NUC-3373 in Combination With Other Agents in Patients With Advanced Solid Tumours (NCT05714553) | Clinical Trial Compass
TerminatedPhase 1/2
NUC-3373 in Combination With Other Agents in Patients With Advanced Solid Tumours
Stopped: The NuTide:303 study was terminated at NuCana's discretion due to refinement of the pipeline strategy. The overall risk benefit assessment of NUC-3373 remains positive and future NUC-3373 studies are under consideration.
United Kingdom19 participantsStarted 2023-03-08
Plain-language summary
This study is an open-label, multi-arm, parallel cohort, dose validation and expansion design. The study is modular in design, allowing evaluation of the safety, efficacy and pharmacokinetics (PK) of NUC-3373 in combination with other agents for the treatment of patients with different tumour types.
Each module is designed to evaluate a different NUC-3373 combination and consists of a dose-validation phase (Phase Ib) and a dose-expansion phase (Phase II).
Phase Ib of each module will determine the safety and tolerability of the combinations for further clinical evaluation in Phase II. Approximately 6-20 evaluable patients will be enrolled in the Phase Ib stage of each module to determine safety, tolerability, and preliminary efficacy of NUC-3373 in combination with other agents. Each module will then move into Phase II to enable a further assessment of safety and efficacy in approximately 20-40 patients.
Module 1 will assess NUC-3373 + leucovorin (LV) in combination with pembrolizumab for the treatment of patients with advanced/metastatic solid tumours who have progressed on ≤2 prior therapies for metastatic disease, that may have included 1 prior immunotherapy-containing regimen (either monotherapy or in combination with chemotherapy) or who have not progressed but where addition of NUC-3373 + LV to standard pembrolizumab monotherapy may be appropriate (e.g., patients who could not tolerate post- immuno-oncology (IO) standard of care therapy).
Module 2 will assess NUC-3373 + LV in combination with docetaxel for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC) or pleural mesothelioma who have progressed on, or were unable to tolerate, 1 or 2 prior lines of cytotoxic chemotherapy-containing regimens for advanced/metastatic disease.
The opening of each module will be at the discretion of the Sponsor. Further modules may be added as non-clinical and clinical data become available to support additional NUC-3373 combinations and tumour types.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Provision of written informed consent.
✓. Confirmed diagnosis of one of the protocol-specified tumour types (refer to the relevant module for specific criteria).
✓. Age ≥18 years.
✓. Minimum life expectancy of ≥12 weeks.
✓. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.
✓. Measurable disease as defined by RECIST v1.1.
✓. Adequate bone marrow function as defined by absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥100×109/L (with no evidence of bleeding), and haemoglobin ≥9 g/dL.
✓. Adequate liver function (refer to the relevant module for specific criteria).
Exclusion criteria
✕. History of hypersensitivity or current contra-indications to 5-fluorouracil (5-FU), floxuridine (FUDR), capecitabine (refer to latest package inserts), or the components of the NUC-3373 drug product formulation (super refined polysorbate 80 \[SRP80\], dimethylacetamide \[DMA\]).
What they're measuring
1
Number of patients tolerating dose levels (maximum tolerated dose; MTD) in each of the combinations
Timeframe: Assessed from baseline to 30 days after last dose of study drug
2
Number of patients reporting treatment-emergent adverse events (TEAEs) in each of the combinations
Timeframe: Assessed from baseline to 30 days after last dose of study drug
3
Number of patients achieving a reduction in tumour volume (Objective response rate; ORR)
Timeframe: Assessed from baseline to 30 days after last dose of study drug
✕. Symptomatic central nervous system or leptomeningeal metastases.
✕. Symptomatic ascites, ascites currently requiring drainage procedures or ascites requiring drainage over the 3 months prior to date of first dose of study drug.
✕. Chemotherapy, hormonal therapy, radiotherapy (other than a short cycle of palliative radiotherapy, e.g., for bone pain\*), immunotherapy, biological agents, or exposure to another investigational agent within 21 days (or four times the half-life for molecular targeted agents, whichever is shorter) of first administration of study treatment:
✕. For nitrosoureas and mitomycin C within 6 weeks of first administration of NUC-3373
✕. Corticosteroid treatment is allowed during screening but should be weaned to a dose of 10 mg prednisolone (or steroid equivalent) by Cycle 1 Day 1 \* Palliative radiotherapy during participation in the study is permitted, but should not be concurrent with study treatment and recovery should be allowed to prevent overlapping toxicity. It should not include a target lesion.
✕. Residual toxicities from prior chemotherapy, immunotherapy or radiotherapy which have not regressed to Grade ≤1 severity (Common Terminology Criteria for Adverse Events (CTCAE) v5.0), except for alopecia, peripheral neuropathy and ototoxicity (which are excluded if ≥Grade 3).
✕. Uncontrolled concurrent cancer other than the indication under investigation. Patients with a concurrent cancer whose natural history or treatment does not have the potential to interfere with safety or efficacy assessment are eligible.