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Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC (PRESERVE-001)

Primary Purpose

Non Small Cell Lung Cancer, Advanced Solid Tumor, Metastatic Melanoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ONC-392
Pembrolizumab
Sponsored by
OncoC4, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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

Arm Type

Experimental

Experimental

Arm Label

ONC-392 Treatment as single agent

ONC-392 in combination with pembrolizumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Dose limiting toxicity (DLT) in monotherapy
The number of subjects who have dose limiting toxicity during the first cycle of study drug, ONC-392, administration.
Maximal tolerable dose (MTD) in monotherapy
The study drug, ONC-392, dose level that has two out of six subjects who have dose limiting toxicity.
Recommended Phase II Dose (RP2D)
The study drug, ONC-392, dose level that is one level below MTD, or an intermediate dose level that below MTD and pre-specified in protocol. This dose level will be the RP2D for monotherapy.
Rate of treatment related adverse events (TRAE) according to CTCAE v5.0
The safety profile will be presented as tabulated TRAE.

Secondary Outcome Measures

The serum half life of the study drug, ONC-392, in monotherapy.
To determine the drug concentration in serum samples that are taken in various timepoints during the treatment in order to calculate drug half life.
The serum half life of the study drug, ONC-392, in combination therapy with Pembrolizumab.
To determine the drug concentration in serum samples that are taken in various timepoints during the treatment in order to calculate drug half life.
Objective Response Rate (ORR)
To determine the objective response rate based on RECIST v1.1.
Progression Free Survival (PFS)
To determine the progression free survival based on RECIST 1.1 and iRECIST.
Overall Survival (OS)
To determine the overall survival.

Full Information

First Posted
October 24, 2019
Last Updated
March 16, 2023
Sponsor
OncoC4, Inc.
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04140526
Brief Title
Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC
Acronym
PRESERVE-001
Official Title
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 Study. Preserve CTLA4 Checkpoint Function (PRESERVE-001)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 16, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OncoC4, Inc.
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), also known as CD152 (cluster of differentiation 152), is a cell surface protein receptor that interacts with B7-1 (CD80) and B7-2 (CD86) to ensure proper function of regulatory T cells and protect host against autoinflammatory diseases. Anti-CTLA-4 monoclonal antibodies (mAbs) have demonstrated strong and broad cancer immunotherapeutic effects (CITE) in a variety of preclinical models and are used clinically both as monotherapy and as part of combination therapy with Nivolumab (anti-PD-1). However, CTLA-4 monotherapy has more immunotherapy-related adverse effects (irAEs) than anti-PD-1/PD-L1 therapy. In addition, the rate of severe irAE (Grades 3 and 4) reached 55% in melanoma patients receiving combination of Ipilimumab and Nivolumab. The strong irAEs further limit the doses tolerated by cancer patients. Nevertheless, combination with anti-PD-1 resulted in significantly improved response rates and patient survival in multiple types of cancer. Furthermore, anti-CTLA-4 antibodies induce long-lasting immunity in cancer patients. Therefore, CTLA-4 remains an important immunotherapy target, but major challenges remain in improving both safety and efficacy of anti-CTLA-4 mAbs. ONC-392 is a highly selective, humanized monoclonal IgG1-kappa isotype antibody against CTLA-4. The parental clone was identified through in vivo screening in humanized CTLA-4 mouse model for high anti-tumor efficacy and low autoimmune toxicity. We have recently demonstrated that ONC-392 is dissociation from CTLA-4 under low pH to allow its escape from lysosomal degradation and recycle to cell surface. We have provided several lines of evidence for the notion that a pH-sensitive antibody ONC-392 is not only safer but also more effective in Treg depletion and tumor rejection than the Ipilimumab, which is pH-insensitive. First, by preserving CTLA-4 on the cell surface, Onc-392 leaves higher ligand density for better ADCC. Second, Onc-392 is more efficient in Treg depletion in tumor microenvironment. Third, Onc-392 is significantly more potent in inducing rejection of large tumors. The study consists of four parts: (1) The Part A study is a dose-finding rapid titration, Phase I trial of ONC-392 as a single agent in patients with advanced or metastatic solid tumors with various histology. The aim of this trial is to define the recommended Phase II dose for ONC-392 monotherapy (RP2D-M). (2) The Part B study is a dose-finding phase with ONC-392 in combination with a standard dose of 200 mg pembrolizumab in patients with advanced or metastatic solid tumors. (3) The Part C consists of different expansion arms. Arm A: Pancreatic Cancer Cohort, ONC-392 monotherapy, will enroll advanced/metastatic pancreatic cancer patients who have progressive disease after first and second lines of systemic treatment. Arm B: TNBC Cohort, ONC-392 monotherapy, will enroll advanced/metastatic TNBC patients who have progressive disease after prior systemic treatments, including checkpoint inhibitor immunotherapy. Arm C: NSCLC Mono Cohort 1, ONC-392 monotherapy, will enroll advanced/metastatic NSCLC patients with EGFR or ALK mutations who have progressive disease after prior systemic treatments, including targeted therapy or checkpoint inhibitors. Arm D: NSCLC IO Naïve Cohort, ONC-392/Pembrolizumab combination therapy, will enroll advanced/metastatic NSCLC cancer patients who are treatment naïve, or anti PD (L)1 immunotherapy naïve and PD-L1-positive (PD L1 TPS ≥ 1%). Arm E: NSCLC IO R/R Cohort, ONC-392/Pembrolizumab combination therapy, will enroll advanced/metastatic NSCLC cancer patients who are R/R to prior anti-PD-(L)1 immunotherapy regardless of PD-L1 status. Arm F: Melanoma IO Naïve Cohort, ONC-392/Pembrolizumab combination therapy, will enroll advanced/metastatic Melanoma patients who are treatment naïve, or checkpoint inhibitor immunotherapy naive. Prior systemic chemotherapy or targeted therapy are allowed. Arm G: Melanoma IO R/R Cohort, ONC-392/Pembrolizumab combination therapy, will enroll advanced/metastatic melanoma patients who are R/R to anti-PD-(L)1 immunotherapy. Arm I: NSCLC Mono Cohort 2, ONC-392 monotherapy, will enroll advanced/metastatic NSCLC patients without EGFR or ALK mutations who have progressive disease after prior systemic treatments, including chemotherapy or checkpoint inhibitors. Patient must have anti-PD-(L)1 treatment, either alone or in combination, as last treatment before enrollment. Prior anti-CTLA-4 treatment is allowed. Arm J: Melanoma Mono Cohort, ONC-392 monotherapy, will enroll advanced/metastatic melanoma patients who are R/R to anti-PD-(L)1 immunotherapy. Arm K: Head and Neck Squamous Cell Carcinoma (HNSCC), ONC-392 monotherapy, will enroll advanced/metastatic HNSCC patients with or without positive HPV who have progressive disease after prior systemic treatments, including chemotherapy or checkpoint inhibitors. Patient must have anti-PD-(L)1 treatment, either alone or in combination, as