study of medi4736 monotherapy and in combination with tremelimumab versus standard of care therapy in patients with head and neck cancer

Conditions: Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck SCCHN

Summary: this is a randomized, open-label, multi-center, global, phase iii study to determine the efficacy and safety of medi4736 + tremelimumab combination therapy and medi4736 monotherapy versus soc therapy in the target patient population.

this is a randomized, open-label, multi-center, global, phase iii study to determine the efficacy and safety of medi4736 + tremelimumab combination therapy and medi4736 monotherapy versus soc therapy in the target patient population. the main objectives of the study are to: * assess the efficacy of medi4736 + tremelimumab combination therapy versus soc in patients with squamous cell carcinoma of the head and neck (scchn), in terms of overall survival (os), regardless of pdl-1 status * assess the efficacy of medi4736 monotherapy versus soc in patients with scchn, in terms of os, regardless of pdl-1 status patients will undergo a screening assessment on their tumor tissue sample to determine pd-l1 expression per a pre-specified cut-off level. patients with ≥25% of tumor cells with membrane staining will be considered pd-l1 positive while those with 0% to 24% of tumor cells with membrane staining will be considered pd-l1 negative. based on the underlying pd-l1 status, patients will be randomized in a 1:1:1 ratio to receive treatment with medi4736 monotherapy, medi4736 + tremelimumab combination therapy, or soc therapy. patients who discontinue treatment in 1 treatment group may not switch to treatment in a different group. stratification factors include pd-l1 status, human papillomavirus status, (in patients with oropharyngeal cancer only), and smoking status. tumor assessments will be performed every 8 weeks until objective tumor response by response evaluation criteria in solid tumors version 1.1 (recist 1.1).

Eligibility criteria:
inclusion criteria: - age ≥18 years; - written informed consent obtained from the patient/legal representative; - histologically or cytologically confirmed recurrent or metastatic scchn; - tumor progression or recurrence during or after only one palliative systemic treatment regimen for recurrent or metastatic disease that must have contained a platinum agent or progression within 6 months of the last dose of platinum given as part of multimodality therapy with curative intent; - confirmed pd-l1-positive or -negative scchn by the ventana pd-l1 sp263 ihc assay; - who/eastern cooperative oncology group (ecog) performance status of 0 or 1; at least 1 measurable lesion, - not previously irradiated; - no prior exposure to immune-mediated therapy; - adequate organ and marrow function; evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. exclusion criteria: - histologically or cytologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck; - received more than 1 palliative systemic regimen for recurrent or metastatic disease; -any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment; - receipt of any investigational anticancer therapy within 28 days or 5 half-lives; - receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mabs, etc) within 21 days prior to the first dose of study treatment; - major surgical procedure within 28 days prior to the first dose of investigational product; - any unresolved toxicity nci ctcae grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion; - current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned investigational product; - history of allogeneic organ transplantation; - active or prior documented autoimmune or inflammatory disorders; - uncontrolled intercurrent illness; - patients with a history of brain metastases, spinal cord compression, or leptomeningeal carcinomatosis; - mean qt interval corrected for heart rate (qtc) ≥470 ms calculated from 3 electrocardiograms (ecgs) using fridericia's correction; - history of active primary immunodeficiency; - active tuberculosis; - active infection including hepatitis b, hepatitis c or human immunodeficiency virus (hiv); - receipt of live, attenuated vaccine within 30 days prior to the first dose of investigational product; - pregnant or breast-feeding female patients; - known allergy or hypersensitivity to investigational product

Keywords: head and neck cancer; medi4736; tremelimumab