Study of Cetuximab Plus/Minus Weekly Paclitaxel After Progression To First-Line Pembrolizumab Plus Platinum-5FU in Subjects With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck.

Exclusion Criteria

• •1. Patients with tumors of the head and neck region, arising from the nasopharynx, nasal cavity, paranasal sinuses, salivary glands, skin, unknown primary site.
• •2. Patients not treated or not progressing to pembrolizumab + platinum / 5-FU as the first line prior to their enrollment in the study. Progression to platinum / 5-FU plus pembrolizumab or other antiPD-(L)1 agents in combination with other immunotherapies including but not limited to other checkpoint regulatory monoclonal/bispecific antibodies such as anti CTLA-4, anti LAG-3 , anti TIGIT or anti TIM-3 may be allowed upon discussion with the sponsor.
• •3. Any previous treatment with paclitaxel and/or cetuximab in the recurrent or metastatic setting.
• •4. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• •Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging (using the identical imaging modality for each assessment, either MRI or CT scan) for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• •5. Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g. tumor bleeding, uncontrolled tumor pain) in the opinion of the treating investigator.
• •6. History of another primary malignancy, except for:
• •1. Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence,
• •2. Adequately treated non-melanoma skin cancer without evidence of disease,
• •3. Adequately treated carcinoma in situ without evidence of disease.
• •7. Any previous surgical treatment of the current cancer (except for a diagnostic biopsy) and no major surgery within 28 days prior to study treatment initiation. Performance of a tracheostomy or placement of a percutaneous gastrostomy tube within the 28 days prior to study treatment initiation will be allowed if the patient is clinically stable with no complications derived from those interventions.
• •8. Focal radiotherapy (RT) with palliative intent that is not completed 2 weeks prior to the first dose of Cetuximab +/- Paclitaxel.
• •9. History of allergic or hypersensitivity reactions to any study drugs or their excipients.
• •10. History of allogeneic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of study treatment initiation or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction.
• •11. Any concurrent chemotherapy, biologic, immunologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
• •12. Current or prior use of immunosuppressive medication within 7 days prior to starting dosing. The following are exceptions to these criteria:
• •1. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection).
• •2. Adrenal replacement steroid \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• •3. Steroids as premedication for hypersensitivity reactions (eg, computed tomography scan premedication).
• •4. \< 10 mg prednisone or equivalent are permitted for the treatment of G1 IRAEs.
• •14. History of primary immune deficiency. History of organ transplant that requires use of immunosuppressive medications. Subjects who are human immunodeficiency (HIV) positive. Participants under definitive treatment for HIV (HAART) with undetectable viral load and \>500 CD4+ T lymphocytes per μL at Screening Visit, are allowed.
• •15. History of stroke or transient ischemic attack within the previous 6 months.
• •16. Any of the following cardiac abnormalities:
• •1. Unstable angina pectoris,
• •2. Congestive heart failure ≥ NYHA Class 2,
• •3. QTc (Fridericia formula) \> 450 for males and \> 470 ms for females,
• •4. Known Left ventricular ejection fraction (LVEF) \< 50,
• •5. Unstable cardiac arrhythmia.
• •17. Pre-existing neuropathy ≥ Grade 2 per NCI CTCAE v5.0.
• •18. With history of interstitial lung disease, noninfectious pneumonitis, severe COPD, or uncontrolled lung diseases, including pulmonary fibrosis. However, specific cases may be allowed upon discussion with the sponsor.
• •19. Has a known history of or is positive for active hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (defined as HCV RNA \[qualitative\] is detected).
• •Note: HBV DNA must be undetectable and HBsAg negative at Screening Visit. Active chronic hepatitis B on antiviral treatment with a negative viral load and preserved liver function is permitted upon consultation with the sponsor.
• •Participants who have had definitive treatment for HCV are permitted if HCV RNA is undetectable at Screening Visit.
• •20. Female patients who are pregnant or breast-feeding.
• •21. Uncontrolled intercurrent illness including, but not limited to, ongoing or active clinically significant infection requiring parenteral antibiotics 2 weeks before treatment start,
• •22. Uncontrolled intercurrent psychiatric illness/social situations that would limit compliance with study requirements.
• •23. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study regimen or interpretation of patient safety or study results.