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

Date

09 Oct 2016

Session

Poster display

Presenters

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

Author affiliations

  • 1 Medical Oncology, 12 de Octubre University Hospital & Research Institute, 28041 - Madrid/ES
  • 2 Medical Oncology, Hospital Universitario Virgen Macarena, Sevilla/ES
  • 3 Medical Oncology, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 4 Radiation Oncology, Hospital Universitario Virgen Macarena, Sevilla/ES
  • 5 Radiation Oncology, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 6 Medical Oncology, Hospital General Universitario Valencia, Valencia/ES
  • 7 Radiation Oncology, Hospital General Universitario Valencia, Valencia/ES
  • 8 Medical Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 9 Medical Oncology, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 10 Radiation Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 11 Radiation Oncology, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 12 Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas/ES
  • 13 Radiation Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas/ES
  • 14 Radiation Oncology, 12 de Octubre University Hospital & Research Institute, 28041 - Madrid/ES
  • 15 Medical Oncology, Complejo Hospitalario Universitario de Santiago de Compostela SERGAS, Santiago de Compostela/ES
  • 16 Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, Barcelona/ES
  • 17 Radiation Oncology, Clinica Universitaria de Navarra, Pamplona/ES
  • 18 Radiation Oncology, Complejo Hospitalario Universitario de Santiago de Compostela SERGAS, Santiago de Compostela/ES
  • 19 Medical Oncology, Hospital Virgen de la Salud, Toledo/ES
  • 20 Medical Oncology, Clinica Universitaria de Navarra, Pamplona/ES
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Resources

Abstract 1943

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.

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