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

NVG-111

Amit C Nathwani, MBChB, FRCP, FRCPath, PhD

William Townsend

Heather Shaw

Martin Forster

Juanita Lopez

Fiona Thistlethwaite

Parag Jasani, MBBS, FRCP, FRCPath

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.

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.

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

The company is developing an IPD sharing plan which will be completed and posted prior to primary completion date of the study

Safety parameter assessed by: type, frequency, severity and treatment-relatedness of AEs following commencement of dosing

Safety parameter defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent disability/incapacity, is a congenital anomaly/birth defect, or is medically significant/important

Safety parameter: specific protocol-defined AEs of Grade \>=3

Safety parameter assessed by protocol-defined adverse events

Safety parameter assessed by absolute values and change from baseline in laboratory safety assessments

Safety parameter assessed by absolute values and change from baseline in vital signs

Safety parameter assessed by absolute value and change from baseline in ECG intervals including QTcF

Safety parameter assessed by change from baseline in ECOG performance status

NovalGen Ltd.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
First in Human Study of NVG-111 in Relapsed/Refractory ROR1+ Malignancies	NCT04763083	Chronic Lymphoc... Small Lymphocyt... Mantle Cell Lym... Follicular Lymp... Diffuse Large B... Non-small Cell ... Malignant Melan...	NVG-111	18 Years -	NovalGen Ltd.
First in Human Study of NVG-111 in Relapsed/Refractory ROR1+ Malignancies	NCT04763083	Chronic Lymphoc... Small Lymphocyt... Mantle Cell Lym... Follicular Lymp... Diffuse Large B... Non-small Cell ... Malignant Melan...	NVG-111	18 Years -	NovalGen Ltd.

Spots Global Cancer Trial Database for bispecific t cell engagers