894P - AXEL: AXitinib-avELumab combination in recurrent or metastatic (RM) nasopharyngeal cancer (NPC)

Background

Several combinations of Vascular Endothelial Growth Factor inhibitor (VEGFi) and Immune Checkpoint Inhibitor (ICI) had reported synergistic antitumor activities in solid tumors. We investigated the efficacy and safety of the VEGFi + ICI combination, axitinib and avelumab, in RM NPC.

Methods

This single arm, Simon’s minimax 2-stage, phase II study enrolled patients with RM NPC refractory to at least one line of platinum-based chemotherapy and treatment naive to ICI. Patients received axitinib 5 mg bd po daily and avelumab 10 mg/kg IV on Day 1 and 15 of every 4-week cycles until progression or intolerance. The primary endpoint was objective response rate (ORR) by RECIST v1.1. Key secondary endpoints included safety, disease control rate (DCR), progression free survival (PFS), overall survival (OS), and correlation of plasma EBV DNA response.

Results

Between 10 June 2021 and 15 Nov 2022, 13 patients were enrolled in stage I and were included in the efficacy and safety analysis. Patients received a median of 3 lines of prior chemotherapy (range 1-6) before study enrolment. All except one patient received prior radiotherapy. Patients completed a median of 6 cycles (range 3-18) of study treatment. The ORR was 7.7% with 1 confirmed partial response (PR), 7 stable diseases (including 2 unconfirmed PR) and 5 progressive diseases (including 2 mixed responses). As the ORR did not meet the prespecified criteria (<20%), the study was closed at stage I. DCR was 61.5% and 38.4% at 3 and 6 months. After a median follow up of 26.7 months (data cutoff 29 Feb 2024), 12 patients had progressed, and 8 patients died. The median PFS and OS was 5.4 and 15.0 months respectively. The most common treatment related adverse events (TRAE) were hand foot syndrome (n=9), hypertension (n=8), diarrhea (n=7), hypothyroidism (n=7), and fatigue (n=5). There was no grade 4/5 TRAE. Plasma EBV DNA responses at 4 weeks correlated with PFS (median 7.4 vs 3.6 months, p= 0.028) and OS (not reached vs 8.9 months), but not with RECIST responses.

Conclusions

In heavily pre-treated RM NPC, axitinib-avelumab combination achieved favorable DCR and median PFS, despite the low ORR by RECIST criteria. Stable disease and mixed response patterns were more common. Early EBV DNA response was strong predictor of PFS and OS.

Clinical trial identification

NCT04562441.

Editorial acknowledgement

Legal entity responsible for the study

Comprehensive Cancer Trial Unit, The Chinese University of Hong Kong.

Funding

Pfizer, Charlie Lee precision immunology, Kingboard precision oncology, and Research Grant Council (RGC 2141320).

Disclosure

E.P. Hui: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: MSD, Pfizer. B.B.Y. Ma: Financial Interests, Personal, Invited Speaker, Advisory Board/Consultancy: Novartis, BMS, MSD; Financial Interests, Personal, Advisory Board, Consultancy: Y-biologics, Boehringer Ingelheim, Merck Serono; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board, Ad board and consultancy: Viracta Therapeutics; Financial Interests, Personal, Other, Consultancy: Alentis; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Merck Serono; Financial Interests, Institutional, Research Grant, Research Grant Preclinical: Novartis; Non-Financial Interests, Principal Investigator, NRG oncology study PI: NRG oncology. C.M. Chan: Financial Interests, Institutional, Full or part-time Employment, Scientific Officer: The Chinese University of Hong Kong. W.K.J. Lam: Financial Interests, Personal, Stocks/Shares: Grail/ Illumina; Financial Interests, Institutional, Royalties: Grail; Non-Financial Interests, Leadership Role, I am a Director of the DRA: DRA. A.T. Chan: Financial Interests, Personal, Advisory Board: MSD, Tessa Therapeutics Ltd; Financial Interests, Personal, Other, Consultancy: MSD; Financial Interests, Personal, Other, Biomarker testing for MK-3475 KN122 program: MSD; Financial Interests, Personal, Writing Engagement: Springer; Financial Interests, Personal, Other, Travel and accommodation expenses to attend conference: Roche; Financial Interests, Institutional, Research Grant, Neoadjuvant Pembrolizumab-Gemcitabine-Cisplatin Followed by Concurrent Pembrolizumab-Chemoradiation and Maintenance Pembrolizumab for Stage IVA Nasopharyngeal Cancer: Merck Sharp & Dohme (Asia) Ltd; Financial Interests, Institutional, Research Grant, Biomarker study for NEO-SPACE MISP-56746: MSD International GmbH; Financial Interests, Institutional, Research Grant, AXEL - Axitinib-Avelumab Combination in Recurrent or Metastatic Nasopharyngeal Cancer - A Multicenter Phase II Trial: Pfizer Corporation Hong Kong Limited; Financial Interests, Institutional, Research Grant, Clinical Development of a Urine Test for Screening Urinary Tract Cancers: Angene Biotechnology Limited; Financial Interests, Institutional, Research Grant, NRG Oncology #HN007 An Open-label, Phase II Study of Platinum-Gemcitabine With or Without Nivolumab in the First Line of Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma: NRG Oncology Foundation, Inc.; Non-Financial Interests, Advisory Role: Immunomic Therapeutics, Inc, Angene Biotechnology Limited, Owlstone Medical Limited. All other authors have declared no conflicts of interest.