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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Small Cell Lung Cancer; Adenoid Cystic Carcinoma; Metastatic Renal Cell Carcinoma; Metastatic Colorectal Cancer; Gastric Cancer; Esophageal Cancer; Ovarian Cancer; Non Small Cell Lung Cancer; Metastatic Breast Cancer; Advanced Solid Tumor; Metastatic Melanoma; Pancreas Cancer; Metastatic Prostate Cancer; Urothelial Carcinoma; Gastroesophageal Junction Adenocarcinoma; Salivary Gland Cancer; Metastatic Head and Neck Carcinoma; Sarcomas
• Intervention / Treatment: Drug: ONC-392; Drug: Pembrolizumab

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.

1. 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.
2. 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.
3. 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.
4. 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%).
5. 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.
6. 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.
7. 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.
8. 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.
9. Arm J: Melanoma Mono Cohort, ONC-392 monotherapy, will enroll advanced/metastatic melanoma patients who are R/R to anti-PD-(L)1 immunotherapy.
10. 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.
11. 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.
12. 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.
13. 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.

• Study Type: Interventional
• Enrollment (Estimated): 914
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pan Zheng, MD, PhD; Phone Number: 202 751 6823; Email: pzheng@oncoc4.com
• Study Contact Backup: Name: Martin Devenport, PhD; Phone Number: 4102070582; Email: mdevenport@oncoc4.com

Study Locations

• Australia
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2305
      • Recruiting
      • Newcastle Private Hospital
      • Principal Investigator: Hiren Mandaliya, MD
  • Queensland
    • Southport, Queensland, Australia, 4120
      • Recruiting
      • Tasman Oncology Research
      • Principal Investigator: Andrew Hill, MD
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Cancer Research SA
      • Principal Investigator: Rohit Joshi, MD
    • Bedford Park, South Australia, Australia, 5042
      • Recruiting
      • Southern Oncology Clinical Research Unit
      • Principal Investigator: Ganessan Kitchenadasse, MD
• United States
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Recruiting
      • Highlands Oncology Group
      • Principal Investigator: Eric Schaefer
  • California
    • Davis, California, United States, 95817
      • Recruiting
      • University of California at Davis
      • Principal Investigator: Tianhong Li, MD, PhD
    • Downey, California, United States, 90241
      • Recruiting
      • The Oncology Institute of Hope and Innovation
      • Principal Investigator: Richy Agajanian, MD
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Cancer Center
      • Principal Investigator: Lorna Rodriguez, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital
      • Principal Investigator: Daniel Bowles, MD
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • Recruiting
      • University of Connecticut Medical Center
      • Principal Investigator: Susan Tannenbaum, MD
    • Norwalk, Connecticut, United States, 06856
      • Recruiting
      • Nuvance Health
      • Principal Investigator: Richard Frank, MD
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • MedStar Georgetown University Hospital
      • Principal Investigator: Aiwu He, MD, PhD
  • Florida
    • Atlantis, Florida, United States, 33462
      • Recruiting
      • Florida Cancer Specialists
      • Principal Investigator: Shaachi Gupta, MD
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida Health Cancer Center
      • Principal Investigator: Thomas George, MD
    • Ocala, Florida, United States, 34474
      • Recruiting
      • Ocala Oncology Florida Cancer Affiliates
      • Principal Investigator: Rama Balaraman, MD
    • Orlando, Florida, United States, 32804
      • Recruiting
      • AdventHealth Cancer Institute
      • Principal Investigator: Mark Socinski, MD
    • Pembroke Pines, Florida, United States, 33028
      • Recruiting
      • Memorial Cancer Institute
      • Principal Investigator: Adriana Milillo-Naraine, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Winship Cancer Institute
      • Principal Investigator: Nicole C Schmitt, MD
      • Principal Investigator: Nabil F Saba, MD
  • Kentucky
    • Lexington, Kentucky, United States, 40202
      • Recruiting
      • Norton Health
      • Principal Investigator: John Hamm, MD
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Recruiting
      • Greater Baltimore Medical Center
      • Principal Investigator: Mei Tang, MD, PhD
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • The Center for Cancer and Blood Disorders
      • Principal Investigator: Mark Goldstein, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Glenn Hanna, MD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Colin Weekes, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Medical Center
      • Principal Investigator: Ulka Vaishampayan, MD
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Atlantic Healthcare System
      • Principal Investigator: Eric Whitman, MD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Principal Investigator: Kenneth Yu, MD
      • Principal Investigator: Eileen O'Reilly, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati Medical Center
      • Principal Investigator: Amanda Jackson, MD
    • Columbus, Ohio, United States, 43219
      • Recruiting
      • Zangmeister Cancer Center
      • Principal Investigator: Sameh Mikhail, MD
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University James Cancer Center
      • Principal Investigator: Kai He, MD, PhD
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Recruiting
      • Pennsylvania Cancer Specialists & Research Institute (Formerly Gettysburg Cancer Center)
      • Principal Investigator: Satish Shah, MD
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State Cancer Institute
      • Principal Investigator: Patrick Ma, MD
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Prisma Health
      • Principal Investigator: Ki Young Chung, MD
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Recruiting
      • Tennessee Oncology Chattanooga Memorial Plaza
      • Principal Investigator: Edward Arrowsmith, MD
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology - Nashville
      • Principal Investigator: Meredith McKean, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Cancer Center
      • Principal Investigator: Jenny Chang, MD
    • Houston, Texas, United States, 77030
      • Recruiting
      • Oncology Consultants
      • Principal Investigator: Julio Peguero, MD
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah Huntsman Cancer Institute
      • Principal Investigator: Siwen Hu-Lieskovan, MD, PhD
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT/Virginia Cancer Specialists
      • Principal Investigator: Alexander Spira, MD
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington / Fred Hutchinson Cancer Center
      • Principal Investigator: Cristina P Rodriguez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ONC-392 Treatment as single agent; 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.	Drug: ONC-392; 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.; Other Names: A humanized anti-CTLA4 IgG1 monoclonal antibody made by OncoC4, Inc.
Experimental: ONC-392 in combination with pembrolizumab; 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.	Drug: ONC-392; 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.; Other Names: A humanized anti-CTLA4 IgG1 monoclonal antibody made by OncoC4, Inc.; Drug: Pembrolizumab; Pembrolizumab will be given intravenous (IV) infusion at 200 mg/cycle, once every 21 days (Q3W).; Other Names: Keytruda; MK3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	21 days
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.	21 days
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.	21 days
Rate of treatment related adverse events (TRAE) according to CTCAE v5.0	The safety profile will be presented as tabulated TRAE.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks
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.	12 weeks
Objective Response Rate (ORR)	To determine the objective response rate based on RECIST v1.1.	1 year
Progression Free Survival (PFS)	To determine the progression free survival based on RECIST 1.1 and iRECIST.	1 year
Overall Survival (OS)	To determine the overall survival.	1 year

Collaborators and Investigators

• Sponsor: OncoC4, Inc.
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Tianhong Li, MD, University of California, Davis

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: October 24, 2019
• First Submitted That Met QC Criteria: October 24, 2019
• First Posted (Actual): October 28, 2019

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Pancreatic Diseases; Salivary Gland Diseases; Mouth Neoplasms; Lung Neoplasms; Carcinoma; Small Cell Lung Carcinoma; Carcinoma, Adenoid Cystic; Pancreatic Neoplasms; Salivary Gland Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: ONC-392-001; 4R44CA250824-02 (U.S. NIH Grant/Contract); 20193108 (Other Identifier: WIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No