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

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ClinicalTrials.gov Identifier: NCT03476681
Recruitment Status : Recruiting
First Posted : March 26, 2018
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
Precision Biologics, Inc

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Pancreatic Cancer Adenocarcinoma of Lung Squamous Cell Lung Cancer Breast Cancer Mucinous Carcinoma of Ovary Signet Ring Cell Carcinoma of Ovary Drug: NEO-201 Phase 1

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
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
Official Title: Phase 1 With Expansion Cohorts in a Study of NEO-201 in Adults With Chemo-Resistant Solid Tumors
Estimated Study Start Date : October 15, 2018
Estimated Primary Completion Date : October 15, 2019
Estimated Study Completion Date : October 15, 2022


Arm Intervention/treatment
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.
Drug: NEO-201
NEO-201 will be given intravenously every 2 weeks.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. 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)

  4. 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)



Information from the National Library of Medicine

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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:

  • 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

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): NCT03476681


Contacts
Contact: Cynthia Boyle 240-760-6006 cynthia.boyle@nih.gov
Contact: Nicole Houston, BSN, RN 240-760-6127 houstonnd@mail.nih.gov

Locations
United States, Maryland
National Cancer Institute Recruiting
Bethesda, Maryland, United States, 20892
Contact: Cynthia Boyle    240-760-6006    cynthia.boyle@nih.gov   
Contact: Nicole Houston, BSN, RN    240-760-6127    houstonnd@mail.nih.gov   
Sponsors and Collaborators
Precision Biologics, Inc
Investigators
Principal Investigator: Christina M Annunziata, MD,PhD National Cancer Institute (NCI)

Responsible Party: Precision Biologics, Inc
ClinicalTrials.gov Identifier: NCT03476681     History of Changes
Other Study ID Numbers: PB-1801
First Posted: March 26, 2018    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Precision Biologics, Inc:
NEO-201
Monoclonal Antibody
Colorectal Cancer
Pancreatic Cancer
Adenocarcinoma of Lung
Squamous Cell Lung Cancer
Breast Cancer
Mucinous Carcinoma of Ovary
Signet Ring Cell Carcinoma of Ovary

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Adenocarcinoma
Pancreatic Neoplasms
Lung Neoplasms
Carcinoma, Signet Ring Cell
Adenocarcinoma, Mucinous
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Cystic, Mucinous, and Serous
Ovarian Diseases
Adnexal Diseases