L-BLP25 treatment for advanced non-small cell lung cancer (NSCLC): Safety data from a phase IIb trial compared with an integrated safety analysis (ISA).

Abstract

e13058 Background: Safety data are not yet available for the potential long-term treatment of NSCLC with vaccines. In a phase IIB open-label, randomized trial, treatment with the therapeutic cancer vaccine L-BLP25 plus best supportive care (BSC) for stage IIIB and IV NSCLC improved median survival time over BSC alone (17.4 vs. 13.0 months, respectively). We report safety data for this trial and for an ISA of 5 completed trials for NSCLC (4 phase II, including the phase IIB trial, and 1 phase I) in which 153 patients (pts) received L-BLP25. Methods: In the phase IIB trial, pts were randomized to receive once-weekly doses of L-BLP25 (1000 μg sc) for 8 weeks, then L-BLP25 (1000 μg sc) at 6-week intervals plus BSC or BSC alone. Cyclophosphamide (CP) (300 mg/m2, iv single dose) was given 3 days before first L-BLP25 dose. All phase II trials used 1000 μg L-BLP25 primary doses, and either 1000 or 250 μg maintenance doses. The phase I trial compared 20 and 200 μg L- BLP25 primary and maintenance doses. Results: The frequencies of most adverse events (AEs) were comparable for the two treatment arms of the phase IIB trial (Table). However, ≥10% differences were observed between the treatment arms for AEs representing injection-site reactions (ISRs), flu-like symptoms, and rash. The most frequent AEs in both arms of the phase IIB trial and the ISA were those typical of underlying NSCLC or attributable to flu-like symptoms. Gastrointestinal AEs were common, with nausea for L-BLP25-treated pts primarily CP-related. The frequency of ISRs was similar for L-BLP25-treated pts in the phase IIB trial and the ISA. Serious AEs were reported for fewer pts in the L-BLP25 arm (33%) than the BSC arm (41%) in the phase IIB trial, and for 33% of pts in the ISA. Conclusions: Safety data from the phase IIB trial were comparable with the ISA data and confirmed a favorable safety profile for L-BLP25 in NSCLC. AEs with ≥25% incidence in either the phase IIB trial or the ISA AE (%) Phase IIB trial ISA BSC(n = 83) L-BLP25 + BSC(n = 88) L-BLP25(n = 153) Any 96 100 100 Cough 35 52 47 Fatigue 43 51 44 Nausea 41 50 54 Dyspnea 39 39 36 Anorexia 30 34 25 Back pain 19 31 25 Chest pain 19 31 25 Injection site erythema - 25 25 Headache 25 24 33 Arthralgia 19 20 25 Nodule - 16 25 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA Merck Serono Merck KGaA Merck, Merck Serono EMD Serono