891P - Pembrolizumab and olaparib in recurrent/metastatic, platinum resistant nasopharyngeal cancer: The POINT study

Background

Treatment of platinum-pretreated recurrent/metastatic (RM) Nasopharyngeal Carcinoma (NPC) with pembrolizumab didn’t improve overall survival (OS) vs investigator-choice chemotherapy; its objective response rate (ORR) was 21.4% vs 23.3%. We aimed at assessing the combination of anti PD-1 and PARP inhibitor in this disease setting.

Methods

This is a multicentre, open-label, single-arm phase II study enrolling platinum-resistant RM NPC patients (pts). Eligible pts received pembrolizumab 200 mg every 3-weeks and olaparib 300 mg twice a day every day. Treatment continued until objective disease progression, any prohibitive toxicity or up to 2 years. Primary endpoint was investigators assessed ORR by the 3rd radiological examination (week 27). Secondary endpoints: safety, Progression-Free Survival (PFS), OS, quality of life and translational analysis.

Results

A total of 34 pts (2 screening failure) from 9 Italian centres were enrolled between April 2022 and November 2023. Overall, 25 were males (74%), with a median age of 55 (range 33-75). At baseline, 41% of pts had locoregional disease only, 53% were metastatic and 6% had both; 81% had ECOG PS 0. Circulating EBV DNA tested positive in 74% of pts. The median follow-up on trial was 5.2 months (range 1.9 – 20.6+ months). The median number of administered cycles was 8.7 (range 2-30); 8 patients were still on treatment at data cut-off. The ORR was 13%, with one complete response reported (3%); disease control rate was 38%. Median PFS was 4 months (range 1.7 – 20.6+ months); median OS was not reached. Overall, 84% patients experienced at least one adverse event (AE), while 22% experienced a ≥G3 AE, the most common ones being anaemia (9%) and lymphopenia (6%).

Conclusions

Pembrolizumab plus olaparib failed in enhancing ORR of platinum-refractory RM NPC pts compared to historical data. The combination strategy was well tolerated, with no new safety signals. Further studies aiming at improving the activity and efficacy of immunotherapy in RM NPC are needed.

Clinical trial identification

NCT04825990.

Editorial acknowledgement

Legal entity responsible for the study

GONO Foundation.

Funding

Has not received any funding.

Disclosure

C. Resteghini: Financial Interests, Personal, Invited Speaker: SunPharma. P. Bossi: Financial Interests, Personal, Advisory Board: MSD, Merck, Sanofi, SunPharma, GSK, Molteni, Angelini, Nestlè; Financial Interests, Institutional, Coordinating PI: MSD, GSK, Pfizer, Kyowa Kyrin; Non-Financial Interests, Leadership Role, National research group - Board of Directors: GONO; Non-Financial Interests, Leadership Role, Board of Directors: MASCC. All other authors have declared no conflicts of interest.