Abstract 1069P
Background
Solid pediatric tumors that appear in adulthood are a heterogeneous group that share some characteristics such as low incidence, lack of standard therapeutic options and reduced survival. We conducted the first phase II clinical trial of nivolumab and ipilimumab in this setting.
Methods
This is a multicenter, open-label, single arm phase II study to evaluate efficacy, safety and tolerability of the combination of nivolumab and ipilimumab in adult patients (18 years) with locally advanced or metastatic childhood malignancies that have progressed or are not candidates to standard therapy. Treatment: nivolumab 3 mg/kg IV q2w + ipilimumab 1 mg/kg IV q6w for 6 months or until progression/unacceptable toxicity. Primary endpoint: disease control rate (DCR) according to RECIST v1.1 criteria: complete response (CR) + partial response (PR) + stable disease (SD). Secondary endpoints: overall response rate (ORR), progression free survival (PFS) and overall survival (OS). A translational molecular biomarker research is ongoing.
Results
82 patients were enrolled between 7/03/2017 and 12/13/2019, 13 screen failure. Intention to treat population (ITT) was 69. Mean age: 42y (range 18-75). 58% were male and 94,1% Caucasian. Most frequent histologies: medulloblastoma (11,6%), Ewing family tumors (10,1%) and neuroblastoma (8,7%). 89,7% received prior systemic therapy and 38,2% had progression disease as best response to prior treatment. Mean number of previous treatment lines: 2,7 (range 1-9). 57 patients ECOG 0-1, and 12 ECOG 2. DCR was 41,7% in evaluable patients, and 36,2% in ITT. 1 neuroblastoma patient achieved CR with a DoR of 25,72m, 2 patients PR and 22 SD. With a median follow up of 5,7 months, median PFS and OS were 2,1 (95% CI 1,75-2,44) and 8,4 months (95% CI 5-11,79). 6 months-PFS was 28% (95% CI 17-39). Neuroblastoma patients had better OS (29,3 m; p=0,005). 38 (55,1%) patients had at least one related adverse event (AE) of any grade, 16 (23,2%) grade 3/4. Only 4 (5,8%) discontinued treatment for AEs.
Conclusions
Nivolumab and ipilimumab combo offered an effective and well-tollerated treatment option for some patients with these rare cancers without other choice, even in a poor prognosis setting (very pretreated and resistant).
Clinical trial identification
EudraCT Number: 2016-003946-99.
Editorial acknowledgement
No editorial assistance.
Legal entity responsible for the study
GETHI: Spanish Group of Rare and Orphan Tumors.
Funding
BMS.
Disclosure
X. Mielgo Rubio: Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS. All other authors have declared no conflicts of interest.