last treatment before enrollment. Arm L: Ovarian Cancer, ONC-392 monotherapy, will enroll patients with advanced/metastatic ovarian cancer who have progressive disease after prior systemic treatments, including chemotherapy, targeted therapy or checkpoint inhibitors. Arm M: Solid Tumors, ONC-392 monotherapy, will enroll patients with advanced/metastatic solid tumors who are not eligible for Arm A-C or H-L, who have progressive disease after prior systemic treatments, including chemotherapy, targeted therapy or checkpoint inhibitors. Arm N: Renal Cell Carcinoma, ONC-392 monotherapy, will enroll advanced/metastatic RCC patients who are R/R to anti-PD-(L)1 immunotherapy. (4) Part D is a Phase II study in recurrent and/or metastatic adenoid cystic carcinoma with ONC-392 monotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer, Advanced Solid Tumor, Metastatic Melanoma, Metastatic Head and Neck Carcinoma, Metastatic Renal Cell Carcinoma, Metastatic Colorectal Cancer, Sarcomas, Metastatic Prostate Cancer, Ovarian Cancer, Small Cell Lung Cancer, Metastatic Breast Cancer, Pancreas Cancer, Gastric Cancer, Esophageal Cancer, Gastroesophageal Junction Adenocarcinoma, Cervical Cancer, Adenoid Cystic Carcinoma, Salivary Gland Cancer, Urothelial Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Open label
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
914 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ONC-392 Treatment as single agent
Arm Type
Experimental
Arm Description
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.
Arm Title
ONC-392 in combination with pembrolizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ONC-392
Other Intervention Name(s)
A humanized anti-CTLA4 IgG1 monoclonal antibody made by OncoC4, Inc.
Intervention Description
ONC-392 will be given by intravenous infusion, once every 21 days (Q3W). In Part C Arm M and in Part D, ONC-392 will be given Q4W.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, MK3475
Intervention Description
Pembrolizumab will be given intravenous (IV) infusion at 200 mg/cycle, once every 21 days (Q3W).
Primary Outcome Measure Information:
Title
Dose limiting toxicity (DLT) in monotherapy
Description
The number of subjects who have dose limiting toxicity during the first cycle of study drug, ONC-392, administration.
Time Frame
21 days
Title
Maximal tolerable dose (MTD) in monotherapy
Description
The study drug, ONC-392, dose level that has two out of six subjects who have dose limiting toxicity.
Time Frame
21 days
Title
Recommended Phase II Dose (RP2D)
Description
The study drug, ONC-392, dose level that is one level below MTD, or an intermediate dose level that below MTD and pre-specified in protocol. This dose level will be the RP2D for monotherapy.
Time Frame
21 days
Title
Rate of treatment related adverse events (TRAE) according to CTCAE v5.0
Description
The safety profile will be presented as tabulated TRAE.
Time Frame
One year
Secondary Outcome Measure Information:
Title
The serum half life of the study drug, ONC-392, in monotherapy.
Description
To determine the drug concentration in serum samples that are taken in various timepoints during the treatment in order to calculate drug half life.
Time Frame
12 weeks
Title
The serum half life of the study drug, ONC-392, in combination therapy with Pembrolizumab.
Description
To determine the drug concentration in serum samples that are taken in various timepoints during the treatment in order to calculate drug half life.
Time Frame
12 weeks
Title
Objective Response Rate (ORR)
Description
To determine the objective response rate based on RECIST v1.1.
Time Frame
1 year
Title
Progression Free Survival (PFS)
Description
To determine the progression free survival based on RECIST 1.1 and iRECIST.
Time Frame
1 year
Title
Overall Survival (OS)
Description
To determine the overall survival.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pan Zheng, MD, PhD
Phone
202 751 6823
Email
pzheng@oncoc4.com
First Name & Middle Initial & Last Name or Official Title & Degree
Martin Devenport, PhD
Phone
4102070582
Email
mdevenport@oncoc4.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tianhong Li, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
Highlands Oncology Group
City
Springdale
State/Province
Arkansas
ZIP/Postal Code
72762
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Schaefer
Facility Name
University of California at Davis
City
Davis
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tianhong Li, MD, PhD
Facility Name
The Oncology Institute of Hope and Innovation
City
Downey
State/Province
California
ZIP/Postal Code
90241
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richy Agajanian, MD
Facility Name
City of Hope Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lorna Rodriguez, MD
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Bowles, MD
Facility Name
University of Connecticut Medical Center
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Tannenbaum, MD
Facility Name
Nuvance Health
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06856
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Frank, MD
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aiwu He, MD, PhD
Facility Name
Florida Cancer Specialists
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shaachi Gupta, MD
Facility Name
University of Florida Health Cancer Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas George, MD
Facility Name
Ocala Oncology Florida Cancer Affiliates
City
Ocala
