Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

NCT03229278 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: 051707NCI-2017-01155Pro20170000453P30CA072720
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD))/Recommended Phase 2 Dose of Trigriluzole

  The MTD of trigriluzole in combination with nivolumab will be identified. The MTD will then be tested in combination with pembrolizumab using the same escalate/de-escalate/stay rules. Data on the adverse event type, severity and frequency will be recorded.

  Four weeks

Secondary Outcomes (10)

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)

  Four weeks

• Objective Response Rate Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1

  Up to 3 years

• Overall Survival

  Up to 3 years

• Time to Next Therapy or Death

  Up to 3 years

• Freedom From New Metastases

  Up to 3 years

Study Arms (1)

Treatment (trigriluzole, nivolumab, pembrolizumab)

EXPERIMENTAL

Patients receive trigriluzole PO QOD, BID, QAM or QHS on days -14 to -1. Patients then receive nivolumab 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 toxicity.

Drug: Enzyme Inhibitor Therapy; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: Pembrolizumab

Interventions

Enzyme Inhibitor Therapy DRUG

Given trigriluzole PO

Treatment (trigriluzole, nivolumab, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (trigriluzole, nivolumab, pembrolizumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (trigriluzole, nivolumab, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (trigriluzole, nivolumab, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 =\< 2
• 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 therapy
• Ability to swallow pills

You may not qualify if:

• 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

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Related Publications (2)

• Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.

  PMID: 39462179 DERIVED

• Silk AW, Saraiya B, Groisberg R, Chan N, Spencer K, Girda E, Shih W, Palmeri M, Saunders T, Berman RM, Coric V, Chen S, Zloza A, Vieth J, Mehnert JM, Malhotra J. A phase Ib dose-escalation study of troriluzole (BHV-4157), an oral glutamatergic signaling modulator, in combination with nivolumab in patients with advanced solid tumors. Eur J Med Res. 2022 Jul 2;27(1):107. doi: 10.1186/s40001-022-00732-w.

  PMID: 35780243 DERIVED

MeSH Terms

Conditions

Lymphoma; Neoplasm Metastasis; Melanoma; Carcinoma, Renal Cell; Urinary Bladder Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Biren Saraiya - Associate Professor of Medicine Medical Director, Office of Human Research Servi
• Organization: Cancer Institute of New Jersey Rutgers

saraiybi@cinj.rutgers.edu

732-235-5773

Study Officials

• Biren Saraiya

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Medical Oncology

Study Record Dates

• First Submitted: July 18, 2017
• First Posted: July 25, 2017
• Study Start: October 3, 2017
• Primary Completion: October 20, 2022
• Study Completion: October 30, 2022
• Last Updated: December 6, 2023
• Results First Posted: December 6, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)