This is a Phase 2, open-label, multicenter, single-arm study of NRC-2694-A in combination with paclitaxel in patients with R/M HNSCC with progression on or after ICI therapy. A total of approximately 46 male and female patients will be enrolled. This sample size is based on Simon's 2-stage design with historical control ORR of 30% and a target ORR of 50%.
Patients with recurrent and/or metastatic unresectable Head and Neck Cancer have a poor prognosis and limited treatment options. Pembrolizumab and Nivolumab, both ICIs (Immune Checkpoint Inhibitors), are approved therapies for this condition. However, no approved treatment options exist for patients who progress on ICI therapies. Hence, there is an unmet medical need post-failure of ICI therapy. NRC-2694-A is an orally administered small-molecule tyrosine kinase inhibitor. It was discovered and developed by NATCO Pharma Ltd. NRC-2694-A demonstrated response in HNSCC patients in a Phase-I study as a monotherapy. This was further substantiated in a Phase-II study in combination with cisplatin/carboplatin and paclitaxel.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
300 mg orally once daily
175 mg/m² IV infusion over approximately 3 hours
Providence Medical Foundation -Fullerton
Fullerton, California, United States
COMPLETEDLos Angeles Hematology Oncology Medical Group
Los Angeles, California, United States
COMPLETEDLynn Cancer Center
Boca Raton, Florida, United States
COMPLETEDMiami Cancer Center
Miami, Florida, United States
COMPLETEDNorton Cancer Institute - Downtown
Louisville, Kentucky, United States
COMPLETEDUniversity of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States
COMPLETEDWashington University - Siteman Cancer Center
St Louis, Missouri, United States
COMPLETEDDartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
COMPLETEDSalib Oncology
Easton, Pennsylvania, United States
COMPLETEDUniversity of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
COMPLETED...and 3 more locations
To determine if NRC-2694-A administered orally in combination with paclitaxel demonstrates objective response in patients with R/M HNSCC, who have had radiological progression on or after treatment with ICI therapies like pembrolizumab or nivolumab
Objective response in terms of CR/PR per RECIST v1.1
Time frame: Baseline through approximately up to 24 weeks
Progression-free survival
defined as the interval of time between the date of enrollment to the earliest date of disease progression, as determined by local radiologic assessment per RECIST v1.1, or death due to any cause, whichever occurs first
Time frame: Baseline through approximately up to 24 weeks
Overall survival
defined as the time from the date of enrollment to the date of death due to any cause
Time frame: Baseline through approximately up to 24 weeks
Duration of response
defined as the time from first confirmed objective response to disease progression
Time frame: Baseline through approximately up to 24 weeks
Clinical benefit response
defined as CR + PR + SD for ≥ 6 months
Time frame: Baseline through approximately up to 26 weeks
Number of adverse events
Time frame: Baseline through approximately up to 24 weeks
Number of participants with abnormal physical examination findings
Symptom-directed physical examination will be conducted to evaluate skin rash, diarrhea, paresthesia, and dyspnea graded according to NCI CTCAE version 5.0.
Time frame: Baseline through approximately up to 24 weeks
Number of participants with abnormal vital signs
Clinically significant abnormal blood pressure, heart rate, respiratory rate, and oral body temperature graded according to NCI CTCAE version 5.0.
Time frame: Baseline through approximately up to 24 weeks
Assessing safety through ECOG (Eastern Cooperative Oncology Group)
The severity of the AE will be graded according to the NCI CTCAE version 5.0 (NCI Common Terminology Criteria for Adverse Events. The CTCAE displays Grades 1 through Grade 5 with the higher score as worse outcome)
Time frame: Baseline through approximately up to 24 weeks
Number of participants with abnormal clinical laboratory tests results
Clinically significant abnormal hematology, biochemistry, coagulation and urinalysis test results graded according to NCI CTCAE version 5.0.
Time frame: Baseline through approximately up to 24 weeks
Number of participants with abnormal ECGs (Electrocardiograms)
Clinically significant abnormal ECG findings will be graded per NCI CTCAE version 5.0.
Time frame: Baseline through approximately up to 24 weeks
Plasma PK parameters of NRC-2694-A measured via Cmax (Maximum plasma concentration)
Time frame: Baseline through approximately up to 24 weeks
Plasma PK parameters of NRC-2694-A measured via Tmax (time to reach the maximum plasma concentration)
Time frame: Baseline through approximately up to 24 weeks
Plasma PK parameters of NRC-2694-A measured via Ctrough (observed trough plasma concentration at the dosing interval tau)
Time frame: Baseline through approximately up to 24 weeks
Plasma PK parameters of NRC-2694-A measured via AUC0-t (area under the concentration-time curve from time zero to the time of last measurable concentration)
Time frame: Baseline through approximately up to 24 weeks
Plasma PK parameters of NRC-2694-A measured via AUC0-τ (area under the concentration-time curve from time zero to the dosing interval tau)
Time frame: Baseline through approximately up to 24 weeks
Plasma PK parameters of NRC-2694-A measured via CL/F (apparent clearance)
Time frame: Baseline through approximately up to 24 weeks
Plasma PK parameters of NRC-2694-A measured via Vz/F (apparent volume of distribution)
Time frame: Baseline through approximately up to 24 weeks
Plasma PK parameters of NRC-2694-A measured via Rac Cmax (accumulation ratio based on maximum plasma concentration)
Time frame: Baseline through approximately up to 24 weeks
Plasma PK parameters of NRC-2694-A measured via Rac AUC (accumulation ratio based on area under the concentration-time curve)
Time frame: Baseline through approximately up to 24 weeks
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