ESTRO 2020 Abstract Book

S646 ESTRO 2020

France ; 2 Gustave Roussy Cancer Campus, Laboratory Of Immunomonitoring In Oncology- University Paris-saclay- Faculty Of Pharmacy, Villejuif, France ; 3 Gustave Roussy Cancer Campus, Biostatistic And Epidemiology Unit, Villejuif, France ; 4 Gustave Roussy Cancer Campus, Dermatology Unit- Department Of Medicine, Villejuif, France ; 5 Gustave Roussy Cancer Campus, Department Of Radiation Oncology, Villejuif, France ; 6 Gustave Roussy Cancer Campus- Fondazione IRCCS Policlinico San Matteo, Department Of Radiation Oncology, Villejuif, France ; 7 Gustave Roussy Cancer Campus, Outpatient Clinic- Department Of Medicine, Villejuif, France ; 8 Gustave Roussy Cancer Campus, Ditep, Villejuif, France ; 9 Gustave Roussy Cancer Campus, Department Of Radiology, Villejuif, France ; 10 Gustave Roussy Cancer Campus, Laboratory Of Immunomonitoring In Oncology, Villejuif, France ; 11 Medimmune, Medimmune, Gaithersburg, France ; 12 Gustave Roussy Cancer Campus, Dermatology Unit- University Paris-saclay- Faculty Of Medicine- Inserm Unit U981, Villejuif, France ; 13 Gustave Roussy Cancer Campus, Department Of Radiation Oncology- Radiomics Team- Molecular Radiotherapy Inserm U1030- University Paris-saclay- Faculty Of Medicine, Villejuif, France Purpose or Objective A synergy between radiotherapy (RT) and anti-CTLA-4 antibody has been demonstrated preclinically. The Mel-Ipi- Rx phase 1 study aimed to: i) determine the maximum tolerated dose (MTD) and safety profile of RT combined with ipilimumab (ipi) in patients (pts) with metastatic melanoma, and ii) assess the impact of ipi + RT systemic immune antitumor response (SIAR) and tumor growth rate (TGR) variation (ΔTGR) of irradiated (TGR irr ) and non- irradiated (TGR non-irr ) lesions. Material and Methods A 3+3 dose escalation design was used with 9, 15, 18 and 24 Gy dose of RT at week 4 combined with 10 mg/kg ipi every 3 weeks for 4 doses. The adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for AEs, version 4.0. Blood samples were collected at baseline, W4 (before 2nd ipi injection) and W6 (after ipi + RT) to phenotype T cells. TGR, defined as an increase in tumor volume during 1 month, was computed for TGR irr , and TGR non-irr in 2 periods: (i) Reference-TGR (REF-TGR) on baseline, and (ii) Experimental-TGR (EXP-TGR) between baseline and 1st evaluation. The ΔTGR between REF-TGR and EXP-TGR was used to assess the treatment effect. A negative value reflected a slowdown of disease progression. Results 19 pts received ipi between August 2011 and July 2015. Nine pts received the 4 doses of ipi. All pts received the combined RT. Grade 3 AEs occurred in 8 pts, the most common being colitis and hepatitis. No drug-related death occurred. DLT occurred in 2/6 pts in the cohort receiving 15 Gy. The MTD was 9 Gy dose. Two pts had complete response, 3 had partial response and 7 had stable disease, giving an objective response rate of 37%. Ipi alone could increase effector T cells (TEM), Treg and ICOS+ CD4+ T cells at W4. At W6, only TEM and ICOS+ CD4+ T cells significantly increased suggesting that combination could increase activated memory CD4+ T cells rather than Treg cells. CD8+ T cells did not increase at W4 while central memory T cells (TCM) and terminally differentiated (TEMRA) increased between W4 and W6, suggesting that RT + ipi could boost these CD8 + T populations. Increased CD8 from baseline to W4 was significantly correlated to progession-free survival (PFS) (p=0.0163). Interestingly, a higher effect of ipi+ RT seemed to be associated with a deeper ΔTGR non-irr than ΔTGR irr , although insignificant. The EXP-TGR non-irr was significantly associated with progressive disease.

Conclusion Concurrent RT and IT seems to be well tolerated with acceptable neurological adverse events. Stereotactic Radiation Therapy delivered concurrently with ICI may be associated with improved local control. However, these results need to be confirmed by prospective studies. PO-1227 A dose escalation phase 1 study of radiotherapy combined with ipilimumab in metastatic melanoma. C. Boutros 1 , N. Chaput 2 , E. Lanoy 3 , A. Larive 3 , C. Mateus 4 , E. Routier 4 , S. Roy 4 , R. Sun 5 , A. Lancia 6 , Y.G. Tao 5 , N. Ibrahim 7 , R. Khoury-Abboud 7 , C. Massard 8 , R. Bahleda 8 , D. Schwob 3 , C. Caramella 9 , L. Cassard 10 , J. Soria 11 , C. Robert 12 , E. Deutsch 13 1 Gustave Roussy Cancer Campus, Dermatology Unit- Outpatient Clinic- Department Of Medicine, Villejuif,