Dual CTLA-4/PD-1 blockade with ipilimumab plus nivolumab provided durable responses in patients with recurrent or metastatic nasopharyngeal carcinoma, according to updated efficacy and safety findings from a phase II study presented at the ESMO Asia Virtual Congress 2020, held from 20 to 22 November 2020.
According to Dr. Hsiang-Fong Kao of the Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center in Taipei, Taiwan, nasopharyngeal carcinoma shows T-regulatory cell infiltration and high PD-L1 expression, yet monotherapy targeting PD-1/PD-L1 has shown limited activity. This observation led to investigation of whether CTLA-4 blockade would suppress T-regulatory function and complement PD-1 blockade in a phase II study of ipilimumab in combination with nivolumab (NCT03097939).
The study led by Dr Darren Wan-Teck Lim from the National Cancer Centre Singapore, enrolled 40 patients from July 2017 to September 2019 from Singapore and Taiwan with recurrent/metastatic nasopharyngeal carcinoma and measurable plasma Epstein Barr virus DNA. The patients were further required to have ECOG performance status 0-1, adequate organ function, and to have received no more than one prior line of chemotherapy.
At the ESMO Asia Virtual Congress 2020, Dr. Kao presented findings from an updated efficacy and safety analysis of this single arm phase II, Simon 2-stage study, which incorporated a preplanned expansion for safety and efficacy.
All study participants were treated with nivolumab at 3 mg/kg every two weeks plus ipilimumab at 1 mg/kg every six weeks. All patients receiving at least one dose of the combination were included in the safety and efficacy analysis. The majority (90.0%) of patients were Chinese with a median age of 53 (range, 23 to 73) years, and 82.5% of patients were male. Prior chemotherapy had been administered to 39 (97.5%) patients.
The primary efficacy endpoint was best overall response (BOR) by RECIST v1.1. Toxicity was assessed using CTCAE criteria.
The ipilimumab/nivolumab combination was safe in patients with nasopharyngeal carcinoma
At data cut-off in February 2020 patients had received a median of 4 treatment cycles and 6 (15%) patients remained on study.
The BOR was partial response, which was achieved by 14 (35%) patients (95% confidence interval [CI] 20.6-51.7%). Responding patients showed a median duration of response of 5.9 months (95% CI 3.95-8.97).
With median follow up of 17.3 months, median progression-free survival (PFS) was 5.3 months (95% CI 3.0-6.4 months), and median overall survival was 17.6 months (95% CI 13.1-30.0).
Treatment-related adverse events (TRAEs) occurred in 34 (85%) patients that included maculopapular rash in 40% and hypothyroidism in 28% of patients. Four (10%) patients had grade 3/4 serious TRAEs including hypocortisolism, pneumonia, myasthenia gravis, and increased lipase.
No relationship was observed between response and either tumour mutation burden or PD-1 expression.
The authors stated that this was the first phase II study of this combination in nasopharyngeal carcinoma. They further concluded that combination treatment with nivolumab and ipilimumab wass active based upon the demonstration of durable responses and PFS data as well as safe in patients with nasopharyngeal carcinoma.
The authors suggest that the combination may provided a possible alternative to salvage chemotherapy and merits further study to incorporate into future clinical trials and treatment paradigms in nasopharyngeal carcinoma.
This study was supported in part by Bristol-Myers Squibb and ONO pharmaceuticals.
266O – Kao H-F, Ang M-K, Ng QS, et al. Combination Ipilimumab and Nivolumab in Recurrent/Metastatic Nasopharyngeal Carcinoma (R/M NPC) – Updated Efficacy and Safety Analysis of NCT03097939. ESMO Asia Virtual Congress 2020 (20-22 November).