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

Inclusion Criteria:

• Is willing and capable of understanding the written informed consent, providessigned and witnessed written informed consent, and agrees to comply with protocolrequirements.

• 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 progressive disease assessed by the principal investigator accordingto RECIST v1.1.

• Has a measurable lesion per RECIST v1.1.

• Has ECOG performance status score of ≤2.

• Must have progressed during or after receiving ICI therapy, such as pembrolizumab ornivolumab. Patients with prior immune-mediated reactions due to ICI therapies (eg,pembrolizumab or nivolumab) and who had recovered prior to study entry will also beeligible.

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

• Patients of reproductive age must use acceptable methods of contraception throughoutthe 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 adequatebone marrow reserve (neutrophil count ≥1500/mm3, platelet count ≥100,000/mm3, andhemoglobin level 8.0 g/dL), renal function (creatinine clearance ≥30 mL/mincalculated by Cockcroft-Gault formula), liver function (total bilirubin level ≤1.5 ×ULN [except patients with documented Gilbert's syndrome] and serum transaminaselevels ≤2.5 × ULN or ≤5 × ULN for liver metastasis and/or obstructive jaundice).

• Must have completed a duration of at least two weeks after stopping ICItherapy/investigational therapy/salvage therapy and must have recovered to grade ≤1from all toxicities due to such therapies.

Exclusion Criteria:

• Has cardiac, hepatic, endocrine, pulmonary, or autoimmune disease, interstitial lungdisease, renal or psychiatric disorders, not controlled with therapy correspondingto the illness or a condition that contraindicates the use of a taxane or an EGFRinhibitor.

• Has Cirrhosis of liver at a level of Child-Pugh B (or worse).

• Has uncontrolled brain metastases. Patients are allowed if brain metastasis has beenpreviously treated with surgery, whole brain irradiation, and/or stereotacticradiosurgery and are considered controlled (controlled by the dose ≤10 mg/day ofprednisone or equivalent) at the time of the first dose of investigational product.Radiological evaluation of brain metastasis will be performed only if the patienthas symptoms. For asymptomatic patients, brain imaging during screening is notrequired.

• Has baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTcinterval >480 milliseconds [CTCAE Grade 1] using Fredericia's QT correctionformula).

• Has a history of additional risk factors for Torsade de pointes (eg, heart failure,hypokalemia, family history of long QT syndrome).

• Has had prior cetuximab therapy for recurrent or metastatic disease. Note thatcetuximab used concomitantly with radiotherapy or as an induction therapy isacceptable

• Has received any other EGFR-targeted therapies for recurrent or metastatic disease.

• Currently participating in any clinical trial or receiving investigational therapyon expanded access or compassionate basis.

• Has nasopharyngeal carcinomas or salivary gland cancers.

• Female patient who tested positive for pregnancy.

• Female patient who is breastfeeding or planning to become pregnant, or male patientplanning to father a child within the duration of the study.

• Has tested positive for HIV, HBsAg, HCV antibody, or HCV RNA at screening. However,patients who test positive for HCV antibody, but negative for HCV RNA, will beallowed. In addition, patients with controlled HIV, chronic HBV on suppressiveantiviral therapy, or a history of HCV infection status post-curative antiviraltreatment with an HCV viral load below limit of quantification are permitted toparticipate (DHHS 2020).

• Has active infection requiring intravenous anti-infective therapy within 7 daysprior to Day 1 Cycle 1 or is febrile due to infection.

• Has had major surgery within 4 weeks prior to screening.

• Administered a live attenuated vaccine within 4 weeks prior to Day 1 Cycle 1 oranticipation that such a live attenuated vaccine will be required during the study.

• Has known or suspected hypersensitivity to any components of the formulation usedfor this investigational product.

• Has concurrent disease or any clinically significant abnormality following theinvestigator's review of the screening physical examination findings, 12-lead ECGresults, and clinical laboratory tests, which in the judgment of the investigatorwould interfere with the patient's participation in this study or evaluation ofstudy results.

• Unable to come for study visits per schedule.

• Has current drug or alcohol abuse.

• Has received prior treatment with paclitaxel or docetaxel or any other drugs withtaxane like mode of action for recurrent or metastatic or recurrent HNSCC. However,prior paclitaxel or docetaxel or any other drugs with taxane like mode of action asa component of a curatively-intended multimodality treatment for locally advancedHNSCC is permitted.