A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.

Abstract

480 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513 . Clinical trial information: NCT01462513.