A Phase I/IIa trial of NVG-222 in participants with solid tumours

Approved 19/01/2026, London - Chelsea Research Ethics Committee (Research Ethics Committee (REC) London Centre, 2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 1048 088; chelsea.rec@hra.nhs.uk), ref: 25/LO/0829

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.

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 endpoint will be evaluated at EoT.