Phase II study of ficerafusp alfa in combination with nivolumab in patients with platinum-refractory head and neck squamous cell carcinoma who progressed within 6 months of multimodality therapy for locally advanced disease.

Prior treatment

• Active central nervous system (CNS) metastases or carcinomatous meningitis. Known active central nervous system metastases, history of spinal cord compression from tumor involvement, a history of carcinomatous meningitis, or leptomeningeal disease are excluded. Patients with a history of treated central nervous system metastases (by surgery or radiation therapy) may be eligible if central nervous system metastases have been stable for at least 4 weeks, i.e., without evidence of progression by repeat imaging and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Subjects having received prior systemic treatment for metastatic or recurrent disease
• Subjects having received prior treatment with anti-TGF-β therapy.
• Subjects having received prior therapy with anti-PD1, anti-PD-L1 (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Patient who participated in another clinical study or received treatment with another investigational drug must wait at least 5 half-lives of the treatment received or 4 weeks (whichever is shorter) following prior therapy or at least 4 weeks if half live of the agent received is not known before enrollment.
• Known to be diagnosed and/or treated for any other additional malignancy within 2 years prior to registration/randomization with the exception of the following: curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, and curatively resected in situ cervical cancer, and curatively resected in situ breast cancer, and low-risk early stage prostate cancer defined as follows: Stage T1 up to T2a with a Gleason score ≤6 and prostatic specific antigen <10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to registration/randomization. Other exceptions may be considered with the Sponsor’s consultation. The time requirement for no malignancy for 2 years does not apply to the cancer for which a patient is enrolled in the study
• Any of the following <6 months before starting study treatment: ST-elevation myocardial infarction, severe/unstable angina, uncontrolled cardiac ventricular arrythmia, coronary/peripheral artery bypass graft or stent, cerebrovascular accident/stroke less than 6 months prior to enrollment or NYHA Class III/IV congestive heart failure. Subjects with deep vein thrombosis who are hemodynamically stable can enroll if they are on a stable dose of anticoagulants for at least 3 months
• Serious systemic infection (bacterial, viral, or fungal) within 4 weeks before first dose of study treatment, or active systemic infection requiring either hospitalization or parenteral anti-infective therapy within 2 weeks before first dose of study treatment.

Other illness

• History of (non-infectious) pneumonitis/ interstitial lung disease or has current pneumonitis/ Interstitial lung disease.
• History of uncontrolled seizures, CNS disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance.

Lab values

• Subjects having received prior treatment with anti-EGFR antibody.

Other

• Primary tumor of nasopharyngeal, paranasal sinuses, nasal cavity or salivary gland, thyroid or parathyroid gland pathologies, skin, squamous cell carcinoma of unknown primary or non-squamous histologies (e.g., mucosal melanoma).

• Patient is >18 years, ≤75 years of age on the day the ICF is signed.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Histologically or cytologically confirmed squamous cell carcinoma of head and neck (HNSCC). Eligible primary tumor locations are oral cavity, larynx hypopharynx, or oropharynx (OPSCC).
• Local, regional or metastatic progression within 6 months after the last dose of platinum in a multimodal strategy for locally advanced stage, not amenable to salvage surgery in case of local or regional progression. Specification regarding inclusion criterion no. 05 : The pProgression is not assessed as per RECIST. and Any of the following that will be considered as a progression any of the following items : o A positive biopsy 3 months after the end of radiotherapy given with curative intent o Appearance of any new lesion (exe.g.: metastases or lymph nodes) o Any increase in tumor size o Any persisting tumor (confirmed with a biopsy) not amenable to salvage surgery
• For OPSCC patients, a pathological report determination of human papillomavirus (HPV) status by p16 expression must be p16 negative
• Measurable tumor lesion(s) assessed by H&N-computed tomography scan (CT-scan) or magnetic resonance imaging (MRI), based on RECIST v 1.1 (see Appendix 3). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated.