Philippe A Cassier1, Antoine Italiano2, Carlos Gomez-Roca3, Christophe Le Tourneau4, Maud Toulmonde2, Sandra P D'Angelo5, Kristy Weber6, Delphine Loirat7, Wolfgang Jacob8, Anna-Maria Jegg9, Francesca Michielin10, Randolph Christen10, Carl Watson11, Michael Cannarile9, Irina Klaman9, Keelara Abiraj10, Carola H Ries9, Martin Weisser9, Dominik Rüttinger9, Jean-Yves Blay12, Jean-Pierre Delord3. 1. Centre Léon Bérard, Département D'Oncologie Médicale, Lyon, France. 2. Institut Bergonie, Oncologie, Bordeaux, France. 3. Institut Claudius Regaud, Département D'Oncologie Médicale, Toulouse, France. 4. Department of Drug Development and Innovation (D3i), Institut Curie, Paris & Saint-Cloud, France; INSERM U900 Research Unit, Saint-Cloud, France; Paris-Saclay University, Paris, France. 5. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA. 6. University of Pennsylvania, Philadelphia, USA. 7. Department of Drug Development and Innovation (D3i), Institut Curie, Paris & Saint-Cloud, France. 8. Pharma Research and Early Development (pRED), Roche Innovation Center Munich, Penzberg, Germany. Electronic address: wolfgang.jacob@roche.com. 9. Pharma Research and Early Development (pRED), Roche Innovation Center Munich, Penzberg, Germany. 10. Pharma Research and Early Development (pRED), Roche Innovation Center Basel, Basel, Switzerland. 11. A4P Ltd, Sandwich, UK. 12. Centre Léon Bérard, Département D'Oncologie Médicale, Lyon, France; Université Claude Bernard Lyon I, Lyon, France; Unicancer, Paris, France.
Abstract
OBJECTIVES: This study investigated the safety, clinical activity and patient-reported outcomes of patients with diffuse-type tenosynovial giant-cell tumour (dTGCT) of the soft tissue who were treated with emactuzumab, a humanised anti-colony stimulating factor 1 receptor (CSF1R) monoclonal antibody and were followed up for up to 2 years after the start of treatment. METHODS: In this open-label phase 1 study (ClinicalTrials.govNCT01494688), patients received intravenous (IV) emactuzumab from 900 to 2000 mg every two weeks in the dose-escalation phase and at the optimal biological dose of 1000 mg with different schedules in the dose-expansion phase. Adverse event (AE) rates and biomarker assessments from tumour biopsies were analysed. Quality of life was assessed using a standard questionnaire (EuroQol-5D-3L) and the WOMAC® 3.1 Osteoarthritis Index. Tumour responses were determined with magnetic resonance imaging. RESULTS: Altogether, 63 patients were enrolled into the study. The most frequently reported AEs were pruritus, asthenia and oedema. In 36 patients for whom biopsy tissue was available a substantial decrease of CSF1R-positive and CD68/CD163-positive macrophages was detected. The independently reviewed best overall objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors version 1.1) was 71%. Responses were durable, and an ORR of 70% and 64% was determined after one or two years after enrolment into the study. Clinical activity was accompanied by an improvement in EuroQol-5D-3L and particularly the joint disorder-specific WOMAC score. CONCLUSIONS: Systemic therapy of dTGCT patients with emactuzumab resulted in pronounced and durable responses associated with symptomatic improvement and a manageable safety profile.
OBJECTIVES: This study investigated the safety, clinical activity and patient-reported outcomes of patients with diffuse-type tenosynovial giant-cell tumour (dTGCT) of the soft tissue who were treated with emactuzumab, a humanised anti-colony stimulating factor 1 receptor (CSF1R) monoclonal antibody and were followed up for up to 2 years after the start of treatment. METHODS: In this open-label phase 1 study (ClinicalTrials.govNCT01494688), patients received intravenous (IV) emactuzumab from 900 to 2000 mg every two weeks in the dose-escalation phase and at the optimal biological dose of 1000 mg with different schedules in the dose-expansion phase. Adverse event (AE) rates and biomarker assessments from tumour biopsies were analysed. Quality of life was assessed using a standard questionnaire (EuroQol-5D-3L) and the WOMAC® 3.1 Osteoarthritis Index. Tumour responses were determined with magnetic resonance imaging. RESULTS: Altogether, 63 patients were enrolled into the study. The most frequently reported AEs were pruritus, asthenia and oedema. In 36 patients for whom biopsy tissue was available a substantial decrease of CSF1R-positive and CD68/CD163-positive macrophages was detected. The independently reviewed best overall objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors version 1.1) was 71%. Responses were durable, and an ORR of 70% and 64% was determined after one or two years after enrolment into the study. Clinical activity was accompanied by an improvement in EuroQol-5D-3L and particularly the joint disorder-specific WOMAC score. CONCLUSIONS: Systemic therapy of dTGCT patients with emactuzumab resulted in pronounced and durable responses associated with symptomatic improvement and a manageable safety profile.
Authors: Carlos Gomez-Roca; Philippe Cassier; Dmitriy Zamarin; Jean-Pascal Machiels; Jose Luis Perez Gracia; F Stephen Hodi; Alvaro Taus; Maria Martinez Garcia; Valentina Boni; Joseph P Eder; Navid Hafez; Ryan Sullivan; David Mcdermott; Stephane Champiat; