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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04140526
Recruitment Status : Recruiting
First Posted : October 28, 2019
Last Update Posted : May 5, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OncoC4, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
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 Merkel Cell Carcinoma Pancreas Cancer Gastric Cancer Esophageal Cancer Gastroesophageal Junction Adenocarcinoma Cervical Cancer Drug: ONC-392 Drug: Pembrolizumab Drug: Osimertinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 413 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Open label
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 16, 2020
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2024


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: 0.1 mg/kg (cohort 1), 0.3 mg/kg (cohort 2), 1 mg/kg (cohort 3), 3 mg/kg (cohort 4) and 10 mg/kg (cohort 5) of ONC-392 as monotherapy every 21 days (Q3W). The treatment will continue for up to 1 year, or discontinued upon disease progression, or unacceptable toxicity, or voluntary withdraw. 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, H-M monotherapy expansion cohorts will further assess the safety and efficacy of ONC-392 in dose level of RP2D-M as monotherapy in pancreatic cancer, triple negative breast cancer and non small cell lung cancer with driver mutations.

Drug: ONC-392
ONC-392 will be given by intravenous infusion, once every 21 days (Q3W).
Other Name: A humanized anti-CTLA4 IgG1 monoclonal antibody made by OncoImmune, 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 RP2D-C dose level and Pembrolizumab combination therapy in non small cell lung cancer, melanoma and Merkel cell carcinoma.

Drug: ONC-392
ONC-392 will be given by intravenous infusion, once every 21 days (Q3W).
Other Name: A humanized anti-CTLA4 IgG1 monoclonal antibody made by OncoImmune, Inc.

Drug: Pembrolizumab
Pembrolizumab will be given intravenous (IV) infusion at 200 mg/cycle, once every 21 days (Q3W).
Other Name: Keytruda

Experimental: ONC-392 in combination with Osimertinib
The Part B2 study will test ONC-392 intravenous (IV) infusion, Q3W, in combination with fixed dose of Osimertinib of 80 mg PO, QD in non small cell lung cancer with EGFR mutations. The Part B2 will start at one level below RP2D-M dose for ONC-392. The goal is to define the RP2D-C-TKI.
Drug: ONC-392
ONC-392 will be given by intravenous infusion, once every 21 days (Q3W).
Other Name: A humanized anti-CTLA4 IgG1 monoclonal antibody made by OncoImmune, Inc.

Drug: Osimertinib
Osimertinib will be given orally 80 mg, once a day.
Other Name: TAGRISSO




Primary Outcome Measures :
  1. Dose limiting toxicity (DLT) in monotherapy [ Time Frame: 21 days ]
    The number of subjects who have dose limiting toxicity during the first cycle of study drug, ONC-392, administration.

  2. Maximal tolerable dose (MTD) in monotherapy [ Time Frame: 21 days ]
    The study drug, ONC-392, dose level that has two out of six subjects who have dose limiting toxicity.

  3. Recommended Phase II Dose (RP2D) [ Time Frame: 21 days ]
    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.

  4. Rate of treatment related adverse events (TRAE) according to CTCAE v5.0 [ Time Frame: One year ]
    The safety profile will be presented as tabulated TRAE.


Secondary Outcome Measures :
  1. The serum half life of the study drug, ONC-392, in monotherapy. [ Time Frame: 12 weeks ]
    To determine the drug concentration in serum samples that are taken in various timepoints during the treatment in order to calculate drug half life.

  2. The serum half life of the study drug, ONC-392, in combination therapy with Pembrolizumab. [ Time Frame: 12 weeks ]
    To determine the drug concentration in serum samples that are taken in various timepoints during the treatment in order to calculate drug half life.

  3. Objective Response Rate (ORR) [ Time Frame: 1 year ]
    To determine the objective response rate based on RECIST v1.1.

  4. Progression Free Survival (PFS) [ Time Frame: 1 year ]
    To determine the progression free survival based on RECIST 1.1 and iRECIST.

  5. Overall Survival (OS) [ Time Frame: 1 year ]
    To determine the overall survival.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, Merkel cell carcinoma, Head and Neck cancer, ovarian cancer, and other solid tumors 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.
  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 B1 and Part C Arm D to G, the patients that are deemed to be not suitable for Pembrolizumab.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04140526


Contacts
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Contact: Pan Zheng, MD, PhD 202 751 6823 pzheng@oncoc4.com
Contact: Martin Devenport, PhD 4102070582 mdevenport@oncoc4.com

Locations
Show Show 31 study locations
Sponsors and Collaborators
OncoC4, Inc.
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Tianhong Li, MD University of California, Davis
Publications:

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Responsible Party: OncoC4, Inc.
ClinicalTrials.gov Identifier: NCT04140526    
Other Study ID Numbers: ONC-392-001
4R44CA250824-02 ( U.S. NIH Grant/Contract )
20193108 ( Other Identifier: WIRB )
First Posted: October 28, 2019    Key Record Dates
Last Update Posted: May 5, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Carcinoma
Lung Neoplasms
Small Cell Lung Carcinoma
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Adenocarcinoma
Endocrine Gland Neoplasms
Endocrine System Diseases
Pancreatic Diseases
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Infections
Tumor Virus Infections