An open-label, single-arm, multi-institutional phase II trial of avelumab for recurrent, metastatic nasopharyngeal carcinoma.

Abstract

TPS6092 Background: The majority of patients with nasopharyngeal carcinoma (NPC) present with locally advanced disease, with a predilection for early systemic dissemination. For patients who develop recurrent and/or metastatic (R/M) NPC, survival is poor. Following first-line platinum-based regimens, there is no well-defined paradigm for subsequent therapies. Inhibition of PD-L1 with Avelumab is an attractive strategy because Epstein-Barr virus (EBV), the primary causative agent in NPC pathogenesis, universally upregulates PD-L1 expression; proposed mechanisms of upregulation include immune resistance via innate (EBV-induced latent membrane protein-1) and adaptive (Interferon-gamma) mechanisms; increased PD-L1 expression is an independent poor prognostic factor for disease-free survival. Methods: Patients with histologically/cytologically confirmed, EBV-related NPC not amenable to curative intent therapy who received ≥1 prior line of systemic therapy for R/M disease are eligible. Patients must be at least 18 years old, ECOG 0-2, willing to undergo tumor biopsy, have adequate organ and marrow function, and no prior therapy with PD-1/PD-L1 inhibitors. 39 patients will be enrolled across 6 sites. Patients will receive Avelumab 10 mg/kg IV on days 1 and 15 of each 28-day cycle. Treatment will continue until disease progression, unacceptable toxicity, investigator/patient decision. A newly obtained tumor specimen is required at enrollment; optional biopsy at time of progression. EBV plasma DNA titers will be evaluated at baseline, during treatment and at progression, using an EBV BamHI-W DNA PCR. Blood samples at baseline and 12 weeks after treatment initiation will be obtained for correlatives. Primary endpoint is overall response rate (ORR; complete and partial responses) at 6 months per RECIST. A two-stage design will reject H0 (ORR 15%) if the observed ORR is ≥30%, α 0.1, β 0.8, required sample size n = 39. Secondary endpoints include duration of response, progression-free and overall survival. Correlative analyses will evaluate PD-L1 expression, T and B-cell subsets, frequency and clonality. The study has accrued 2 of planned 39 patients. NCT02875613. Clinical trial information: NCT02875613.