A Randomized Phase II Study of Anti-CSF1 Monoclonal Antibody Lacnotuzumab (MCS110) Combined with Gemcitabine and Carboplatin in Advanced Triple-Negative Breast Cancer.

Abstract

This phase II study determined the efficacy of lacnotuzumab added to gemcitabine plus carboplatin (gem-carbo) in patients with advanced triple-negative breast cancer (TNBC). Female patients with advanced TNBC, with high levels of tumor-associated macrophages not amenable to curative treatment by surgery or radiotherapy were enrolled. Lacnotuzumab was dosed at 10 mg/kg every 3 weeks, ± a dose on cycle 1, day 8. Gemcitabine (1,000 mg/m²) and carboplatin (dose in mg calculated by area under the curve [mg/mL/min] × (glomerular filtration rate [mL/min] + 25 [mL/min]) were dosed every 3 weeks. Treatment continued until unacceptable toxicity, disease progression, or discontinuation by physician/patient. Patients received lacnotuzumab + gem-carbo (<i>n</i> = 34) or gem-carbo (<i>n</i> = 15). Enrollment was halted due to recruitment challenges owing to rapid evolution of the therapeutic landscape; formal hypothesis testing of the primary endpoint was therefore not performed. Median progression-free survival was 5.6 months [90% confidence interval (CI), 4.47-8.64] in the lacnotuzumab + gem-carbo arm and 5.5 months (90% CI, 3.45-7.46) in the gem-carbo arm. Hematologic adverse events were common in both treatment arms; however, patients treated with lacnotuzumab experienced more frequent aspartate aminotransferase, alanine aminotransferase, and creatine kinase elevations. Pharmacokinetic results showed that free lacnotuzumab at 10 mg/kg exhibited a typical IgG pharmacokinetic profile and target engagement of circulating colony-stimulating factor 1 ligand. Despite successful target engagement and anticipated pharmacokinetic profile, lacnotuzumab + gem-carbo showed comparable antitumor activity to gem-carbo alone, with slightly poorer tolerability. However, the data presented in this article would be informative for future studies testing agents targeting the CSF1-CSF1 receptor pathway in TNBC.