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QUILT-3.017: Study of NEO-201 in Solid Tumors

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: NCT03476681
Recruitment Status : Recruiting
First Posted : March 26, 2018
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
Precision Biologics, Inc

Tracking Information
First Submitted Date  ICMJE February 26, 2018
First Posted Date  ICMJE March 26, 2018
Last Update Posted Date August 12, 2019
Actual Study Start Date  ICMJE January 18, 2019
Estimated Primary Completion Date October 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
Determine Maximum Tolerated Dose (MTD), 2 weeks after 2 doses of intravenous NEO-201 given every 2 weeks. [ Time Frame: 1.5 years ]
The MTD will be the dose level at which no greater than 1/6 subjects has a dose limiting toxicity (DLT), and the next higher dose level has at least 2 subjects with a DLT.
Original Primary Outcome Measures  ICMJE
 (submitted: March 22, 2018)
Determine Maximum Tolerated Dose (MTD), 2 weeks after 2 doses of intravenous NEO-201 given every 2 weeks. [ Time Frame: One year ]
The MTD will be the dose level at which no greater than 1/6 subjects has a dose limiting toxicity (DLT), and the next higher dose level has at least 2 subjects with a DLT.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2018)
  • Toxicities including treatment emergent adverse events and the character and incidence of Grade 1-4 toxicities. [ Time Frame: 2.5 years ]
    • Describe the character and incidence of Grade 1-4 toxicities based on CTCAE v5.0 that occur in adults receiving monotherapy with NEO-201.
  • Characterize the area under the concentration-time curve (AUC) of the pharmacokinetics (PK) of NEO-201 monotherapy. [ Time Frame: 57 days ]
    • Drug exposure will be estimated using the area under the concentration-time curve (AUC). The AUC from time zero to the time of each quantifiable sample (AUClast) will be calculated using the linear trapezoidal method. Quantifiable samples will be drawn at the following time points Cycle 1: • Day 1 (Dose 1): Pre dose Immediately after end of study drug infusion (no longer than 3 minutes post) 1 (±5 min) hour and 4 (±10 min) hours post infusion (Cycle 1 only)
    • Day 2: 24 hours (±1 hour) post infusion(Cycle 1 only)
    • Day 4: 72 (±3 hours) hours post infusion (Cycle 1 only)
    • Day 8: 7 days (±3 hours) post infusion (Cycle 1 only)
    • Day 14 (Dose 2): pre dose and immediately after end of study drug infusion (no longer than 3 minutes post)
    Cycle 2:
    • Day 1 (Dose 3): pre and post dose.
    • Day 14 (Dose 4): pre dose and post dose.
    • Day 28 (End of 2nd Cycle Evaluation) (±4 days)
  • Characterize Peak Plasma Concentration (Cmax) of the pharmacokinetics (PK) of NEO-201 [ Time Frame: 57 days ]
    The reported maximum plasma concentration (Cmax) (Peak concentration) will be determined using a precise validated Elisa method for each dose level on samples collected at the following time points: Cycle 1: • Day 1 (Dose 1): Immediately after end of study drug infusion (no longer than 3 minutes post) 1 (±5 min) hour and 4 (±10 min) hours post infusion (Cycle 1 only)
    • Day 2: 24 hours (±1 hour) post infusion(Cycle 1 only)
    • Day 4: 72 (±3 hours) hours post infusion (Cycle 1 only)
    • Day 8: 7 days (±3 hours) post infusion (Cycle 1 only)
    • Day 14 (Dose 2): immediately after end of study drug infusion (no longer than 3 minutes post)
    Cycle 2:
    • Day 1 (Dose 3): immediately following after end of study drug infusion (no longer than 3 minutes post)
    • Day 14 (Dose 4): immediately after end of study drug infusion (no longer than 3 minutes post)
    • Day 28 (End of 2nd Cycle Evaluation) (±4 days)
  • Characterize the Minimum Plasma Concentration (Cmin) of the pharmacokinetics (PK) of NEO-201 [ Time Frame: 57 days ]
    The reported minimum plasma concentration (Cmin) (Trough concentration) will be determined using a precise validated Elisa method for each dose level on samples collected at the following time points: Cycle 1: • Day 1 (Dose 1): Pre dose Immediately after end of study drug infusion (no longer than 3 minutes post) 1 (±5 min) hour and 4 (±10 min) hours post infusion (Cycle 1 only)
    • Day 2: 24 hours (±1 hour) post infusion(Cycle 1 only)
    • Day 4: 72 (±3 hours) hours post infusion (Cycle 1 only)
    • Day 8: 7 days (±3 hours) post infusion (Cycle 1 only)
    • Day 14 (Dose 2): pre dose and immediately after end of study drug infusion (no longer than 3 minutes post)
    Cycle 2:
    • Day 1 (Dose 3): pre dose and immediately following after end of study drug infusion (no longer than 3 minutes post)
    • Day 14 (Dose 4): pre dose and immediately after end of study drug infusion (no longer than 3 minutes post)
    • Day 28 (End of 2nd Cycle Evaluation) (±4 days)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE QUILT-3.017: Study of NEO-201 in Solid Tumors
Official Title  ICMJE Phase 1 With Expansion Cohorts in a Study of NEO-201 in Adults With Chemo-Resistant Solid Tumors
Brief Summary This is an open label, first-in-human, phase 1, dose escalation study to determine the safety including dose limiting toxicity (DLT) and maximal tolerated dose of the monoclonal antibody NEO-201 in adults with solid tumors (cancer) which has not responded to standard treatments.
Detailed Description

