Phase II Trial of a Peptide Vaccine, Ocv-501 in Elderly Patients with Acute Myeloid Leukemia

Introduction: In recent decades, a considerable number of tumor antigens have been characterized, including the leukemia-associated antigen, Wilm's tumor 1 (WT1). WT1 is found to be expressed at low levels in various normal tissues such as gonads, kidney and the hematopoietic system. However, it is highly overexpressed in various hematological malignancies and solid tumors, including in the majority of acute myeloid leukemia (AML) cases. OCV-501 is a human leukocyte antigen (HLA) class II-restricted helper peptide derived from the WT1 protein. This Phase II trial was conducted to evaluate the efficacy and safety of OCV-501 in elderly patients with AML (ClinicalTrials.gov identifier: NCT01961882).

Methods: This multicenter, randomized, double-blind, placebo-controlled trial was conducted in Japan, the Republic of Korea and Taiwan between October, 2013 to November, 2017. The key eligibility criteria for this trial were patients with AML, aged 60 years or older, who achieved first complete remission within one or two courses of standard induction therapy, completed more than one course of standard consolidation therapy, and not scheduled for hematopoietic stem cell transplantation. Patients were assigned to receive either OCV-501 monotherapy or placebo. Subcutaneous administration of OCV-501 3mg or placebo was given once weekly up to the eighth administration, and once biweekly from the ninth administration onwards up to a duration of 2 years, followed by post-treatment observation period. The primary endpoint was disease-free survival (DFS) that was defined as the time from randomization to AML relapse or death from any cause, whichever came first, within the observation period. Secondary endpoints were overall survival (OS), quality of life (QOL; The European Organization for Research and Treatment of cancer [EORTC] QLQ-C30), and performance status (Eastern Cooperative Oncology Group performance status [ECOG PS]). Safety, including any occurrence of adverse events (AEs) was evaluated.

Results: A total of 133 patients who had achieved first remission after prior induction and consolidation therapies were randomized to receive either OCV-501 (OCV-501 arm, N=68) or placebo (placebo arm, N=65). The median age of the patients was 67 years (range, 60 - 85) and most of them had good performance status (ECOG PS score 0 - 1). The WT1 mRNA level at Day 1 was <50 copies/μg RNA in 37 patients in the OCV-501 arm and 28 patients in the placebo arm. In the evaluation of efficacy, there was no significant difference in DFS between both arms, and the median DFS was 12.1 months and 8.4 months in the OCV-501 arm and placebo arm, respectively. The median OS was 38.5 months and 31 months in the OCV-501 arm and placebo arm, respectively. The results of patient QOL and PS were similar between both arms. Overall, there were no significant safety findings throughout the trial. A majority of the patients in both arms had at least 1 treatment-emergent AE (TEAE); however, most of the TEAEs were mild in severity (Grade 1 or 2). The most frequently reported TEAE was site injection induration.

Conclusion: There was no significant difference in DFS between OCV-501- and placebo-treated patients. OCV-501 was found to be generally safe and well-tolerated in elderly AML patients.