Chronic Lymphocytic LeukaemiaPhase 1NCT04763083
First in Human Study of NVG-111 in Relapsed/Refractory ROR1+ Malignancies
A Phase 1 study testing NVG-111 in people with Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma, run by NovalGen Ltd. at 3 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukaemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma
- What is being tested?
- NVG-111
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 14 May 2021to Dec 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites, 3 recruiting
- Recruiting
University College London Hospital
London, W1T 7HA
William Townsend, william.townsend@nhs.net
Heather Shaw
- Recruiting
Royal Marsden Hospital
London
Juanita Lopez, Juanita.Lopez@icr.ac.uk
- Recruiting
The Christie NHS Foundation Trust
Manchester
Fiona Thistlethwaite, fiona.thistlethwaite@nhs.net
About this study
Official title: 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
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.
Read the 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)
- Being tested
- NVG-111
- Keywords
- ROR1 positive cancers, Bispecific T cell engagers
- Medical subject headings
- Leukemia, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Carcinoma, Non-Small-Cell Lung, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NVG-111Drug
Open label, continuous iv infusion, escalating doses of NVG-111 for minimum 3 cycles
| Study group | Role | What they receive |
|---|---|---|
| Group A: Haematological malignancies | Experimental | Not described Receives: Drug: NVG-111 |
| Group B: Solid tumours | Experimental | Not described Receives: Drug: NVG-111 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of treatment-emergent adverse events (TEAEs)
Safety parameter assessed by: type, frequency, severity and treatment-relatedness of AEs following commencement of dosing
Measured: 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
Measured: Up to 10 months
Number of adverse events of special interest (AESI)
Safety parameter: specific protocol-defined AEs of Grade >=3
Measured: Up to 10 months
Number of dose limiting toxicities (DLTs)
Safety parameter assessed by protocol-defined adverse events
Measured: Up to 28 days
Laboratory safety abnormalities
Safety parameter assessed by absolute values and change from baseline in laboratory safety assessments
Measured: Up to 10 months
Vital sign abnormalities
Safety parameter assessed by absolute values and change from baseline in vital signs
Measured: Up to 10 months
ECG abnormalities
Safety parameter assessed by absolute value and change from baseline in ECG intervals including QTcF
Measured: Up to 10 months
Changes from baseline in ECOG
Safety parameter assessed by change from baseline in ECOG performance status
Measured: Up to 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start14 May 2021
- Primary completionDec 2023 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NovalGen Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Parag Jasani, MBBS, FRCP, FRCPath, Principal investigator, Royal Free London NHS Foundation Trust and University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04763083
- Sponsor's protocol ID
- NVG111-101
- Other IDs
- 2020-000820-20
- Status last verified
- Sep 2022
- First submitted
- 12 Feb 2021
- Last updated
- 7 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The company is developing an IPD sharing plan which will be completed and posted prior to primary completion date of the study
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04763083
- Acronym / sponsor ID
- NVG111-101
- Conditions
- Chronic Lymphocytic Leukaemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Diffuse Large B Cell Lymphoma, Non-small Cell Lung Cancer (NSCLC)
- Keywords
- ROR1 positive cancers, Bispecific T cell engagers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- NovalGen Ltd.Industry (pharma, biotech, devices)
- Study start
- 14 May 2021 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: Haematological malignancies | Experimental | Drug: NVG-111 |
| Group B: Solid tumours | Experimental | Drug: NVG-111 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Personally signed informed consent document.
- Male or female, age ≥18 years.
- Relapsed or refractory ROR1+ malignancies
- ECOG performance status ≤2.
- Adequate organ function.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NVG-111Open label, continuous iv infusion, escalating doses of NVG-111 for minimum 3 cycles | Drug | Group A: Haematological malignancies, Group B: Solid tumours |
Primary outcome
Number of treatment-emergent adverse events (TEAEs)
Time frame: Up to 10 months
Safety parameter assessed by: type, frequency, severity and treatment-relatedness of AEs following commencement of dosing
Number of serious adverse events (SAEs)
Time frame: Up to 10 months
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
Number of adverse events of special interest (AESI)
Time frame: Up to 10 months
Safety parameter: specific protocol-defined AEs of Grade >=3
Number of dose limiting toxicities (DLTs)
Time frame: Up to 28 days
Safety parameter assessed by protocol-defined adverse events
Laboratory safety abnormalities
Time frame: Up to 10 months
Safety parameter assessed by absolute values and change from baseline in laboratory safety assessments
Vital sign abnormalities
Time frame: Up to 10 months
Safety parameter assessed by absolute values and change from baseline in vital signs
ECG abnormalities
Time frame: Up to 10 months
Safety parameter assessed by absolute value and change from baseline in ECG intervals including QTcF
Changes from baseline in ECOG
Time frame: Up to 10 months
Safety parameter assessed by change from baseline in ECOG performance status
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2023.
- Individual participant dataSharing planned: Undecided. The company is developing an IPD sharing plan which will be completed and posted prior to primary completion date of the study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parag Jasani, MBBS, FRCP, FRCPath principal investigator
Royal Free London NHS Foundation Trust and University College London Hospitals
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NVG-111 in people with Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma, run by NovalGen Ltd. at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Amit C Nathwani, MBChB, FRCP, FRCPath, PhD (0044 207 139 8639, a.nathwani@novalgen.co.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of treatment-emergent adverse events (TEAEs) (time frame: Up to 10 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2023.