An open-label, first in human study investigating NVG-111 in CLL/MCL
Research type
Research Study
Full title
An open-label, phase 1/2, first in human study investigating the safety, tolerability, pharmacokinetics and efficacy of NVG-111 in subjects with relapsed/refractory chronic lymphocytic leukaemia and mantle cell lymphoma
IRAS ID
284930
Contact name
Peter Phillips
Contact email
Sponsor organisation
NovalGen
Eudract number
2020-000820-20
Clinicaltrials.gov Identifier
Duration of Study in the UK
5 years, 4 months, 26 days
Research summary
Summary of Research
This trial is sponsored by a company called NovalGen. The drug, NVG-111, is a type of antibody treatment. It is "bispecific", which means it has two “arms”, one which attaches to the receptor on the cancer cell that is being targeted (a receptor called ROR1, which stands for Receptor tyrosine kinase-like Orphan Receptor 1), and one arm which attaches to T cells, cells in the immune system. The bispecific antibody joins T cells to the cancer cell, this should trigger the immune system to kill the cancer cell.
This is the first time NVG-111 will be tested in humans. The study aims to find out if the drug is safe and shows any benefit in patients with blood and lymph gland cancers called chronic lymphocytic leukaemia and mantle cell lymphoma; up to 90 patients will be included, 36 in Part A (testing safety of different doses) and then 54 in Part B (testing efficacy one dose level). NVG-111 will be added to patients' existing treatment. It is given into a vein by continuous infusion using a minipump which patients carry with them.
Patients will be in the study for up to 32 months, visiting the site up to 35 times. All patients receive treatment for 11 weeks, in 3 cycles (each cycle includes 21 days treatment then a 7 day break). They will be admitted to stay at the clinical unit/hospital for the first 4 days of Cycle 1. The first 3 patients will also be admitted to stay for the first 4 days of Cycle 2 and Cycle 3. At the end of Cycle 3, if tests show the patient might benefit from longer treatment, they receive further three cycles (Cycles 4, 5 and 6).The follow up period is up to 2 years to understand long term effects.Summary of Results
This study was the first time a new drug called NVG-111 was tested in humans, aiming to treat certain hard-to-treat cancers known as ROR1+ malignancies. The drug was given to patients with blood cancers and solid tumours. The main goal was to see if the drug was safe, how well people tolerated it and to identify what dose of the drug should be given to humans in future studies. The study also aimed to see how it behaved in the body and how well it worked.Although the study was stopped early due to unexpected issues with supplies of the drug, it still provided useful insights. The study was not stopped early due to any safety reasons. Several different strengths of NVG-111 were found to be safe and well tolerated by patients with blood cancers and solid tumours. It was also discovered that the safety of the drug was improved for patients with solid tumours if they were given dexamethasone (a steroid medication used to treat inflammation and lower the body's immune response [the body's way of defending itself against threats like bacteria, viruses, and other invaders]) before they were given NVG-111.
Some side effects were observed that were linked to the drug, but they were already expected for the drug. These important side effects included the following:
• Headaches;
• An immune reaction called cytokine release syndrome [which is inflammation that happens when your immune system releases large amounts of a protein called cytokines into your bloodstream]); • Neurological symptoms (meaning related to the nervous system, which includes the brain, spinal cord, and all the nerves in the body) including immune effector cell-associated neurotoxicity syndrome (an immune reaction that causes swelling and damage in the brain).No unexpected safety problems were found. Two patients with solid tumours died weeks after stopping treatment, but their deaths were not caused by the drug.
No major changes were seen in blood tests, heart monitoring, or other health checks.
Despite the early end of the study, the safety profile of NVG-111 was encouraging and supported further research. Based on these findings, a next-generation version of the drug has been developed. It lasts longer in the body for patient convenience and includes a built-in safety feature to help control its effects.
REC name
London - Chelsea Research Ethics Committee
REC reference
20/LO/1117
Date of REC Opinion
30 Oct 2020
REC opinion
Further Information Favourable Opinion