Phase Ib of L-NMMA and Pembrolizumab

Part of paid clinical trials in Houston, Texas.

Sponsor
The Methodist Hospital Research Institute
Study ID
NCT03236935
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • L-NMMA — DRUG
    pan-nitric oxide synthase inhibitor
  • Pembrolizumab — DRUG
    PD-1 inhibitor

Study Details

The purpose of this Phase Ib study is to test the safety of NG-monomethyl-L-arginine (L-NMMA) and pembrolizumab when used together in participants with melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), classical Hodgkin lymphoma (cHL), urothelial carcinoma, Cervical Cancer, Esophageal Cancer, Gastric Cancer, Hepatocellular Carcinoma, Merkel Cell Carcinoma, Primary Mediastinal Large B-cell Lymphoma, Renal Cell Carcinoma, Small Cell Lung Cancer, microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) cancer or for the Treatment of Adult Patients with Unresectable or Metastatic Tumor Mutational Burden-High Solid Tumors. Pembrolizumab is a type of treatment that stimulates the immune system to attack cancer cells. The immune system is normally the body's first defense against threats like cancer. However, sometimes cancer cells produce signals like programmed death-1 (PD-1) that prevent the immune system from detecting and killing them. Pembrolizumab blocks PD-1 so your immune system can detect and attack cancer cells. To help further boost the cancer-fighting ability of your immune system, L-NMMA will be used along with pembrolizumab. L-NMMA is a nitric oxide synthase inhibitor. The presence of nitric oxide synthase in the area around the cancer cells blocks the cancer-fighting ability of the immune system. Thus, the use of L-NMMA and pembrolizumab together may make the immune system work harder to attack and destroy the cancer cells.

Key Dates

Start date
Aug 27, 2018
Status verified
Mar 2026
Primary completion
Oct 31, 2021
Completion
Apr 22, 2022

Study Design

Enrollment
12 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: L-NMMA Dose Level -1, 12.5 mg/kg
    Cohort -1: L-NMMA and pembrolizumab will be administered for 6 cycles. Cycle length will be 21 days. L-NMMA will be administered as a 2-hour intravenous (IV) infusion on Days 1-5 at each cycle. L-NMMA Dose will be 12.5 mg/kg. L-NMMA dose will escalate/de-escalate based on the occurrence of dose-limiting toxicities. Pembrolizumab at a fixed dose of 200 mg will be IV infused over 30 minutes on Day 5 at each cycle. Pembrolizumab will be administered 1 hour after L-NMMA infusion on Day 5 at each cycle. Subjects without disease progression after 6 cycles of L-NMMA and pembrolizumab will continue pembrolizumab until disease progression or unacceptable AEs.
  • Experimental: L-NMMA Dose Level 0 (starting dose), 15.0 mg/kg
    Cohort 0: L-NMMA and pembrolizumab will be administered for 6 cycles. Cycle length will be 21 days. L-NMMA will be administered as a 2-hour intravenous (IV) infusion on Days 1-5 at each cycle. L-NMMA Dose will be 15.0 mg/kg. L-NMMA dose will escalate/de-escalate based on the occurrence of dose-limiting toxicities. Pembrolizumab at a fixed dose of 200 mg will be IV infused over 30 minutes on Day 5 at each cycle. Pembrolizumab will be administered 1 hour after L-NMMA infusion on Day 5 at each cycle. Subjects without disease progression after 6 cycles of L-NMMA and pembrolizumab will continue pembrolizumab until disease progression or unacceptable AEs.
  • Experimental: L-NMMA Dose Level 1, 20 mg/kg
    Cohort 1: L-NMMA and pembrolizumab will be administered for 6 cycles. Cycle length will be 21 days. L-NMMA will be administered as a 2-hour intravenous (IV) infusion on Days 1-5 at each cycle. L-NMMA Dose will be 20 mg/kg. L-NMMA dose will escalate/de-escalate based on the occurrence of dose-limiting toxicities. Pembrolizumab at a fixed dose of 200 mg will be IV infused over 30 minutes on Day 5 at each cycle. Pembrolizumab will be administered 1 hour after L-NMMA infusion on Day 5 at each cycle. Subjects without disease progression after 6 cycles of L-NMMA and pembrolizumab will continue pembrolizumab until disease progression or unacceptable AEs.

Primary Outcome Measure

Maximum Tolerated Dose (MTD) [ Time Frame: 18 weeks ]

Locations (1)

FacilityCityStateZIPSite coordinators
Houston Methodist Cancer CenterHoustonTexas77030-

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