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BRIEF TITLE: A Phase I Study to Evaluate the Safety of Trigriluzole (FC-4157/BHV-4157) in Combination With PD-1 Blocking Antibodies

A Phase I Study to Evaluate the Safety of Trigriluzole (FC-4157/BHV-4157) in Combination With PD-1 Blocking Antibodies

  • Org Study ID: 051707
  • Secondary ID: NCI-2017-01155,Pro20170000453,051707,P30CA072720
  • NCT ID: NCT03229278
  • NCT Alias:
  • Sponsor: Rutgers, The State University of New Jersey - Other
  • Source: Rutgers, The State University of New Jersey

Brief Summary

This phase I trial studies the best dose and side effects of trigriluzole in combination with nivolumab and pembrolizumab in treating patients with solid malignancies or lymphoma that has spread to other places in the body or cannot be removed by surgery. Trigriluzole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab and pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving trigriluzole in combination with nivolumab and pembrolizumab may work better at treating patients with solid malignancies or lymphoma.

Detailed Description


I. The primary objective of this study is to determine the safety of trigriluzole in
combination with PD-1 inhibiting antibodies, and to define a maximum tolerated dose (MTD) of
trigriluzole in combination therapy.


I. To characterize the efficacy of the combination therapy. II. To identify markers of
response to trigriluzole in the tumor microenvironment.

OUTLINE: This is a dose-escalation study of trigriluzole.

Patients receive trigriluzole orally (PO) every other day (QOD), twice daily (BID), every
morning (QAM) or every bedtime (QHS) on days -14 to -1. Patients then receive nivolumab
intravenously (IV) over 60 minutes every 2 weeks beginning week 1 and trigriluzole PO QOD,
BID, QAM or QHS. Once the MTD of trigriluzole with nivolumab is identified, patients receive
pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and trigriluzole PO.
Treatment repeats for up to 1 year in the absence of disease progression or unacceptable

After completion of study treatment, patients are followed up every 12 weeks for up to 3

Overal Status Start Date Phase Study Type
Recruiting August 17, 2017 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Maximum tolerated dose (MTD))/recommended phase 2 dose of trigriluzole

Primary Outcome 1 - Time Frame: Up to 3 years


  • Lymphoma
  • Metastatic Malignant Solid Neoplasm
  • Metastatic Melanoma
  • Metastatic Renal Cell Cancer
  • Recurrent Bladder Carcinoma
  • Recurrent Classical Hodgkin Lymphoma
  • Recurrent Head and Neck Squamous Cell Carcinoma
  • Recurrent Lymphoma
  • Recurrent Malignant Solid Neoplasm
  • Recurrent Renal Cell Carcinoma
  • Stage III Bladder Cancer
  • Stage III Lymphoma
  • Stage III Non-Small Cell Lung Cancer AJCC v7
  • Stage III Renal Cell Cancer
  • Stage III Skin Melanoma
  • Stage IIIA Non-Small Cell Lung Cancer AJCC v7
  • Stage IIIA Skin Melanoma
  • Stage IIIB Non-Small Cell Lung Cancer AJCC v7
  • Stage IIIB Skin Melanoma
  • Stage IIIC Skin Melanoma
  • Stage IV Bladder Cancer
  • Stage IV Lymphoma
  • Stage IV Non-Small Cell Lung Cancer AJCC v7
  • Stage IV Renal Cell Cancer
  • Stage IV Skin Melanoma
  • Stage IVA Bladder Cancer
  • Stage IVB Bladder Cancer
  • Unresectable Head and Neck Squamous Cell Carcinoma
  • Unresectable Solid Neoplasm


Inclusion Criteria:

- Patients must have histologically confirmed solid malignancy or lymphoma that is
metastatic or unresectable

- There is reasonable expectation of response to pembrolizumab or nivolumab, and one of
the drugs is available from the commercial supply; this includes (but is not limited
to) the following tumor types: melanoma, non-small cell lung cancer, renal cell
carcinoma, squamous cell carcinoma of the head and neck, bladder cancer, and classic
Hodgkin lymphoma

