Abstract CT203: A phase II trial of ipilimumab in combination with nivolumab in EBV-associated advanced nasopharyngeal carcinoma (NCT03097939)

Background: Single agent PD-1/PD-L1 studies in previously treated EBV-associated nasopharyngeal carcinoma (NPC) demonstrate clinical outcomes inferior to salvage combination chemotherapy. Dual blockade of PD-1/CTLA4 is a viable treatment strategy in other solid tumors. We hypothesized that this strategy would also be feasible and efficacious in NPC. Materials and Methods: A single arm phase 2 study using a Simon 2-stage design was used. Nivolumab was dosed at 3 mg/kg q2 weeks, and Ipilimumab was dosed at 1 mg/kg q6 weeks. Eligible pts had EBER-ISH positive NPC, measurable plasma EBV DNA, no more than 1 prior line of chemotherapy, ECOG 0-1, and adequate organ function. All pts who met the eligibility criteria and received at least one dose of the combination were included in the safety and efficacy analysis. The primary efficacy endpoint was best overall response (BOR) by RECIST 1.1. Toxicity was assessed using CTCAE criteria. Pretreatment EBV DNA load was used to discriminate EBVhi from EBVlo at a threshold of 30,000 copies/ml, and sub-group analyses were carried out for BOR, time to progression, progression-free survival and overall survival based on this cutoff. Paired tumor and blood sampling were done at baseline and on-treatment and results are presented separately. Results: A total of 28 patients were enrolled and 26 were evaluable. Two patients were excluded from analysis for eligibility reason and consent withdrawal. Median age of pts was 56 years (range 23-73). Most patients (85%) were of Chinese ethnicity and 19 patients (73%) were male. The median number of cycles received was 4. Three patients remain on treatment. Twenty-one patients (81%) experienced any grade treatment-related adverse events (trAE). Common trAEs were maculopapular rash (n=8; 31%) and hypothyroidism (n=8; 31%). Three pts (11%) required treatment discontinuation due to grade 3/4 AE, including pneumonitis and myasthenia gravis. In stage one, of 15 pts recruited, 7 reported BOR of PR (47%) and another 11 patients were recruited into stage two. In total, 8 out of 26 patients achieved PR (BOR 31%; 95% CI 14.3% to 51.8%). Median duration of response (DOR) was 5.9 mths (95% CI 3.9 to 9.0). With a median follow up of 10.6 mths, median PFS was 5.3 mths (95% CI 2.8 to 6.4). Of EBVlo pts, 8 experienced a PR (53%; 95% CI 26.6% to 78.7%). No responses were observed in EBVhi pts. EBVlo pts had a median PFS of 6.8 mths (95% CI 2.8 to 10.4) compared to EBVhi 2.7 mths (95% CI 1.7 to 5.2). Conc