ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients

ABSTRACT Background Lymphopenia is a predictive factor for hematological toxicity, progression and early death in advanced cancers including metastatic breast cancer (MBC). CYT107 is a recombinant interleukin 7 (IL-7) (Cytheris, now Revimmune), well tolerated and able to expand lymphocyte pool in humans. The aims of this study were to determine the optimal schedule to deliver CYT107 and to assess its effect on clinical end points. Patient and methods This placebo-controlled, double blind, phase IIa was conducted in MBC patients with Results When administered before chemotherapy, CYT107 induced a significant increase of CD4+ [+148.1% in CYT107 versus +9.9% in placebo groups, (Wilcoxon, P = 0.002)] and CD8+ T-cell counts, including both naive and memory subsets. When CYT107 was administered during chemotherapy, the magnitude of CD4+ and CD8+ increase was less important. No modulation of immune cell functional competence was observed. CYT107 was well tolerated with no related ≥grade 3 adverse events except 1 fatal suspected unexpected serious adverse reaction (SUSAR) of uncertain relationship. Of the 12 cases evaluable for response, 6 of 7 patients (86%) receiving CYT107 before chemotherapy achieved a response or stabilization, whereas two of five patients (40%) receiving placebo achieved the same result. No significant difference was observed for PFS or OS. Conclusion In lymphopenic MBC, CYT107 increases CD4+ and other T-cell subset counts without altering their function. A larger clinical trial to demonstrate its impact on clinical outcome is warranted. ClinicalTrials.gov Identifier NCT01362107.