Safety of tabelecleucel with pembrolizumab in recurrent/metastatic Epstein–Barr virus-associated nasopharyngeal carcinoma.

6096 Background: Despite standard treatment with radiation and/or chemotherapy, approximately one in four patients (pts) with nasopharyngeal carcinoma (NPC) will develop recurrent/metastatic (RM) disease that is associated with poor prognosis. Programmed cell death ligand 1 (PD-L1) expression is upregulated in NPC due to Epstein–Barr virus (EBV) activation. Tabelecleucel (tab-cel), an off-the-shelf, allogeneic, EBV-specific T-cell immunotherapy, has shown promising antitumor activity in pts with RM EBV + NPC (Prockop, JCO 2016). The anti-PD-1 antibody pembrolizumab (pembro) is also active in NPC. To characterize the safety profile and preliminary efficacy of tab-cel combined with pembro in RM EBV + NPC, we initiated a phase 1b/2 study (NCT03769467). Here we report safety outcomes in 12 subjects treated in the phase 1b portion of the study. Methods: The multicenter, open-label, single-arm phase 1b portion of the study was designed to evaluate the safety of tab-cel in combination with pembro in pts with incurable RM EBV + NPC previously treated with platinum-containing therapy. Pts were either checkpoint-inhibitor naïve (n=6) or experienced to anti-PD-1/PD-L1 therapy (n=6). Tab-cel was administered intravenously (IV) on days 1, 8, and 15 of a 21-day cycle. Initial tab-cel dose was 2x10 6 cells/kg. Pembro was administered at 200 mg IV Q3W. Primary endpoints of phase 1b focused on assessing safety. Results: As of the final data cutoff, 12 subjects were treated as part of the phase 1b portion of the study. Subjects were 75% Asian and 50% male, with a median age (min, max) of 51 (20, 72) years and a median time from initial diagnosis to first dose of tab-cel (min, max) of 47.7 (8.0, 221.8) months. All subjects had received prior platinum-based chemotherapy/chemoradiation. No dose-limiting toxicities or fatal treatment-emergent adverse events (TEAEs) were identified. All 12 subjects reported ≥1 TEAE; the most common TEAEs reported by ≥4 subjects were disease progression (8 subjects, 66.7%), myalgia (5 subjects, 41.7%), pyrexia, arthralgia, and hyponatremia (4 subjects, 33.3%, each). No ≥ grade 3 TEAEs were considered related to tab-cel or pembro. No TEAEs considered related to tab-cel or pembro led to study discontinuation. No clinically significant abnormal trends were identified in laboratory parameters or vital signs. Although the phase 1b portion of the study was not designed to assess efficacy, the best response seen was stable disease in 6 of 12 pts (50%). Conclusions: Phase 1b data demonstrated combination therapy of tab-cel and pembro to be well tolerated and identified a recommended phase 2 dose in subjects with platinum-pretreated RM EBV + NPC. The study was discontinued after the phase Ib portion due to an evolving immunotherapy treatment landscape for this disease, which would need to be considered for further clinical development. Clinical trial information: NCT03769467 .