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ASH 2022: Dr. Parag Jasani on NVG-111, a ROR1 Targeting Bispecific T Cell Engager, for Chronic Lymphocytic Leukemia (CLL)

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

The Bottom Line:

Early data from an ongoing first-in-human phase 1 clinical trial shows that NVG-111 is generally well tolerated with a manageable safety profile. Though this was, first and foremost, a safety study, there was some preliminary evidence of efficacy.

Who Performed the Research and Where Was it Presented:

Dr. Parag Jasani from University College London Hospitals and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.


ROR1 is an enzyme that is expressed at high levels in many hematologic cancers, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). However, it is not found in normal healthy cells, which makes it an attractive therapeutic target. The experimental monoclonal antibody cirmtuzumab targets ROR1 and is currently being tested in phase 2 clinical trials (see our previous coverage here and here). In addition, a new drug in development is trying to target ROR1 differently.

In this interview, our own Dr. Brian Koffman interviewed Dr. Parag Jasani, a consultant hematologist with Royal Free London NHS Trust and University College London Hospitals. They discussed a first-in-human study of an experimental drug, NVG-111, a bispecific T cell engager. NVG-111 binds to ROR1 on cancer cells and CD3 on T cells, bringing the T cell close to the cancer cell so it can kill it.

Methods and Participants:

This phase 1 study evaluates the safety of NVG-111 in patients with relapsed/refractory CLL and MCL who have received ≥2 prior therapies. NVG-111 was administered as a continuous intravenous infusion over 21 days, followed by seven days off the drug (=1 cycle).


  • The data presented at ASH were results from 9 patients (8 CLL, 1 MCL).
  • Some of the common side effects that were observed included nausea (70%), headaches (60%), fatigue (50%), and cytokine release syndrome (40%). However, these were generally mild to moderate in intensity.
  • Cytokine release syndrome is a typical side effect of immunotherapies that activate T cells.
  • One patient experienced severe ICANS, neurotoxicity caused by T cells’ activation.
  • The first six patients received NVG-111 in combination with ibrutinib. These patients had already been on ibrutinib for at least 12 months prior but were still measurable residual disease (MRD) positive.
  • 5 out of 6 patients responded to treatment, and 2 of these 5 patients became MRD negative.
  • The subsequent 3 patients received NVG-111 as monotherapy. Of these patients, 1 responded to treatment, and 2 had their disease continue to progress.
  • The study is still recruiting patients, but they currently only have sites in the United Kingdom.


This early data shows that NVG-111 is generally well tolerated with a manageable safety profile. Though this was, first and foremost, a safety study, there was some preliminary evidence of efficacy. We look forward to seeing how this trial progresses in the future.

Links and Resources:

Watch the interview on the abstract here:

You can read the actual ASH abstract here: First-in-Human Phase I Trial of a ROR1 Targeting Bispecific T Cell Engager (NVG-111) in Combination with Ibrutinib or As Monotherapy in Subjects with Relapsed Refractory Chronic Lymphocytic Leukaemia (CLL) and Mantle Cell Lymphoma (MCL)

Take care of yourself first.

Ann Liu, PhD