The experimental drug called NEO-201 (the "study drug") is a monoclonal antibody that is being tested and is not approved for use in the United States by the FDA.

The primary purpose of this first in human targeted phase 1 open-label study with NEO-201 in subjects with advanced solid tumors is to determine the safety of NEO-201 and select a dose for phase 2 clinical trials.

NEO-201 will be given in four increasing doses to make sure it is safe. NEO-201 will start at a low dose (1 mg/kg) and be increased 3 times (2, 4, 6 mg/kg) over the period of the study in different groups of subjects. Subjects who enroll during the early stages of the study, will receive a lower dose of NEO-201, those who enroll later, will receive a higher dose that may be associated with more side effects.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
NEO-201 will be given in four increasing doses, it will start at a low dose (1 mg/kg) and be increased 3 times (2, 4, 6 mg/kg) over the period of the study in 4 different groups of patients. Each group will enroll 3-6 patients to a maximum of 24 patients.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Pancreatic Cancer
  • Adenocarcinoma of Lung
  • Squamous Cell Lung Cancer
  • Breast Cancer
  • Mucinous Carcinoma of Ovary
  • Signet Ring Cell Carcinoma of Ovary
Intervention  ICMJE Drug: NEO-201
NEO-201 will be given intravenously every 2 weeks.
Study Arms  ICMJE Experimental: NEO-201
Subjects will receive the assigned dose of NEO-201 intravenously, once every 2 weeks for a total of 4 doses (57 days). This course will be repeated in the absence of disease progression or unacceptable toxicity.
Intervention: Drug: NEO-201
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 22, 2018)
35
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 15, 2022
Estimated Primary Completion Date October 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age: >/=18 years
  • Diagnosis:

    • Histologically or cytologically confirmed recurrent, locally advanced unresectable or metastatic cancer confirmed by the Laboratory of Pathology, NCI.
    • Must have progressed after (or been intolerant of) standard therapy known to provide clinical benefit for respective tumor type and for which standard curative options do not exist or are no longer effective or tolerable.
    • Must have archived tissue (10 unstained slides or tissue block), or must have tumor which can be safely biopsied percutaneously and be willing to undergo a tumor biopsy.
    • Must have colorectal cancer, pancreatic cancer, adenocarcinoma of the lung, squamous cell lung cancer, breast cancer, and mucinous and signet cell ovarian cancer (cancer types in which tumor samples (> 50%) historically stain positive for NEO-201 expression).
  • Measurable disease (by RECIST)
  • ECOG </=2; or Karnofsky performance status of 50%
  • Laboratory Function: (within 21 days of the first dose of study drug)

