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

The goal of this FID-007 Clinical Trial is to compare the efficacy of different dosing regimens of FID-007 in combination with Cetuximab in patients with recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC). The main questions it aims to answer are: to evaluate the efficacy, and to characterize the safety and tolerability. Eligible participants will be enrolled and randomized to 1 of 2 arms of FID-007 with fixed-dose Cetuximab in each 28-day cycle.

The goal of this FID-007 Randomized, Multicenter, Open-label clinical trial is to compare the efficacy of different dosing regimens of FID-007 in combination with Cetuximab in patients with recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) based on objective response rate. The main questions it aims to answer are:

* To evaluate the efficacy of different dosing regimens of FID-007 in combination with Cetuximab in patients based on Best Overall Response (BOR), Duration of Response (DoR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS).
* To characterize the pharmacokinetics (PK) of FID-007 and its metabolites (6-α-hydroxypaclitaxel and 3'-p-hydroxypaclitaxel) following administration of different dosing regimens of FID-007 in combination with Cetuximab in patients with recurrent or metastatic HNSCC.
* To characterize the safety and tolerability of different dosing regimens of FID-007 in combination with Cetuximab in patients.

Eligible participants will be enrolled and randomized to 1 of 2 arms of FID-007 with fixed-dose Cetuximab (starting from Cycle 2, 500 mg/m2 intravenous \[IV\] infusion every 2 weeks on Days 1 and 15 of each 28-day cycle). Patients will receive FID-007 via IV infusion over 30 minutes at their assigned dose on Days 1, 8, and 15 of each 28-day cycle.

Patients will continue to receive Cetuximab and FID-007 until they meet the study drug discontinuation criteria.

Eligibility Criteria:
Inclusion Criteria:

1. Ability to understand and willingness to provide informed consent before the start of any study-specific procedures.
2. Age ≥18 years old.
3. A diagnosis of recurrent or metastatic HNSCC at 1 of the following sites:

   1. Nasal/paranasal sinuses
   2. Nasopharynx (Epstein-Barr virus \[EBV\] negative only)
   3. Oral cavity
   4. Oropharynx
   5. Hypopharynx
   6. Larynx
4. Disease progression after treatment with PD-L1-based immune checkpoint inhibitor at any time. This can be as monotherapy or in combination with chemotherapy.
5. Measurable disease according to RECIST version 1.1.
6. Adequate treatment washout period of ≥21 days or 5 half-lives, whichever is shorter, for prior chemotherapy, radiotherapy, hormonal therapy, biological therapy, or immunotherapy before the first dose of study drug administration. Note: Palliative radiation is permitted but not ≤7 days before the first dose of study drug.
7. ECOG PS of 0 or 1.
8. Recovery from any toxic effects of previous chemotherapy, targeted therapy, or radiotherapy as judged by the investigator to Grade ≤1 (except for alopecia) according to NCI CTCAE version 5.0.
9. Adequate bone marrow and organ function defined as the following:

   Bone marrow function
   * Absolute neutrophil count ≥1500/mm3 (growth factor administration is not permitted ≤1 week before the screening assessment)
   * Platelet count ≥100,000/mm3 (platelet transfusion is not permitted ≤1 week before the screening assessment)
   * Hemoglobin ≥8 g/dL (criteria must be met without packed red blood cell transfusion ≤1 week before the screening assessment; chronic treatment with erythropoietin 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) and activated partial thromboplastin time ≤1.5 × ULN (except patients who are receiving therapeutic 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. Actual body weight should be used for calculating creatinine clearance. For patients with a body 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 of childbearing potential.
12. Willingness to abide by the contraceptive requirements in Appendix 1 of the protocol.

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. All patients must be previously treated with an immune checkpoint inhibitor either as monotherapy or in combination with chemotherapy. Patients treated with upfront combination chemo-immunotherapy followed by immunotherapy maintenance are considered to have received only 1 prior line of therapy. Chemotherapy given as part of treatment for locally advanced disease in the adjuvant or neoadjuvant setting is not considered a line of prior therapy for recurrent/metastatic disease. If the patient received prior treatment with Cetuximab, paclitaxel, or nab-paclitaxel in combination with radiation in the locally advanced setting and no relapse within 6 months of treatment discontinuation, enrollment is permitted if the treating physician believes that retreatment with Cetuximab or a taxane is a clinically reasonable option. However, patients who received these agents for recurrent or metastatic disease will be excluded.
4. Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, that in the judgment of the investigator could compromise the patient's safety or the study data integrity.
5. Preexisting sensory neuropathy of Grade \>1 severity by NCI CTCAE version 5.0 criteria.
6. Known history of uncontrolled HIV infection defined as CD4+ cells \<350/mm3.
7. Requirement of systemic steroids at daily doses \>10 mg prednisone equivalent systemic exposure daily, including for control of symptoms.
8. Use of any CYP2C8 and CYP3A4 inhibitor (eg, ketoconazole and other imidazole antifungals, 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 dose of study drug until the last PK sample is obtained in the study.
9. Known brain metastasis. Note: Patients whose central nervous system metastases have been treated by surgery or radiotherapy, who are no longer on corticosteroids, and who are neurologically stable are eligible.
10. Current or recent participation in a study of an investigational product in the prior 4 weeks. Note: Patients who have completed the treatment phase of an investigational study and have entered the follow-up phase of the investigational study may participate in FID-007-003 as long as it has been ≥4 weeks before the first dose of study drug.
11. Pregnancy, breastfeeding, or plans to become pregnant during the study or within 24 weeks 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 24 weeks after the last dose of study drug (Appendix 1 of the protocol).