Paclitaxel Plus Cetuximab After First-line Checkpoint Inhibitor Failure

Inclusion Criteria:

• The patient has provided written informed consent prior to any study-relatedprocedure.

• The patient is at least 18 years of age

• Histologically proven locally advanced unresectable, recurrent and/or metastaticsquamous cell carcinoma of the oropharynx, hypopharynx, larynx or oral cavity notamenable for salvage surgery

• p16 status has to be determined for oropharyngeal carcinomas

• Documented progressive disease based on investigator assessment according to RECIST 1.1, following receipt of a pembrolizumab based regimen given as first line therapyfor R/M SCCHN

• Measurable disease according to RECIST 1.1.

• The patient has a life expectancy of at least 3 months.

• Has a performance status of ≤ 2 on the ECOG Performance Scale

• Female patient of childbearing potential should have a negative urine or serumpregnancy prior to study . If the urine test is positive or cannot be confirmed asnegative, a serum pregnancy test will be required.

• Female patients of childbearing potential should be willing to use 2 methods ofbirth control or be surgically sterile, or abstain from heterosexual activity forthe course of the study until 120 days after the last dose of study medication.Patients of childbearing potential are those who have not been surgically sterilizedor have not been free from menses for > 1 year.

• Male patients should agree to use an adequate method of contraception starting withthe first dose of study therapy until 120 days after the last dose of study therapy.

• Demonstrate adequate organ function as defined in table 1, all screening labs shouldbe performed within 14 days of treatment initiation.

Exclusion Criteria:

• Prior taxane therapy is not allowed except as part of induction therapy for locallyadvanced disease (completed at least 6 months before study entry)

• Prior cetuximab therapy is not allowed except as part of either induction therapy orin combination with radiotherapy treatment for locally advanced disease (completedat least 6 months before study entry)

• Patients with nasopharyngeal carcinomas or salivary glands cancers

• Is currently participating and receiving study therapy or has participated in astudy of an investigational agent and received study therapy within 4 weeks of thefirst dose of treatment.

• Has a diagnosis of immunodeficiency including a known history of HumanImmunodeficiency Virus (HIV) (HIV 1/2 antibodies).

• Has known active Hepatitis A/B or Hepatitis C

• Has had prior pembrolizumab within 2 weeks prior to study day 1 or who has notrecovered (i.e., recovery to ≤ Grade 1 or baseline grade prior to pembrolizumab)from (immune- related) adverse events other than endocrine side effects.

• Has had prior chemotherapy or radiation therapy within 2 weeks prior to study day 1or who has not recovered (i.e., recovery to ≤ Grade 1 or baseline grade prior topembrolizumab) from adverse events due to a previously administered agent.

• Has had chemotherapy, targeted therapy or investigational drugs after checkpointinhibitor failure for second line therapy .

• Has a known additional malignancy that is progressing or requires active treatment.Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma ofthe skin that has undergone potentially curative therapy or in situ cervical cancer.

• Has an active infection requiring systemic therapy.

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the trial, interfere with thepatient's participation for the full duration of the trial, or is not in the bestinterest of the patient to participate, in the opinion of the treating investigator.

• Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

• Is pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the trial, starting with the pre-screening or screening visituntil 120 days after the last dose of trial treatment.