Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a First-in-Human Phase IA/IB 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: OncoC4, Inc.; OncoImmune, Inc.
• Collaborator: National Cancer Institute (NCI)
• Treatments: Osimertinib; Pembrolizumab

Criteria

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 B1 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. Part B2 is for patients with non small cell lung cancer with EGFR mutations.

3. In Part C, patients with pancreatic cancer, triple negative breast cancer, non small cell lung cancer, melanoma and Merkel cell carcinoma are eligible.

4. Measurable disease:

i. In Phase IA dose-finding studies (trial A and B), patients may have non-measurable disease.

ii. In Phase IB expansion cohorts, patients must have measurable disease as defined per RECIST version 1.1: iii. Tumor mass: Must be accurately measurable in at least 1 dimension (longest diameter to be recorded) with a minimum size of:

1. 10 mm by computed tomography (CT) scan (CT scan slide thickness must be <5 mm),

2. 20 mm by chest X-ray (if clearly defined and surrounded by aerated lung). iv. Malignant lymph nodes: >15 mm in short axis when assessed by CT scan (CT scan slice thickness must be <5 mm).

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 ≤ 2 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. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.

7. Female patients enrolled in the study, who are not free from menses for >2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use 2 adequate barrier methods of contraception to prevent pregnancy or to abstain from heterosexual activity throughout the study, starting with Visit 1 through 30 days after the last dose of study therapy. Approved contraceptive methods include for example; intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.

8. Male patients must agree to use an adequate method 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 previously had a severe hypersensitivity reaction to another mAb.

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 B1 and Part C Arm D to H, the patients that are deemed to be not suitable for Pembrolizumab.