Clinical Trials /

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

NCT03476681

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Lung Adenocarcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: QUILT-3.017: Study of NEO-201 in Solid Tumors
  • Official Title: Phase 1 With Expansion Cohorts in a Study of NEO-201 in Adults With Chemo-Resistant Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: PB-1801
  • NCT ID: NCT03476681

Conditions

  • Colorectal Cancer
  • Pancreatic Cancer
  • Adenocarcinoma of Lung
  • Squamous Cell Lung Cancer
  • Breast Cancer
  • Mucinous Carcinoma of Ovary
  • Signet Ring Cell Carcinoma of Ovary

Interventions

DrugSynonymsArms
NEO-201NEO-201

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
NEO-201ExperimentalSubjects 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.
  • NEO-201

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine Maximum Tolerated Dose (MTD), 2 weeks after 2 doses of intravenous NEO-201 given every 2 weeks.
Time Frame:1.5 years
Safety Issue:
Description: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

Measure:Toxicities including treatment emergent adverse events and the character and incidence of Grade 1-4 toxicities.
Time Frame:2.5 years
Safety Issue:
Description:• Describe the character and incidence of Grade 1-4 toxicities based on CTCAE v5.0 that occur in adults receiving monotherapy with NEO-201.
Measure:Characterize the area under the concentration-time curve (AUC) of the pharmacokinetics (PK) of NEO-201 monotherapy.
Time Frame:57 days
Safety Issue:
Description:• 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)
Measure:Characterize Peak Plasma Concentration (Cmax) of the pharmacokinetics (PK) of NEO-201
Time Frame:57 days
Safety Issue:
Description: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)
Measure:Characterize the Minimum Plasma Concentration (Cmin) of the pharmacokinetics (PK) of NEO-201
Time Frame:57 days
Safety Issue:
Description: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)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Precision Biologics, Inc

Trial Keywords

  • 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

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