- The patient must have failed at least one line of standard treatment, with the
following exceptions in which a PD-1 antibody is Food and Drug Administration (FDA)
approved in the first-line setting:

- Melanoma patients

- Non-small cell lung cancer patients without EGFR or ALK genomic tumor aberrations
whose tumors have high PD-L1 expression (tumor proportion score [TPS] >= 50%) as
determined by an FDA-approved test

- Patients must give informed consent

- Prior chemotherapy, immunotherapy, radiotherapy or major surgery (including radiation
therapy or surgery for treatment of brain metastases) must be completed at least 3
weeks before study entry; prior PD-1 or PD-L1 therapy is acceptable

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =<

- Hemoglobin > 8.0 mg/dL (without transfusion in the preceding 7 days)

- Platelets >= 70,000 /uL

- Total bilirubin within normal institutional limits (patients with Gilbert's syndrome
must have a total bilirubin < 3.0 mg/dL)

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2
X institutional upper limit of normal (ULN)

- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 X
institutional ULN

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
10 mm by computed tomography (CT) scan, positron emission tomography (PET)/CT scan,
magnetic resonance imaging (MRI) or caliper/ruler measurement by clinical exam; lymph
nodes: to be considered pathologically enlarged and measurable, a lymph node must be
>= 15 mm in short axis when assessed by CT scan; lesions that have been radiated in
the advanced setting cannot be included as sites of measurable disease unless clear
tumor progression has been documented in these lesions since the end of radiation

- Ability to swallow pills

Exclusion Criteria:

- Systemic immunosuppressive medications such as steroids; the following steroid
formulations are permitted: intranasal, intra-articular, and inhaled steroids

- History of immune-related adverse event from prior immunotherapy treatment that has
not improved to grade 0-1; subjects with grade 2 hypothyroidism and grade 2 adrenal
insufficiency requiring continued medical treatment may enroll provided that they are
asymptomatic and stable on their dose of hormone replacement

- Serious concomitant systemic disorders (including active infections) that would
compromise the safety of the patient or compromise the patient?s ability to complete
the study, at the discretion of the investigator, including active autoimmune disease
requiring treatment within the past 30 days

- Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalents) or other systemic immunosuppressive medications within 14 days
of study drug administration; inhaled or topical steroids and adrenal replacement
doses < 10 mg daily prednisone equivalents are permitted in the absence of active
autoimmune disease; patients are permitted to use topical, ocular, intra-articular,
intranasal, and inhalational corticosteroids (with minimal systemic absorption)'
physiologic replacement doses of systemic corticosteroids are permitted, even if < 10
mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis
(e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g.,
delayed-type hypersensitivity reaction caused by contact allergen) is permitted

- Second primary malignancy, except those second primary malignancies that are not
considered to be competing causes of death in the opinion of the treating
investigator; examples include: in situ carcinoma of the cervix, adequately treated
non-melanoma carcinoma of the skin, or other malignancy treated at least 5 years
previously with no evidence of recurrence

- Patients with active, untreated central nervous system (CNS) metastases will be
excluded from this clinical trial; patients who have brain metastases that been
treated with radiation therapy or surgery will be required to have a washout period of
at least 3 weeks prior to study entry, must be neurologically asymptomatic, and must
not require systemic steroids

- Women of child-bearing potential and men must agree to use adequate contraception
prior to the start of treatment, for the duration of treatment, and for 5 months after
last dose of study treatment

- Patients with immune deficiency have impaired immune responses, therefore, known human
immunodeficiency virus (HIV)-positive patients are excluded from the study
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Ann (Annie) Silk

Role: Principal Investigator

Affiliation: Rutgers Cancer Institute of New Jersey


Facility Status Contact
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey 08903
United States
Recruiting Ann (Annie) W. Silk