Title
A Phase 2 Multicenter, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Oral NRC-2694-A in Combination with Paclitaxel in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Who Progressed on or After Immune Checkpoint Inhibitor Therapy

Description
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.

Objective
Primary Objective: 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

Secondary Objectives:
1) To evaluate the PFS, OS, DoR, and CBR of patients treated orally with NRC-2694-A in combination with paclitaxel
2) To evaluate the safety of NRC-2694-A in combination with paclitaxel
3) To characterize the PK of NRC-2694-A after repeated oral doses

Exploratory Objective: To determine the association between NRC-2694-A activity and biomarkers in blood samples

Treatment Experimental: NRC-2694-A In Combination with paclitaxel
Patients will receive NRC-2694-A 300 mg orally once daily and paclitaxel 175 mg/m² IV infusion over approximately 3 hours once in 21 days for 6 cycles or more.

Drug: NRC-2694-A
300 mg orally once daily

Drug: Paclitaxel
175 mg/m² IV infusion over approximately 3 hours

Key Eligibility Inclusion Criteria:

Is willing and capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.

Is male or female aged 18 years or older at the time of consent.

Has histologically confirmed unresectable R/M HNSCC (oral cavity, oropharynx, hypopharynx, and larynx).

Has documented radiographical progressive disease assessed by the principal investigator per RECIST v1.1.

Has a measurable lesion per RECIST v1.1.

Has ECOG performance status score of
Must have progressed during or after receiving ICI therapy, such as pembrolizumab or nivolumab. Patients with prior immune-mediated reactions due to ICI therapies (eg, pembrolizumab or nivolumab) and who had recovered prior to study entry will also be eligible.

Female patients of childbearing potential should have a negative urine test before enrollment. If the urine pregnancy test is positive or gives equivocal results, a serum pregnancy will be required for confirmation.

Patients of reproductive age must use acceptable methods of contraception throughout the study period and for 30 days following the last dose of investigational product (see protocol for further guidance).

During screening and at subsequent visits, the investigator should ensure adequate bone marrow reserve (neutrophil count >/=1500/mm3, platelet count >/=100,000/mm3, and hemoglobin level 8.0 g/dL), renal function (creatinine clearance >/=50 mL/min calculated by Cockcroft-Gault formula), liver function (total bilirubin level
Must have completed a duration of at least 4 weeks after stopping ICI therapy and must have recovered to grade

Applicable Disease Sites
Head and Neck

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital