1118P - GRAY-B: An open label multicenter phase-2 GEM study on ipilimumab and radiation in patients with melanoma and brain metastases

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Skin cancers
Melanoma
Presenter Jose Lopez Martin
Citation Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379
Authors J.A. Lopez Martin1, L. de la Cruz Merino2, A.M. Arance Fernandez3, A. Illescas4, I. Valduviecu Ruiz5, A. Berrocal6, J. Lopez-Torrecilla7, I. Marquez Rodas8, M.V. Soriano Teruel9, A. Alvarez Gonzalez10, M.L. Chust Vicente11, D. Rodriguez Abreu12, R. Cabrera13, M.C. Penas Sanchez14, T. Curiel15, E. Munoz Couselo16, J.J. Aristu17, A. Gomez-Caamano18, J. Medina Martinez19, S. Martin-Algarra20
  • 1Medical Oncology, 12 de Octubre University Hospital & Research Institute, 28041 - Madrid/ES
  • 2Medical Oncology, Hospital Universitario Virgen Macarena, Sevilla/ES
  • 3Medical Oncology, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 4Radiation Oncology, Hospital Universitario Virgen Macarena, Sevilla/ES
  • 5Radiation Oncology, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 6Medical Oncology, Hospital General Universitario Valencia, Valencia/ES
  • 7Radiation Oncology, Hospital General Universitario Valencia, Valencia/ES
  • 8Medical Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 9Medical Oncology, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 10Radiation Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 11Radiation Oncology, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 12Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas/ES
  • 13Radiation Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas/ES
  • 14Radiation Oncology, 12 de Octubre University Hospital & Research Institute, 28041 - Madrid/ES
  • 15Medical Oncology, Complejo Hospitalario Universitario de Santiago de Compostela SERGAS, Santiago de Compostela/ES
  • 16Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, Barcelona/ES
  • 17Radiation Oncology, Clinica Universitaria de Navarra, Pamplona/ES
  • 18Radiation Oncology, Complejo Hospitalario Universitario de Santiago de Compostela SERGAS, Santiago de Compostela/ES
  • 19Medical Oncology, Hospital Virgen de la Salud, Toledo/ES
  • 20Medical Oncology, Clinica Universitaria de Navarra, Pamplona/ES

Abstract

Background

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.

Methods

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% (α= 0.05, ß= 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  16 mg/d (or equivalent).

Results

This is a preliminary analysis after recruiting 43/56 pts (Apr 2014 - Mar 2016). Demographical characteristics are shown in the table.

Age (median (range)) 65 (37-83)
Gender (male; female) 25; 18
Karnofsky PS(100-90; 70-80) 33; 8
Barthel Index (>15; 10-15) 35; 2
BRAF mutation 33% (11/33)
Previous lines (0; 1; >1) 22; 14; 7
Previous BRAF/MEK inh 9.3% (4/43)
Brain mets (single; multiple; NA) 8; 29; 6
Liver mets 10/43
Corticosteroids at baseline/C1 32.4%
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.

Conclusions

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.

Clinical trial identification

EudraCT 2013-001132-22

Legal entity responsible for the study

GEM (Grupo Español de Melanoma / Melanoma Spanish Group)

Funding

BMS

Disclosure

J.A. Lopez Martin: BMS: research grant, Advisory Board MSD: research grant, advisory board Roche: research grant Novartis: research grant. I. Marquez Rodas: Advisory role: BMS honoraria and travel accomodation: BMS. S. Martin-Algarra: BMS: Advisory Board, paid lectures. All other authors have declared no conflicts of interest.