Solid tumours Cancer
Conditions
Interventions
The dose escalation phase (Phase I) will consist of two parts. In Part I, NVG-222 will be administered in single participant cohorts. These participants will follow accelerated dose escalation, with i
Phase IIa), participants will receive NVG-222 as an intravenous infusion at a dose and schedule that will be determined based on data from the dose escalation phase.
All participants may receive NVG-2
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Written (signed and dated) informed consent and capable of co-operating with investigational medicinal product (IMP) administration and follow-up. 2. Histologically or cytologically proven advanced solid tumours (including non-small cell lung cancer, triple-negative breast cancer, malignant melanoma, ovarian cancer, and other solid tumour types where there is supportive ROR1 expression data), refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the patient. 3. Objectively evaluable or measurable disease, according to RECIST V1.1. 4. Consent to access and analyse suitable archival sample or consent for fresh tumour biopsy at baseline (if no suitable archival sample is available). 5. Life expectancy of at least 12 weeks. 6. Eastern Cooperative Oncology Group performance status of 0–1. 7. Haematological and biochemical indices within prescribed ranges. These measurements should be performed to confirm the patient’s eligibility to participate in the trial. 8. Aged 18 years or over at the time consent is given.
Exclusion criteria
Exclusion criteria: 1. Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy or other investigational medicinal products (IMPs) during the previous 28 days before the first dose of IMP (or last dose of an immunotherapy during the previous 12 weeks). 2. Therapeutic antibodies (for any indication), within 28 days prior to first NVG-222 administration. 3. Ongoing toxic manifestations of previous treatments greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (other than alopecia of any grade or Grade 2 peripheral neuropathy) with certain exceptions permitted as per protocol. 4. Any central nervous system metastases (unless patients had local therapy and are asymptomatic AND radiologically stable AND have been off steroids for the last 28 days prior to screening). 5. History or presence of dementia or psychosis. Patients with a previous history of epilepsy may participate if it is controlled with medication. Patients who have made a good recovery from a stroke, and who have no residual cognitive impairment and minimal or no motor or sensory loss, may participate if the neurological insult occurred >1 year prior to screening with no further recurrence. 6. Women who are pregnant or breastfeeding (or planning to breastfeed). 7. Women of childbearing potential. However, those patients who are not already pregnant or breastfeeding (or planning to breastfeed) are eligible, provided they have a negative highly sensitive serum pregnancy test within 7 days before enrolment and agree to follow the trial’s contraceptive requirements. 8. Male patients with partners of childbearing potential. However, those patients who agree to follow the trial’s contraceptive guidance are eligible. 9. Major surgery from which the patient has not yet recovered. 10. Concomitant steroids. The use of corticosteroids at a dose =10 mg/day prednisone or equivalent is permitted; however, there must be documentation that the patient was on a stable dose of at least 7 days duration prior to trial enrolment. Inhaled and topical steroids are permitted. 11. At high medical risk because of non-malignant systemic disease, including active, uncontrolled infection. 12. Known to be serologically positive for hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV). 12.1. Active hepatitis B infection. Patients with negative serologic or PCR test results for acute or chronic HBV infection are eligible. 12.2. Active hepatitis C infection. Patients who test positive for hepatitis C antibody with a detectable HCV load are not eligible. 12.3. Patients with known HIV are excluded unless viral load is undetectable and CD4 count is above 350 cells/mm3 on stable Highly Active Antiretroviral Therapy. 13. Known or suspected hypersensitivity reaction to previous biological therapy or any of the NVG-222 excipients that, in the opinion of the Investigator, is a contraindication for participation in this study. 14. Patient is unable to receive at least 1 of the following prophylactic medications for tumour lysis syndrome: allopurinol, febuxostat or rasburicase. 15. Significant cardiovascular disease, as defined within the protocol. 16. Clinically significant lung disease, as defined within the protocol. 17. Participating in or plans to participate in another interventional clinical trial whilst taking part in this Phase I/IIa trial of NVG-222. Certain exceptions are permitted as per protocol. 18. Current or prior malignancy that could affect saf
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Nature and frequency of dose-limiting toxicities (DLTs). DLTs are defined and assessed according to specific criteria in the trial protocol. Evaluation of this endpoint will occur when sufficient participants have completed the DLT assessment period (first 28 days of administration) and all relevant data have been collected. 2. Determination of the maximum tolerated dose (MTD) and/or optimal biological dose (OBD) and/or therapeutic dose range and/or optimal dose schedule for NVG-222. The Bayesian optimal interval model will recommend the NVG-222 dose with an estimated DLT rate within the target range of 20% to 33%. In the absence of DLT, the single agent recommended Phase II dose or OBD and schedule will be determined based upon the maximum administered dose and all available safety, pharmacokinetic (PK) and pharmacodynamic data. Evaluation of this endpoint will occur when sufficient participants have completed the DLT assessment period (first 28 days of administration) and all clinically relevant data have been reviewed by the Sponsor, Chief Investigator and Principal Investigators. 3. Frequency of adverse events (AEs) considered at least possibly related to NVG-222 and number of Grade 3, 4 and 5 AEs considered at least possibly related to NVG-222. AEs, including relatedness, seriousness and severity (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5.0 with the exception of cytokine release syndrome [CRS] and neurotoxicity [ICANS], which will be graded according to American Society for Transplantation and Cellular Therapy [ASTCT] consensus grading) will be assessed by the Investigator. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. PK parameters of NVG-222, including minimum concentration (Cmin), maximum concentration (Cmax), area under the curve (AUC), clearance (CL), volume of distribution (Vd) and terminal elimination half-life (t1/2), in blood (serum) for intravenous administration, measured using a standard ligand binding assay. Additional PK parameters may be determined as appropriate. Samples for PK analysis will be taken at up to 30 timepoints for each participant over the duration of the trial. 2. Objective response rate, defined as the proportion of participants who achieve complete response (CR) or partial response (PR) as the best overall response according to RECIST V1.1. This endpoint will be evaluated at end of trial (EoT). 3. Disease control rate, defined as the percentage of participants who achieve CR, PR or a minimum of stable disease for 12 weeks based on Response Evaluation Criteria in Solid Tumours (RECIST) V1.1. This endpoint will be evaluated at EoT. 4. Duration of response, defined as the time from the initial occurrence of a documented PR or CR until documented disease progression or death due to any cause, whichever occurs first, according to RECIST V1.1. This endpoint will be evaluated at EoT. 5. Progression-free survival, defined as the time from the date of administration of the first dose of NVG-222 on this trial to disease progression or death from any cause or the date of censoring at the last time the participant was known to be progression free. Participants who start a new anti-cancer treatment will not be censored. This endpoint will be evaluated at EoT. 6. Overall survival, defined as the time from the date of administration of the first dose of NVG-222 on this trial to the date of death due to any cause, or to the date of censoring at the last time the participant was known to be alive. Participants who are lost to follow-up will be censored at the time of last contact; participants who start a new anti-cancer treatment will not be censored. This endpo | — |
Countries
England, United Kingdom
Contacts
Public ContactStuart;Jenny Smith;King
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Outcome results
None listed