Phase 2, open-label, multicentre, single-arm study to evaluate the activity of the combination of EGFR inhibitors and c-MET inhibitors in patients with platinum-resistant head and neck squamous cell carcinoma after relapse to immunotherapy.

Prior treatment

• Prior treatment with a hepatocyte growth factor (HGF)/cMet inhibitor such as rilotumumab, crizotinib, MetMAb, or ARQ197
• Uncontrolled central nervous system (CNS) metastases, including leptomeningeal metastases, are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without steroid treatment for at least 2 weeks (radiotherapy or surgery)
• Failure to recover to grade 1 or baseline from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, immunotherapy, and/or experimental therapy, with the exception of: alopecia, grade =< 2 peripheral neuropathy, grade =< 2 cetuximab-related rash or other skin changes, hypomagnesemia (acceptable values detailed below), hypokalemia (acceptable values detailed below), and the acceptable hematologic values summarized above; a washout period of 3 weeks from any prior cytotoxic chemotherapy, targeted therapy, immunotherapy or investigational drug is required
• Previous treatment with cetuximab for RM disease. Use of cetuximab is allowed if given concurrently with radiation

Other illness

• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agen
• Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis
• Peripheral edema >= grade 2 per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

• Adults >= 18 years old
• Histologically confirmed HNSCC from any primary site; nasopharyngeal carcinoma and paranasal sinus, will be included; squamous cell carcinoma of unknown primary, clearly related to the head and neck, will be included
• Recurrent/metastatic disease, fulfilling at least one of the criteria defined below: a) Incurable disease as assessed by surgical or radiation oncology b) Metastatic (M1) disease c) Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity; patients who decline radical surgery are eligible
• For patients with oropharyngeal primary site or unknown primary site only: tumoral human papillomavirus (HPV) status must be negative, as established; 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 deoxyribonucleic acid (DNA) For patients with nasopharyngeal cancer only or unknown primary site only: tumoral Epstein- Barr Virus (EBV) status must be negative.