Elypse-7: A Randomized, Placebo-Controlled, Phase 2a Evaluating The Impact Of Il-7 Immunotherapy On Cd4 Count, Risks Of Severe Haematological Toxicity And Tumor Progression In Metastatic Breast Cancer Patients

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Total and CD4 lymphopenia is observed in 25% of advanced cancers patients and is a predictive factor of chemotherapy (CT)-induced death, febrile neutropenia, thrombocytopenia, anemia, as well as an independent prognostic factor for survival and tumor progression. CYT107 is a glycosylated recombinant human IL-7 (CYTHERIS, France) emerging as a promising immuno-restorative agent well tolerated in Phase 1 trials. To date, it is unknown whether IL-7 can correct lymphopenia during CT and whether this could translate into clinical benefit in advanced cancer patients. Methods: A placebo-controlled, monocentric, Phase 2a ([NCT01368107][1]) was conducted in lymphopenic metastatic breast cancer (MBC) patients to be treated by capecitabine (2500mg/m2/d, pers os, 21-day cycle from D21 after randomization). Using a 2x2 factorial design, patients were randomly allocated to 4 arms to receive 1) before the 1st cycle of CT : r-hIL-7 (CYT107:10µg/kg, subcutaneously, weekly at D0, D7, D14, groups 2 & 4) or placebo (groups 1 & 3), then 2) during the 3rd cycle of CT: r-hIL-7 (weekly at D57, D64, D71, groups 3 & 4) or placebo (groups 1 & 2). The primary endpoint, CD4 count evolution, was evaluated before (D0 to D21) and during CT (D57 to D78). Secondary endpoints include risks of severe hematological AE, safety and progression free survival (PFS). An ancillary study has evaluated the quantitative and functional changes in circulating immune cells (see abstract Menetrier-Caux). Results: From Nov. 2011 to Jun. 2013, 20 patients (median age [range]: 60 [39-76 y.]; median CD4 count on D0: 242 [22-522 cells/µL]) with MBC (mainly with bone and liver metastasis) were enrolled. Before CT (n=20), r-hIL-7 treatment induced a significant increase of CD4 count (median relative evolution: +148.1% [41.8-763.9 cells/µL] in r-hIL-7 groups vs +9.9% [-50.3-102.2 cells/µL] in placebo [Wilcoxon, p=0.002]). During CT (n=11), r-hIL-7 treatment also increased CD4 count (+58.6%[-15.2-281.5 cells/µL] in r-hIL-7 groups vs -2.4% [-27.6-112.5 cells/µL] in placebo [p=0.121]). Overall, r-hIL-7 was well tolerated with reactions related to injection as the main specific AE, no binding or neutralizing antibodies, and no r-hIL-7-related ≥ Grade 3 AE except 1 fatal SAE for which one a relationship to r-hIL-7 cannot be ruled out. Interestingly, r-hIL-7 treatment during CT reduced the incidence of Grade 3 hematological AE compared to placebo (0 vs 5 events, respectively). PFS data will be available by Feb. 2014. Conclusion: In this exploratory trial, r-hIL-7 treatment was safe at biologically active dose, able to correct CD4 lymphopenia and associated with lower incidence of severe hematological toxicity during CT. These early results are encouraging and warrant further investigations of IL-7 clinical applications in the oncology field. Citation Format: Ray-Coquard Isabelle, Olivier Tredan, Gwenaele Garin, Christine Menetrier-Caux, Sylvie Chabaud, Thomas Bachelot, Claire Cropet, Pierre-Etienne Heudel, Paul Rebattu, Patricia Dupont, Estelle Verronese, Anne-claire Cadore, Valerie Fouillat, Olfa Derbel, Nathalie Bonnin, Therese Croughs, Michel Morre, Nicolas Pasqual, Manuari Manuel, Gilles Clapisson, Christophe Caux, David Perol, Jean-Yves Blay. Elypse-7: A randomized, placebo-controlled, Phase 2a evaluating the impact of IL-7 immunotherapy on CD4 count, risks of severe haematological toxicity and tumor progression in metastatic breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT333. doi:10.1158/1538-7445.AM2014-CT333 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01368107&atom=%2Fcanres%2F74%2F19_Supplement%2FCT333.atom