Gray-B: an Open Label Multicenter Phase-2 Gem Study on Ipilimumab and Radiation in Patients with Melanoma and Brain Metastases

Estimated median overall survival (OS) in patients (pts) with brain metastases (BM) ranges between 1.8-10.5 months (mo). Ipilimumab (IPI) has shown activity against mel-BM. Radiation (RT) might be synergistic to anti-CTLA-4 blockade through an ‘abscopal’ effect. Open label single stage multicenter phase 2 study, assuming a historical 20% 1-year survival rate (1y SR) with RT. Target sample size: 56 evaluable pts. Target 1y SR: 35% (&agr;= 0.05, &bgr;= 0.2). Objectives: Primary: 1y SR; Secondary: progression free survival (PFS); OS; objective response rate (mWHO); safety and feasibility. Treatment: IPI 3 mg/Kg iv q 3 weeks (4 cycles); whole brain RT (WBRT) 30 Gy in 10 fractions (or equivalent), started between C1 and C2. Main eligibility: First episode of BM in mel pts; Karnofsky PS > 70%; Barthel Index > 10; RTOG-RPA class 2; measurable disease; LDH < 2 x ULN; not eligible for radical therapy; not experiencing rapid clinical deterioration; not requiring dexamethasone > 16 mg/d (or equivalent). This is a preliminary analysis after recruiting 43/56 pts (Apr 2014 - Mar 2016). Demographical characteristics are shown in the table.Tabled 1Age (median (range))65 (37-83)Gender (male; female)25; 18Karnofsky PS(100-90; 70-80)33; 8Barthel Index (>15; 10-15)35; 2BRAF mutation33% (11/33)Previous lines (0; 1; >1)22; 14; 7Previous BRAF/MEK inh9.3% (4/43)Brain mets (single; multiple; NA)8; 29; 6Liver mets10/43Corticosteroids at baseline/C132.4% Open table in a new tab Treatment exposure: IPI: 19 pts completed 4 cycles; RT: 3 pts had early termination. Efficacy: Estimated 1y SR: 31.4% (95%CI 14.0;48.8%), median OS 5.2 mo (95%CI 3.1;6.3); median PFS: 3.21 mo (95%CI 1.7;4.7). Safety: Serious AEs were reported for 23 pts (53.5%), 4 were treatment-related, G3 hepatic toxicity (IPI), G3 cephalalgia and vomiting (RT), G2 scalp erythema (RT) and G3 left hemiparesis. Treatment-related G3 toxicities were seen in 6 pts (14%): asthenia, skin rash, cephalalgia, emesis, hypothyroidism, liver toxicity, hemiparesia. A total of 22 pts died; none of the deaths were study-related. Concomitant IPI + WBRT is feasible. There were no unexpected safety issues. Despite the frequent need for costicosteroids at baseline, interim 1y SR is 31.4%. The trial is ongoing. Updated results will be presented.