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

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

  • Clin Cancer Res. 2022 Jan 1;28(1):106-115. doi: 10.1158/1078-0432.CCR-20-3955.
Sherko Kuemmel 1,  Mario Campone 2,  Delphine Loirat 3,  Rafael Lopez Lopez 4,  J Thaddeus Beck 5,  Michelino De Laurentiis 6,  Seock-Ah Im 7,  Sung-Bae Kim 8,  Ava Kwong 9,  Guenther G Steger 10,  Esther Zamora Adelantado 11,  Francois P Duhoux 12,  Richard Greil 13,  Irene Kuter 14,  Yen-Shen Lu 15,  Ariadna Tibau 16,  Mustafa Özgüroğlu 17,  Christian W Scholz 18,  Christian F Singer 19,  Estela Vega 20,  Pauline Wimberger 21,  Claudio Zamagni 22,  Xuan-Mai Couillebault 23,  Liqiong Fan 24,  Nelson Guerreiro 23,  Jennifer Mataraza 24,  Janna Sand-Dejmek 23,  Arlene Chan 25
Affiliations

Affiliations

  • 1 Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Essen, Germany. s.kuemmel@kem-med.com.
  • 2 Institut de Cancérologie de l'Ouest-Centre René Gauducheau, St Herblain, France.
  • 3 Medical Oncology Department and D3i, Institut Curie, Paris, France.
  • 4 Clinical University Hospital & Health Research Institute of Santiago de Compostela-CIBERONC, Santiago de Compostela, Spain.
  • 5 Highlands Oncology Group, Fayetteville, Massachusetts.
  • 6 Istituto Nazionale dei Tumori IRCCS "Fondazione Pascale", Napoli, Italy.
  • 7 Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 8 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 9 Queen Mary Hospital, The University of Hong Kong, Hong Kong.
  • 10 Department of Internal Medicine I, Division of Oncology and Gaston H. Glock Research Center, Medical University of Vienna, Vienna, Austria.
  • 11 Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
  • 12 King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
  • 13 Paracelsus Medical University, Salzburg Cancer Research Institute-CCCIT and Cancer Cluster Salzburg, Salzburg, Austria.
  • 14 Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
  • 15 National Taiwan University Hospital, Taipei, Taiwan.
  • 16 Oncology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau and Universitat Autònoma de Barcelona, Barcelona, Spain.
  • 17 Istanbul University - Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey.
  • 18 Vivantes Klinikum Am Urban, Berlin, Germany.
  • 19 Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
  • 20 CIOCC-Grupo Hospitalario de Madrid, Madrid, Spain.
  • 21 Carl Gustav Carus University, TU Dresden, Dresden, Germany.
  • 22 Osp.di bologna, Bologna, Italy.
  • 23 Novartis Pharma AG, Basel, Switzerland.
  • 24 Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
  • 25 Breast Cancer Research Centre-WA & Curtin University, Perth, Western Australia, Australia.
PMID: 34615719 DOI: 10.1158/1078-0432.CCR-20-3955
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: 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.

Results: 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% 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.

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