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.
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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 toxicity. After completion of study treatment, patients are followed up every 12 weeks for up to 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
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.
Time frame: Four weeks
Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)
A DLT was any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) that was possibly Trigriluzole or Nivolumab related. CTCAE 3.0 Grade 3 is a severe AE and Grade 4 is a life- threatening or disabling AE. DLTs were collected to determine the Maximum-Tolerated Dose (MTD), which is defined as the dose level below the dose at which 33% of participants experienced a DLT.
Time frame: Four weeks
Objective Response Rate Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1
Continuous variables will be presented by summary statistics (such as mean, median, standard error and 95% confidence intervals \[CI\]) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 95% CI).
Time frame: Up to 3 years
Overall Survival
Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).
Time frame: Up to 3 years
Time to Next Therapy or Death
Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).
Time frame: Up to 3 years
Freedom From New Metastases
Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).
Time frame: Up to 3 years
Landmark Survival Rates at 1 Year
Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).
Time frame: 1 year
Landmark Survival Rate at 2 Years
Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).
Time frame: 2 years
Duration of Response for Responding Patients
Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).
Time frame: Up to 3 years
Progression Free Survival
Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).
Time frame: Up to 3 years
Time to Treatment Failure
Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).
Time frame: Up to 3 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.