoma, non-small cell lung
cancer, head and neck carcinoma, gastric carcinoma, ovarian carcinoma, colorectal
cancer, any type of sarcoma.

2. In Part B dose finding of the ONC-392 plus pembrolizumab combination, patients
with advanced/metastatic solid tumors of any histology that Pembrolizumab has
been approval as standard of care are eligible for participation.

3. In Part C, patients with pancreatic cancer, triple negative breast cancer, non
small cell lung cancer, melanoma, Head and Neck cancer, ovarian cancer, and other
solid tumors are eligible.

4. In Part D, patients with recurrent and/or metastatic adenoid cystic carcinoma
with disease progression within 12 months are eligible.

5. Patients must have RECIST V1.1 Measurable disease:

2. Patient is male or female and >18 years of age on day of signing informed consent.

3. Patient must have a performance status of 0 or 1 on the ECOG Performance Scale

4. Patient must have adequate organ function as indicated by the following laboratory
values:

Hematological: Absolute neutrophil count (ANC) ≥1,500 /mcL; Plateletsa ≥100,000 / mcL;
Hemoglobin ≥9 g/dL or ≥5.6 mmol/L- without qualifications; Renal: Serum creatinine
≤1.5 X upper limit of normal (ULN); Hepatic: Serum total bilirubin ≤1.5 X ULN; OR
Direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 ULN; AST (SGOT)
and ALT (SGPT) ≤2.5 X ULN, OR ≤5 X ULN for patients with active liver metastases
Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN
Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN

5. Patient has voluntarily agreed to participate by giving written informed consent.

6. Female patient of childbearing potential has a negative urine or serum pregnancy test.

7. Female and Male patients must agree to use adequate methods of contraception starting
with the first dose of study drug through 90 days after the last dose of study
therapy.

Exclusion Criteria:

A patient meeting any of the following criteria is not eligible to participate in this
study:

1. Patients who have not recovered to CTCAE ≤ 1 from the AE due to cancer therapeutics.
The washout period for cancer therapeutic drugs (such as chemotherapy, radioactive, or
targeted therapy) is 21 days, and for antibody drug 28 days.

2. Patients who are currently enrolled in a clinical trial of an investigational agent or
device.

3. Patients who are on chronic systemic steroid therapy at doses >10 mg/day

4. Patients who have active symptomatic brain metastasis or leptomeningeal metastasis.

5. Patients who have an active infection requiring systemic IV therapy within 14 days of
prior to administration of ONC-392 or combined ONC-392 and Pembrolizumab.

6. Patients who have a history or current evidence of any condition, therapy, or
laboratory abnormality that might confound the results of the study, interfere with
the patient's participation for the full duration of the study, or is not in the best
interest of the patient to participate, in the opinion of the treating Investigator.

7. Patients with known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

8. Patients who are pregnant or breastfeeding.

9. For the Part B and Part C Arm D to G, the patients that are deemed to be not suitable
for Pembrolizumab.