Fang W, et al. - In patients with recurrent or metastatic nasopharyngeal carcinoma, researchers presented safety and preliminary antitumor activity of camrelizumab alone as second-line therapy and combined with gemcitabine and cisplatin as first-line therapy. For patients with recurrent or metastatic nasopharyngeal carcinoma, camrelizumab is a well-tolerated, possible treatment choice. In treatment-naive patients, the combination of camrelizumab plus gemcitabine and cisplatin has a manageable toxicity profile and promising preliminary antitumor activity for this disease.

Methods

• Researchers report the outcomes from two single-arm, phase 1 trials.
• Both trials involved subjects aged 18–70 years with histologically or cytologically confirmed nasopharyngeal carcinoma and confirmed metastatic disease or locoreginal recurrence, and an Eastern Cooperative Oncology Group performance status of 0 or 1.
• Subjects who received at least one previous line of treatment were selected at five academic hospitals in China into the dose-escalation and expansion trial to receive camrelizumab monotherapy intravenously at escalating doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg, and a bridging dose of 200 mg per dose once every 2 weeks (monotherapy trial).
• Treatment-naive subjects were enlisted from a single center in China to receive six cycles of camrelizumab 200 mg (day 1), gemcitabine 1 g/m ² (days 1 and 8), and cisplatin 80 mg/m ² (day 1) every 3 weeks followed by camrelizumab 200 mg maintenance once every 3 weeks (combination trial).
• The safety and tolerability of the study treatment was the primary endpoint of both trials.
• Both trials are ongoing but are no longer enrolling subjects.

Results

• Between March 31, 2016, and September 20, 2017, 121 subjects were assessed for eligibility, of whom 93 patients were enrolled across the dose-escalation and expansion cohorts and received at least one dose of camrelizumab (safety population) in the camrelizumab monotherapy trial.
• It was observed that 15 (16%) of 93 subjects had treatment-related adverse events of grade 3 or 4, the most common of which were elevated conjugated bilirubin concentration (three [3%] of 93 patients), stomatitis, anemia, and increased concentrations of aspartate aminotransferase, alanine aminotransferase, and total bilirubin, each of which occurred in two (2%) patients.
• Treatment-related serious adverse events were found in 8 (9%) patients.
• During the dose-escalation phase, no dose-limiting toxic effects were seen.
• Researchers found that 31 (34%; 95% CI 24–44) of 91 evaluable patients on camrelizumab monotherapy had an overall response with a median follow-up of 9.9 months (IQR 8.1–11.7).
• Between April 18, 2017, and August 15, 2017, 24 patients were assessed for eligibility, of whom 23 patients were enlisted and treated (safety population) in the camrelizumab combination trial.
• They discovered that 20 (87%) of 23 subjects had grade 3 or 4 treatment-related adverse events: neutropenia (13 [57%] of 23 patients), anemia (11 [48%] patients), leucopenia (11 [48%] patients), thrombocytopenia (seven [30%] patients), edema (two [9%] patients), hyponatremia (two [9%] patients), hypochloremia (one [4%] patients), and rash (one [4%] patient).
• Treatment-related serious adverse events were seen in 2 patients.
• In these trials, no treatment-related deaths occurred.
• The present data indicated that 20 (91% [95% CI 72–97]) of 22 evaluable patients had an overall response with a median follow-up time of 10.2 months (IQR 9.7–10.8).