A Phase II Clinical Study of Treprilimab in the Treatment of Recurrent Nasopharyngeal Carcinoma After Re-irradiation

To establish the antitumor activity and safety of the anti-programmed death 1 receptor monoclonal antibody, Treprilimab, in patients with local recurrent/residual nasopharyngeal carcinoma after re-irradiation.Patients with local recurrent/residual NPC after re-irradiation were treated with Treprilimab until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity.The sample size of this study was estimated on the assumption that response rates (RRs) to Treprilimab should be around 25%,based on a report that was available at the time this study was planned.Furthermore, the RR to noncytotoxic, experimental agents such as pazopanib and cetuximab in similarly pretreated patient cohorts was approximately 5% to 10%. This study's design was based on the modified Simon two-stage optimal design (α=0.05，β=0.2,n1=2/22,n2=7/40). If two responses were observed during the first stage, enrollment was continued until a total of 40 patients was reached.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

Inclusion Criteria:

* ages from 18 years to 65 years.
* Histologically confirmed local recurrent/residual Nasopharyngeal carcinoma with previous re-irradiation.
* measurable disease at baseline on the basis of RECIST v1.1.
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* adequate organ function.
* anticipate survival≥3 months.

Exclusion Criteria:

* a diagnosis of immuno deficiency or systemic corticosteroid therapy within 14 days of study start.
* prior anticancer monoclonal antibody therapy within 4 weeks of study start.
* any anticancer therapy within 4 weeks preceding the study start.
* therapy with any other immune checkpoint inhibitor.
* active autoimmune disease, interstitial lung disease, known additional malignancy that was progressing or that required active treatment.
* not received platinum based chemotherapy previously.
* confirmed systemic metastasis
* HBV positive and Child-Pugh B or C cirrhosis
* HCV positive and Child-Pugh B or C cirrhosis

• BACKGROUNDMa BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27. PMID 29584545
• BACKGROUNDHsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24. PMID 28837405
• BACKGROUNDChan AT, Hsu MM, Goh BC, Hui EP, Liu TW, Millward MJ, Hong RL, Whang-Peng J, Ma BB, To KF, Mueser M, Amellal N, Lin X, Chang AY. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005 May 20;23(15):3568-76. doi: 10.1200/JCO.2005.02.147. Epub 2005 Apr 4. PMID 15809453
• BACKGROUNDZhou Y, Miao J, Wu H, Tang H, Kuang J, Zhou X, Peng Y, Hu D, Shi D, Deng W, Cao X, Zhao C, Xie C. PD-1 and PD-L1 expression in 132 recurrent nasopharyngeal carcinoma: the correlation with anemia and outcomes. Oncotarget. 2017 Apr 19;8(31):51210-51223. doi: 10.18632/oncotarget.17214. eCollection 2017 Aug 1. PMID 28881642