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

NCT ID: NCT04763083

Last Updated: 2023-07-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-14
• Study Completion Date: 2025-12-31

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A: Haematological malignancies

Group Type: EXPERIMENTAL

NVG-111

Intervention Type: DRUG

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

Group B: Solid tumours

Group Type: EXPERIMENTAL

NVG-111

Intervention Type: DRUG

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

Interventions

NVG-111

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NovalGen Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Parag Jasani, MBBS, FRCP, FRCPath

Role: PRINCIPAL_INVESTIGATOR

Royal Free London NHS Foundation Trust and University College London Hospitals

Locations

University College London Hospital

London, , United Kingdom

Site Status: RECRUITING

Royal Marsden Hospital

London, , United Kingdom

Site Status: RECRUITING

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Amit C Nathwani, MBChB, FRCP, FRCPath, PhD

Role: CONTACT

a.nathwani@novalgen.co.uk

0044 207 139 8639

Facility Contacts

William Townsend

Role: primary

william.townsend@nhs.net

Juanita Lopez

Role: primary

Juanita.Lopez@icr.ac.uk

Fiona Thistlethwaite

Role: primary

fiona.thistlethwaite@nhs.net

Other Identifiers

2020-000820-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NVG111-101

Identifier Type: -

Identifier Source: org_study_id