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

NCT04763083 | Unknown Phase 1 DMC

• 2 other identifiers: NVG111-1012020-000820-20
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief 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.

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

Keywords

ROR1 positive cancers; Bispecific T cell engagers

Outcome Measures

Primary Outcomes (8)

• Number of treatment-emergent adverse events (TEAEs)

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

  Up to 10 months

• Number of serious adverse events (SAEs)

  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

  Up to 10 months

• Number of adverse events of special interest (AESI)

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

  Up to 10 months

• Number of dose limiting toxicities (DLTs)

  Safety parameter assessed by protocol-defined adverse events

  Up to 28 days

• Laboratory safety abnormalities

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

  Up to 10 months

• Vital sign abnormalities

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

  Up to 10 months

• ECG abnormalities

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

  Up to 10 months

• Changes from baseline in ECOG

  Safety parameter assessed by change from baseline in ECOG performance status

  Up to 10 months

Study Arms (2)

Group A: Haematological malignancies

EXPERIMENTAL

Drug: NVG-111

Group B: Solid tumours

EXPERIMENTAL

Drug: NVG-111

Interventions

NVG-111 DRUG

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

Group A: Haematological malignancies; Group B: Solid tumours

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Personally signed informed consent document.
• Male or female, age ≥18 years.
• Relapsed or refractory ROR1+ malignancies
• ECOG performance status ≤2.
• Adequate organ function.
• Bilirubin ≤1.5 x ULN (unless Gilbert's syndrome).
• AST and ALT ≤2.5 x ULN (if no hepatic CLL or MCL), or AST and ALT ≤5 x ULN (if hepatic CLL or MCL).
• APTT and PT ≤1.5 x ULN.
• ANC ≥0.5 x 10\^9 /L (without growth factors) and platelets ≥ 30 x 10\^9 /L (without transfusion).
• Serum creatinine ≤2 x ULN.
• Estimated creatinine clearance ≥30 mL/min.
• In females of childbearing potential, a negative serum pregnancy test.
• For both males and females, willingness to use adequate contraception.
• Willingness and ability to comply with study procedures.

You may not qualify if:

• Richter's transformation.
• CNS or leptomeningeal active disease.
• High tumour bulk as defined in the protocol.
• Allogeneic or autologous organ transplant within prior 6 months.
• Uncontrolled autoimmune haemolytic anaemia or idiopathic thrombocytopenic purpura within 8 weeks of screening.
• Clinically significant neurological disease.
• Clinically significant cardiovascular disease or ECG abnormalities.
• Severe chronic lung disease.
• Positive test at Screening for HIV, hepatitis B or hepatitis C infection.
• Any other concurrent cancer or cancer treatments.
• Uncontrolled ongoing infection
• Recent major surgery
• Concurrent participation in another clinical trial, or experimental therapy within 5 half-lives of Screening
• Pregnant or currently breastfeeding.
• Any other medical condition that in the opinion of the investigator contraindicates participation in the study.

Sponsors & Collaborators

• NovalGen Ltd.: lead

Study Sites (3)

University College London Hospital

London, W1T 7HA, United Kingdom

RECRUITING

Royal Marsden Hospital

London, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

MeSH Terms

Conditions

Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Carcinoma, Non-Small-Cell Lung; Melanoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Parag Jasani, MBBS, FRCP, FRCPath

  Royal Free London NHS Foundation Trust and University College London Hospitals

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amit C Nathwani, MBChB, FRCP, FRCPath, PhD

CONTACT

0044 207 139 8639; a.nathwani@novalgen.co.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 21, 2021
• Study Start: May 14, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2025
• Last Updated: July 7, 2023

Record last verified: 2022-09

Locations

GB (3)