NCT04763083

First in Human Study of NVG-111 in Relapsed/Refractory ROR1+ Malignancies

An Open-label, Phase 1, First in Human Study Investigating the Safety, Tolerability, Pharmacokinetics and Efficacy of NVG-111 in Subjects With Relapsed/Refractory ROR1+ Malignancies

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: NovalGen Ltd. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

NVG-111 is a bispecific antibody drug, having two "arms", one arm attaches to a substance on cancer cells called ROR1, the other arm attaches to the body's immune cells directing them to kill the cancer cells. This is the first clinical trial of the drug NVG-111, and will include patients with certain types of cancer including chronic lymphocytic leukaemia (CLL), small lymphocytic lymphoma (SLL) mantle cell lymphoma (MCL), follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) in Group A. Subjects with solid tumours, focusing initially on stage IV non-small cell lung cancer (NSCLC) or malignant melanoma.

Detailed description

Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is a protein which is expressed at high levels on many types of cancers but is absent or expressed at low levels in normal adult organs. NVG-111 is a bispecific antibody T cell engager, comprising tandem single chain variable fragments (scFv), one arm binding to ROR1 on cancer cells, the other to cell surface CD3 on lymphocytes. Dual binding of NVG-111 causes MHC-independent immunological synapse formation, releasing perforins, granzyme B and cytokines, resulting in targeted killing of the cancer cells. This is a Phase 1 first in human study to assess the safety, pharmacokinetics and efficacy of NVG-111 in patients with subjects with relapsed/refractory ROR1+ malignancies. A range of doses will be studied in sequential cohorts to understand safety, pharmacokinetics and pharmacodynamics of the drug and establish the recommended phase 2 dose (RP2D). At each dose level, patients will receive 3 cycles of NVG-111 by continuous intravenous infusion, each cycle consists of 21 days treatment. Additional cycles may be given depending on the response seen. All patients will have a safety follow up visit 4 weeks after completion of treatment with NVG-111, and will then enter long term follow up for up to two years to evaluate the duration of efficacy.

Conditions

• Chronic Lymphocytic Leukaemia
• Small Lymphocytic Lymphoma
• Mantle Cell Lymphoma
• Follicular Lymphoma
• Diffuse Large B Cell Lymphoma
• Non-small Cell Lung Cancer (NSCLC)
• Malignant Melanoma

Interventions

Type	Name	Description
DRUG	NVG-111	Open label, continuous iv infusion, escalating doses of NVG-111 for minimum 3 cycles

Timeline

• Start date: 2021-05-14
• Primary completion: 2023-12-01
• Completion: 2025-12-01
• First posted: 2021-02-21
• Last updated: 2023-07-07

Locations

3 sites across 1 country: United Kingdom