Kuemmel, Sherko, Campone, Mario, Loirat, Delphine, Lopez Lopez, Rafael, Beck, J.Thaddeus , De Laurentiis, Michelino, Im, Seock-Ah, Kim, Sung-Bae, Kwong, Ava, Steger, Guenther G, Adelantado, Esther Zamora, Duhoux, Francois P, Greil, Richard, Kuter, Irene, Lu, Yen-Shen, Tibau, Ariadna, Özgüroğlu, Mustafa, Scholz, Christian, Singer, Christian F. , Vega, Estela, Wimberger, Pauline, Zamagni, Claudio, Couillebault, Xuan-Mai, Fan, Liqiong, Guerreiro, Nelson, Mataraza, Jennifer, Sand Dejmek, Janna and Chan , Arlene (2021) A Randomized Phase II Study of Anti-CSF-1 Monoclonal Antibody Lacnotuzumab (MCS110) Combined with Gemcitabine and Carboplatin in Advanced Triple Negative Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. ISSN 1557-3265

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, and not amenable to curative treatment by surgery or radiotherapy, were enrolled. Lacnotuzumab was dosed at 10 mg/kg every 3 weeks (Q3W), {plus minus} a dose on Cycle 1, Day 8. Gem and carbo were given at 1000 mg/m2 and area under curve 2 dose in mg, respectively, Q3W. Treatment continued until unacceptable toxicity, disease progression, or discontinuation by physician/patient.Patients received lacnotuzumab+gem-carbo (n=34) or gem-carbo (n=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% 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 CSF-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 manuscript would be informative for future studies testing agents targeting the CSF-1-CSF-1R pathway in TNBC.

Item Type:	Article
Date Deposited:	08 Dec 2021 00:45
Last Modified:	08 Dec 2021 00:45
URI:	https://oak.novartis.com/id/eprint/41746