    • Hemoglobin > 9 g/dL, or on stable doses (hematocrit stable within 1 gram and dose stable for one month) of erythropoietin or similar medication.
    • Absolute neutrophil count (ANC) >/=1,500/mm3.
    • Platelets >/=100,000/mm3.
    • Total bilirubin </= 2.0 mg/dL
    • ALT and AST </= 3 times the ULN, or, if the subject has liver metastases, </= 5 times the ULN.
    • Creatinine </= 1.5 mg/dL or creatinine clearance > 40 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
  • Voluntary written informed consent before performance of any study-related procedure that is not part of normal medical care.
  • Prior Therapy:

    • At least 14 days must have elapsed since treatment with oral tyrosine kinase inhibitors, or until toxicities associated with TKI therapy have resolved.
    • At least 21 days must have elapsed since treatment with previous monoclonal antibodies, or until toxicities associated with mAb therapy have resolved.
    • At least 4 weeks must have elapsed since any chemotherapeutic agents at the time of enrollment (or 6 weeks for regimens containing BCNU or mitomycin C).
    • At least 2 weeks must have elapsed since any systemic corticosteroids at the time of enrollment
    • At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
    • XRT: At least 7 days after local palliative XRT (small port)
  • Must have recovered from any acute toxicity related to prior therapy, except for alopecia. Toxicity should be ≤ grade 1, or ≤ grade 2 for peripheral neuropathy, or returned to baseline.
  • Expected to be able to remain on a study protocol for at least 8 weeks.
  • Females either post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control for the duration of the study.

Males must agree to use adequate contraception prior to the study, for the duration of study participation, and 2 weeks after completion of NEO-201 administration.

Exclusion Criteria:

  • History of disseminated or uncontrolled brain metastases or central nervous system disease. Brain metastases will be considered controlled if SD on two consecutive brain MRIs, performed at least 2 months apart, and subject is without seizures.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to NEO-201 or other agents used in this study.
  • Any major surgery within 14 days of enrollment.
  • Receiving any other investigational agents.
  • No archival tissue available and a lesion(s) that cannot be safely biopsied via percutaneous route, or is unwilling to undergo biopsy.
  • Has an uncontrolled concomitant illness including, but not limited to, ongoing or active infection, uncontrolled diabetes mellitus, symptomatic congestive heart failure, unstable angina pectoris, hypokalemia, family history of Long QT Syndrome or presence of cardiac arrhythmia.
  • HIV-positive subjects on combination antiretroviral therapy are ineligible because of the unknown potential for pharmacokinetic interactions with NEO-201. In addition, these subjects are at increased risk of lethal infections which could complicate the toxicity assessment of this study. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated.
  • Subject has other serious medical illness, including a second malignancy, or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Pregnant women are excluded from this study because the potential for teratogenic or abortifacient effects due to NEO-201 is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with NEO-201, breastfeeding should be discontinued if the mother is treated with NEO-201.
  • Subjects with marked baselined prolongation of QT/QTc interval (e.g. 2 ECGs on separate dates demonstrating QTc interval > 450 ms).
  • Use of concomitant medications associated with a high risk of DtP and prolongation of QT/QTc interval
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cynthia Boyle 240-760-6006 cynthia.boyle@nih.gov
Contact: Nicole Houston, BSN, RN 240-760-6127 houstonnd@mail.nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03476681
Other Study ID Numbers  ICMJE PB-1801
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Precision Biologics, Inc
Study Sponsor  ICMJE Precision Biologics, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christina M Annunziata, MD,PhD National Cancer Institute (NCI)
PRS Account Precision Biologics, Inc
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP