FID-007 and Cetuximab in Treating Patients With Advanced Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

1. Ability to understand and willingness to provide informed consent before the startof any study-specific procedures.

2. Age ≥18 years old.

3. A diagnosis of recurrent or metastatic HNSCC at 1 of the following sites:

4. Nasal/paranasal sinuses

5. Nasopharynx (Epstein-Barr virus [EBV] negative only)

6. Oral cavity

7. Oropharynx

8. Hypopharynx

9. Larynx

10. Disease progression after treatment with PD-L1-based immune checkpoint inhibitor atany time. This can be as monotherapy or in combination with chemotherapy.

11. Measurable disease according to RECIST version 1.1.

12. Adequate treatment washout period of ≥21 days or 5 half-lives, whichever is shorter,for prior chemotherapy, radiotherapy, hormonal therapy, biological therapy, orimmunotherapy before the first dose of study drug administration. Note: Palliativeradiation is permitted but not ≤7 days before the first dose of study drug.

13. ECOG PS of 0 or 1.

14. Recovery from any toxic effects of previous chemotherapy, targeted therapy, orradiotherapy as judged by the investigator to Grade ≤1 (except for alopecia)according to NCI CTCAE version 5.0.

15. Adequate bone marrow and organ function defined as the following: Bone marrow function

• Absolute neutrophil count ≥1500/mm3 (growth factor administration is notpermitted ≤1 week before the screening assessment)

• Platelet count ≥100,000/mm3 (platelet transfusion is not permitted ≤1 weekbefore the screening assessment)

• Hemoglobin ≥8 g/dL (criteria must be met without packed red blood celltransfusion ≤1 week before the screening assessment; chronic treatment witherythropoietin is permitted if the patient is on erythropoietin for ≥8 weeks) Blood clotting function

• International normalized ratio (INR) ≤1.5 × upper limit of normal (ULN) andactivated partial thromboplastin time ≤1.5 × ULN (except patients who are receivingtherapeutic anticoagulation and whose INR should be within the therapeutic range) Renal function

•Calculated clearance (using the Cockroft-Gault formula) ≥40 mL/min/1.73 m2. Actualbody weight should be used for calculating creatinine clearance. For patients with abody mass index >30 kg/m2, lean body weight should be used instead Hepatic function

• Total bilirubin ≤1.5 × ULN (patients with Gilbert's disease can have bilirubin >1.5 × ULN to <3 × ULN)

• Aspartate aminotransferase/alanine aminotransferase ≤3 × ULN

10. An estimated life expectancy of at least 3 months based on investigator judgment.

11. Negative serum pregnancy test result at screening for female patients ofchildbearing potential.

12. Willingness to abide by the contraceptive requirements in Appendix 1 of theprotocol.

Exclusion Criteria:

1. Known hypersensitivity to paclitaxel.

2. EBV-positive nasopharyngeal cancer, sinonasal undifferentiated carcinoma,esthesioneuroblastoma, or squamous cell carcinoma of the salivary gland or skin,based on the patient's medical history.

3. Received >1 prior line of anticancer therapy for recurrent or metastatic HNSCC. Allpatients must be previously treated with an immune checkpoint inhibitor either asmonotherapy or in combination with chemotherapy. Patients treated with upfrontcombination chemo-immunotherapy followed by immunotherapy maintenance are consideredto have received only 1 prior line of therapy. Chemotherapy given as part oftreatment for locally advanced disease in the adjuvant or neoadjuvant setting is notconsidered a line of prior therapy for recurrent/metastatic disease. If the patientreceived prior treatment with Cetuximab, paclitaxel, or nab-paclitaxel incombination with radiation in the locally advanced setting and no relapse within 6months of treatment discontinuation, enrollment is permitted if the treatingphysician believes that retreatment with Cetuximab or a taxane is a clinicallyreasonable option. However, patients who received these agents for recurrent ormetastatic disease will be excluded.

4. Serious medical risk factors involving any of the major organ systems, or seriouspsychiatric disorders, that in the judgment of the investigator could compromise thepatient's safety or the study data integrity.

5. Preexisting sensory neuropathy of Grade >1 severity by NCI CTCAE version 5.0criteria.

6. Known history of uncontrolled HIV infection defined as CD4+ cells <350/mm3.

7. Requirement of systemic steroids at daily doses >10 mg prednisone equivalentsystemic exposure daily, including for control of symptoms.

8. Use of any CYP2C8 and CYP3A4 inhibitor (eg, ketoconazole and other imidazoleantifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir,saquinavir, indinavir, and nelfinavir) or inducer (eg, rifampicin, carbamazepine,phenytoin, efavirenz, and nevirapine) in the previous 14 days before the first doseof study drug until the last PK sample is obtained in the study.

9. Known brain metastasis. Note: Patients whose central nervous system metastases havebeen treated by surgery or radiotherapy, who are no longer on corticosteroids, andwho are neurologically stable are eligible.

10. Current or recent participation in a study of an investigational product in theprior 4 weeks. Note: Patients who have completed the treatment phase of aninvestigational study and have entered the follow-up phase of the investigationalstudy may participate in FID-007-003 as long as it has been ≥4 weeks before thefirst dose of study drug.

11. Pregnancy, breastfeeding, or plans to become pregnant during the study or within 24weeks after the last dose of study drug (Appendix 1 of the protocol).

12. Plans to donate/bank or retrieve eggs (ova, oocytes) during the study or within 24weeks after the last dose of study drug (Appendix 1 of the protocol).