Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC (PRESERVE-001)
Non Small Cell Lung Cancer, Advanced Solid Tumor, Metastatic Melanoma
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
. 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.
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.
- 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.
- 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.
- In Part D, patients with recurrent and/or metastatic adenoid cystic carcinoma with disease progression within 12 months are eligible.
- Patients must have RECIST V1.1 Measurable disease:
- Patient is male or female and >18 years of age on day of signing informed consent.
- Patient must have a performance status of 0 or 1 on the ECOG Performance Scale
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
- Patient has voluntarily agreed to participate by giving written informed consent.
- Female patient of childbearing potential has a negative urine or serum pregnancy test.
- 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:
- 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.
- Patients who are currently enrolled in a clinical trial of an investigational agent or device.
- Patients who are on chronic systemic steroid therapy at doses >10 mg/day
- Patients who have active symptomatic brain metastasis or leptomeningeal metastasis.
- 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.
- 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.
- Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Patients who are pregnant or breastfeeding.
- For the Part B and Part C Arm D to G, the patients that are deemed to be not suitable for Pembrolizumab.
Sites / Locations
- Highlands Oncology GroupRecruiting
- University of California at DavisRecruiting
- The Oncology Institute of Hope and InnovationRecruiting
- City of Hope Cancer CenterRecruiting
- University of Colorado HospitalRecruiting
- University of Connecticut Medical CenterRecruiting
- Nuvance HealthRecruiting
- MedStar Georgetown University HospitalRecruiting
- Florida Cancer SpecialistsRecruiting
- University of Florida Health Cancer CenterRecruiting
- Ocala Oncology Florida Cancer AffiliatesRecruiting
- AdventHealth Cancer InstituteRecruiting
- Memorial Cancer InstituteRecruiting
- Emory University Winship Cancer InstituteRecruiting
- Norton HealthRecruiting
- Greater Baltimore Medical CenterRecruiting
- The Center for Cancer and Blood DisordersRecruiting
- Dana Farber Cancer InstituteRecruiting
- Massachusetts General HospitalRecruiting
- University of Michigan Medical CenterRecruiting
- Atlantic Healthcare SystemRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- University of Cincinnati Medical CenterRecruiting
- The Ohio State University James Cancer CenterRecruiting
- Zangmeister Cancer CenterRecruiting
- Pennsylvania Cancer Specialists & Research Institute (Formerly Gettysburg Cancer Center)Recruiting
- Penn State Cancer InstituteRecruiting
- Prisma HealthRecruiting
- Tennessee Oncology Chattanooga Memorial PlazaRecruiting
- Tennessee Oncology - NashvilleRecruiting
- Houston Methodist Cancer CenterRecruiting
- Oncology ConsultantsRecruiting
- University of Utah Huntsman Cancer InstituteRecruiting
- NEXT/Virginia Cancer SpecialistsRecruiting
- University of Washington / Fred Hutchinson Cancer CenterRecruiting
- Newcastle Private HospitalRecruiting
- Tasman Oncology ResearchRecruiting
- Cancer Research SARecruiting
- Southern Oncology Clinical Research UnitRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
ONC-392 Treatment as single agent
ONC-392 in combination with pembrolizumab
The Part A study will test ONC-392 intravenous (IV) infusion up to five predefined dose levels from 0.1 mg/kg to 10 mg/kg ONC-392 as monotherapy every 21 days (Q3W). The Part A study will determine the maximal tolerable dose (MTD) and the recommended Phase 2 dose in monotherapy (RP2D-M). In Part C, Arms A-C, I-N monotherapy expansion cohorts will further assess the safety and efficacy of ONC-392 in different dose levels as monotherapy in pancreatic cancer, triple negative breast cancer, non small cell lung cancer with driver mutations, PD-1 resistant non small cell lung cancer, PD-1 resistant melanoma, head and neck cancer, ovarian cancer, renal cell carcinoma and other solid tumors. Part D is a Phase II study on recurrent and/or metastatic adenoid cystic carcinoma.
The Part B1 study will test ONC-392 intravenous (IV) infusion, Q3W, in combination with fixed dose of pembrolizumab. The dose for pembrolizumab will be fixed at 200mg/cycle dosed every 21 days (Q3W). The Part B1 will start at one level below RP2D-M dose for ONC-392 and 200mg of pembrolizumab. When 2 DLTs occur before 6 patients are enrolled, the ONC-392 dose will be decreased to the next dose level until ≤ 1/6 patients treated at that dose develops a DLT. This dose level will be designated RP2D-C. In Part C, the expansion cohorts Arm D to G will assess the safety and efficacy of ONC-392 in different dose levels and Pembrolizumab combination therapy in non small cell lung cancer, and metastatic melanoma.