A Randomized Phase II Study of Anti-CSF1 Monoclonal Antibody Lacnotuzumab (MCS110) Combined with Gemcitabine and Carboplatin in Advanced Triple-Negative Breast Cancer
Journal
Clinical Cancer Research
Journal Volume
28
Journal Issue
1
Pages
106-115
Date Issued
2022
Author(s)
Kuemmel S.
Campone M.
Loirat D.
Lopez R.L.
Thaddeus Beck J.
de Laurentiis M.
Im S.-A.
Kim S.-B.
Kwong A.
Steger G.G.
Adelantado E.Z.
Duhoux F.P.
Greil R.
Kuter I.
Tibau A.
?zg?ro?lu M.
Scholz C.W.
Singer C.F.
Vega E.
Wimberger P.
Zamagni C.
Couillebault X.-M.
Fan L.
Guerreiro N.
Mataraza J.
Sand-Dejmek J.
Chan A.
Abstract
PURPOSE: 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). PATIENTS AND METHODS: ) 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. RESULTS: = 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. CONCLUSIONS: 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.
SDGs
Publisher
American Association for Cancer Research Inc.
Type
journal article