State/Province
Florida
ZIP/Postal Code
34474
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rama Balaraman, MD
Facility Name
AdventHealth Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Socinski, MD
Facility Name
Memorial Cancer Institute
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adriana Milillo-Naraine, MD
Facility Name
Emory University Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicole C Schmitt, MD
First Name & Middle Initial & Last Name & Degree
Nabil F Saba, MD
Facility Name
Norton Health
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Hamm, MD
Facility Name
Greater Baltimore Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mei Tang, MD, PhD
Facility Name
The Center for Cancer and Blood Disorders
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Goldstein, MD
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Glenn Hanna, MD
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Colin Weekes, MD
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ulka Vaishampayan, MD
Facility Name
Atlantic Healthcare System
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Whitman, MD
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenneth Yu, MD
First Name & Middle Initial & Last Name & Degree
Eileen O'Reilly, MD
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Jackson, MD
Facility Name
The Ohio State University James Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kai He, MD, PhD
Facility Name
Zangmeister Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sameh Mikhail, MD
Facility Name
Pennsylvania Cancer Specialists & Research Institute (Formerly Gettysburg Cancer Center)
City
Gettysburg
State/Province
Pennsylvania
ZIP/Postal Code
17325
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Satish Shah, MD
Facility Name
Penn State Cancer Institute
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Ma, MD
Facility Name
Prisma Health
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ki Young Chung, MD
Facility Name
Tennessee Oncology Chattanooga Memorial Plaza
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edward Arrowsmith, MD
Facility Name
Tennessee Oncology - Nashville
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meredith McKean, MD
Facility Name
Houston Methodist Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jenny Chang, MD
Facility Name
Oncology Consultants
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julio Peguero, MD
Facility Name
University of Utah Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Siwen Hu-Lieskovan, MD, PhD
Facility Name
NEXT/Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Spira, MD
Facility Name
University of Washington / Fred Hutchinson Cancer Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cristina P Rodriguez, MD
Facility Name
Newcastle Private Hospital
City
New Lambton Heights
State/Province
New South Wales
ZIP/Postal Code
2305
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hiren Mandaliya, MD
Facility Name
Tasman Oncology Research
City
Southport
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Hill, MD
Facility Name
Cancer Research SA
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rohit Joshi, MD
Facility Name
Southern Oncology Clinical Research Unit
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ganessan Kitchenadasse, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31267017
Citation
Zhang Y, Du X, Liu M, Tang F, Zhang P, Ai C, Fields JK, Sundberg EJ, Latinovic OS, Devenport M, Zheng P, Liu Y. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Res. 2019 Aug;29(8):609-627. doi: 10.1038/s41422-019-0184-1. Epub 2019 Jul 2.
Results Reference
background
PubMed Identifier
29472691
Citation
Du X, Tang F, Liu M, Su J, Zhang Y, Wu W, Devenport M, Lazarski CA, Zhang P, Wang X, Ye P, Wang C, Hwang E, Zhu T, Xu T, Zheng P, Liu Y. A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Cell Res. 2018 Apr;28(4):416-432. doi: 10.1038/s41422-018-0011-0. Epub 2018 Feb 22.
Results Reference
background
PubMed Identifier
29463898
Citation
Du X, Liu M, Su J, Zhang P, Tang F, Ye P, Devenport M, Wang X, Zhang Y, Liu Y, Zheng P. Uncoupling therapeutic from immunotherapy-related adverse effects for safer and effective anti-CTLA-4 antibodies in CTLA4 humanized mice. Cell Res. 2018 Apr;28(4):433-447. doi: 10.1038/s41422-018-0012-z. Epub 2018 Feb 20.
Results Reference
background
PubMed Identifier
15486062
Citation
May KF Jr, Roychowdhury S, Bhatt D, Kocak E, Bai XF, Liu JQ, Ferketich AK, Martin EW Jr, Caligiuri MA, Zheng P, Liu Y. Anti-human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a hu-PBL-SCID model: a new method for preclinical screening of costimulatory monoclonal antibodies. Blood. 2005 Feb 1;105(3):1114-20. doi: 10.1182/blood-2004-07-2561. Epub 2004 Oct 14.
Results Reference
background
PubMed Identifier
16037385
Citation
Lute KD, May KF Jr, Lu P, Zhang H, Kocak E, Mosinger B, Wolford C, Phillips G, Caligiuri MA, Zheng P, Liu Y. Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti-CTLA-4 antibodies. Blood. 2005 Nov 1;106(9):3127-33. doi: 10.1182/blood-2005-06-2298. Epub 2005 Jul 21.
Results Reference
background
PubMed Identifier
31836191
Citation
Liu Y, Zheng P. Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy. Trends Pharmacol Sci. 2020 Jan;41(1):4-12. doi: 10.1016/j.tips.2019.11.003. Epub 2019 Dec 10.
Results Reference
background

Learn more about this trial

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

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