Point

Nasopharyngeal carcinoma (NPC) is an uncommon cancer in Europe where the incidence is well below 1/100.000 per year, in contrast with Southeast Asia and Southwest China where the incidence is 20- 30/100.000 per year. Recurrence rate after curative treatment for locally advanced NPC is reported varying from 15% to 30% of cases, while approximately 5-11% of patients present with de novo metastatic disease. Once disease is not amenable to curative treatment (either radiotherapy and/or surgery), patients is eligible for systemic treatment. The standard of care as first line treatment is platinum based combined with gemcitabine. However, once disease becomes platinum resistant, no standard second line treatment exists. With second line chemotherapy based treatment progression free survival and overall survival are assessed as 5 and 12 months respectively. Thus, effective second line treatment in platinum resistant NPC are urgently needed. Immunotherapy with Immune Checkpoint Inhibitors are promising in NPC especially because of the causal role of EBV infection and the possibility to elicit a response against its antigens. Nivolumab, pembrolizumab, and camrelizumab have been shown to be safe and active as monotherapy for recurrent and/or metastatic NPC, with ORRs of 20%, 25%, and 34%, respectively. Moreover, preclinical data, showed how the PARP repair may contribute to platinum resistance in NPC cells to escape apoptosis. In NPC PARP1 is overexpressed in comparison with normal nasopharyngeal cells. Finally, preclinical and clinical data showed the synergistic effect of Immune Checkpoint inhibitor combined with PARP inhibitor. The POINT trial is a phase 2, single arm, open label trial in which platinum resistant recurrent and or metastatic NPC will receive pembrolizumab 200 mg flat dose q3w + olaparib 300 orally twice daily.

Main selection criteria are the following:
– Histological diagnosis of nasopharyngeal carcinoma
– Recurrent and/or metastatic disease not amenable to curative treatment
– Disease progressing within 6 months since previous platinum-based systemic treatment (as concomitant to RT or as first line treatment for RM NPC)
– PS ECOG = 0-1
– Adequate bone marrow and organ function

The primary objective of the trial is to evaluate the activity of study treatment in terms of Objective Response rate. Secondary objectives are the safety of study treatment according to CTCAE v5.0; the progression free survival, and change in quality of life assessed with EORTC QLQ HN-43 questionnaire. The exploratory objectives are the evaluation of prognostic/predictive biomarkers through gene expression analysis, PDL1 expression, tissue immune infiltrate, genomic alteration in p53 and BRCA 1/2, tumor mutational burden (TMB), and serum level of inflammatory cytokines