A Phase I/II Open-Label Study of Nivolumab in Previously Treated Advanced or Recurrent Nasopharyngeal Carcinoma and Other Solid Tumors

Yuxiang Ma, Wenfeng Fang, Yang Zhang, Yunpeng Yang, Shaodong Hong, Yuanyuan Zhao, Amol Tendolkar, Lu Chen, Dong Xu, Jennifer Sheng, Hongyun Zhao, Li Zhang, Yuxiang Ma, Wenfeng Fang, Yang Zhang, Yunpeng Yang, Shaodong Hong, Yuanyuan Zhao, Amol Tendolkar, Lu Chen, Dong Xu, Jennifer Sheng, Hongyun Zhao, Li Zhang

Abstract

Lessons learned: Nivolumab treatment at doses of 3 mg/kg once every 2 weeks (Q2W), 240 mg Q2W, and 360 mg once every 3 weeks was well tolerated in the Chinese population, with no new safety signals identified.Comparison of intensive pharmacokinetic profiles of nivolumab at 3 mg/kg Q2W in Chinese versus global populations revealed no ethnic differences of nivolumab treatment.Nivolumab shows promising preliminary antitumor activity in nasopharyngeal carcinoma.

Background: This phase I/II study investigated the safety and pharmacokinetics (PK) of nivolumab (anti-programmed cell death-1 monoclonal antibody) in Chinese patients with nasopharyngeal carcinoma (NPC) and other solid tumors.

Methods: A dose evaluation phase (3 mg/kg once every 2 weeks [Q2W]) was followed by a cohort expansion phase (3 mg/kg Q2W or flat doses of 240 mg Q2W or 360 mg once every 3 weeks).

Results: In the dose evaluation phase, 8/8 patients completed one cycle with no dose-limiting toxicities. At data cutoff, 46/51 patients were evaluable for safety (all cohorts). Treatment-related adverse events (TRAEs) occurred in 35 (76%) patients and were primarily grade 1-2; one patient (3 mg/kg Q2W) discontinued because of study drug toxicity. Intensive PK profiles at 3 mg/kg, 240 mg, and 360 mg were well characterized at single and multiple doses of nivolumab. An objective response was determined in six (6/46) patients, four (4/32) of whom had NPC tumors.

Conclusion: Nivolumab monotherapy at 3 mg/kg and flat doses of 240 mg and 360 mg were well tolerated in this Chinese patient population, with PK profiles at 3 mg/kg being similar to those of global patients. Preliminary efficacy results showed promising antitumor activity of nivolumab in advanced NPC.

Trial registration: ClinicalTrials.gov NCT02593786.

© AlphaMed Press; the data published online to support this summary are the property of the authors.

Figures

Figure 1.
Figure 1.
Patient disposition flow chart. *Death due to septic shock considered unrelated to the study drug. †Treatment status unconfirmed at the time of database lock. Abbreviation: AE, adverse event.
Figure 2.
Figure 2.
Pharmacokinetics of nivolumab. (A): Mean serum concentration‐time profiles of nivolumab after single‐dose administration. (B): Mean serum concentration‐time profiles of nivolumab at steady state. (C): Geometric mean trough concentration profiles of nivolumab. For all figures: A, 3 mg/kg; B, 240 mg; C, 360 mg. Logarithmic scale. Bars indicate SD.
Figure 3.
Figure 3.
Waterfall plot of best reduction from baseline in target lesions for patients with nasopharyngeal carcinoma. Abbreviation: PR, partial response.
Figure 4.
Figure 4.
Tumor swimmer plot for the subpopulation of patients with nasopharyngeal carcinoma. Abbreviations: PR, partial response; SD, stable disease.

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