Ficlatuzumab w/wo Cetuximab in Patients w/Cetuximab-Resistant, Recurrent or Metastatic Head/Neck Squamous Cell Carcinoma

Inclusion Criteria

• Patients must have histologically confirmed HNSCC from any primary site, except nasopharyngeal if World Health Organization (WHO) Type III (non-keratinizing and Epstein-Barr virus (EBV)-positive)).

Eligible histologies include:

• Basaloid, poorly differentiated, and undifferentiated carcinoma histologies.
• Nasopharyngeal carcinoma, WHO Type I and II (keratinizing, non-EBV positive).
• Paranasal sinus, lip and external auditory canal sites.
• Squamous cell carcinoma of unknown primary, clearly related to the head and neck.

Note: Documentation of primary site diagnosis must be submitted with the registration request.

• Patients must have recurrent and/or metastatic disease, fulfilling at least one of the criteria defined below:
• Incurable disease as assessed by surgical or radiation oncology;
• Metastatic (M1) disease;
• Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity. Note: Patients who decline radical surgery are eligible.
• For patients with oropharyngeal primary site or unknown primary site only: Patients must have known tumoral HPV status (p16). (Acceptable standards include p16 immunohistochemistry (where a tumor is classified as p16-positive when showing diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells) and/or assessment of HPV DNA.) Note: For these subjects, documentation of p16 status must be submitted with the registration packet.
• Patients must be cetuximab-resistant by fulfilling at least one of the two criteria defined below:
• Disease persistence or recurrence within 6 months of completing definitive radiotherapy with concurrent cetuximab for locally advanced disease. Induction chemotherapy, if given, may or may not have included cetuximab.
• Disease progression during, or within 6 months, of cetuximab treatment in the recurrent and/or metastatic setting.

Note: Prior cetuximab exposure may have occurred in any line of therapy (first line, second line, etc.) and is not required to be the most recent therapy received.

• Patients must be platinum-resistant or platinum-ineligible by fulfilling at least one of the three criteria defined below:
• Disease persistence or recurrence within 6 months of completing definitive radiotherapy for locally advanced disease, where platinum chemotherapy was administered as a component of induction and/or concurrent systemic treatment.
• Disease progression during, or within 6 months, of treatment with platinum chemotherapy (e.g., carboplatin or cisplatin) in the recurrent and/or metastatic setting.
• The patient is not an acceptable candidate for platinum chemotherapy due to medical comorbidities, in the judgment of the local investigator.

Note: Prior platinum exposure may have occurred in any line of therapy (first line, second line, etc.) and is not required to be the most recent therapy received.

• Patients must have prior exposure to an anti-PD1 (programmed cell death protein 1) or anti-PDL1 (programmed cell death ligand 1) monoclonal antibody (mAb), if eligible for immunotherapy in the judgment of the local investigator.

Note: Prior exposure to investigational immunotherapies, including anti-CTLA4 (cytotoxic T-lymphocyte-associated antigen 4), anti-OX40, anti-CD40 (cluster of differentiation 40), anti-CD27, anti-TNFR (tumor necrosis factor receptor) antibodies or other investigational immunotherapies, is acceptable.

• Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 at time of informed consent (see Appendix B).
• Patients must be age ≥ 18 years.
• Patients must consent to a research biopsy of tumor tissue at baseline, for conduct of correlative studies. In cases where a fresh biopsy is not feasible (i.e., if an accessible tumor site cannot be biopsied with acceptable clinical risk), archival tissue may be submitted instead, after discussion with and approval by the Sponsor-Investigator.
• Pat