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 by Kao et al at ESMO Asia Virtual Congress 2020 (Abstract 266O).
According to the presenting authors, 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 the addition of CTLA-4 blockade would suppress T-regulatory function and complement PD-1 blockade in a study of ipilimumab in combination with nivolumab.
Study Methods
The phase II trial 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 an Eastern Cooperative Oncology Group performance status of 0–1, adequate organ function, and to have received no more than one prior line of chemotherapy.
All study participants were treated with nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 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 = 23–73) 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 according to Response Evaluation Criteria in Solid Tumors version 1.1. Toxicity was assessed using Common Terminology Criteria for Adverse Events criteria.
At the ESMO Asia Virtual Congress 2020, findings from an updated efficacy and safety analysis of this single-arm, Simon two-stage study were presented, which incorporated a preplanned expansion for safety and efficacy.
Analysis Findings
At data cutoff in February 2020, patients had received a median of four treatment cycles and six (15%) patients remained on study.
The best overall response 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 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 occurred in 34 (85%) patients, including maculopapular rash in 40% and hypothyroidism in 28%. Four (10%) patients had grade 3/4 serious treatment-related adverse events, including hypocortisolism, pneumonia, myasthenia gravis, and increased lipase.
No relationship was observed between response and either tumor 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 was active based upon the demonstration of durable responses and progression-free survival data as well as safe in patients with nasopharyngeal carcinoma.
The authors suggested that the combination may provide a possible alternative to salvage chemotherapy, and merits further study to incorporate into future clinical trials and treatment paradigms in nasopharyngeal carcinoma.
Disclosure: This study was supported in part by Bristol Myers Squibb and Ono Pharmaceutical. For full disclosures of the study authors, visit oncologypro.esmo.org.
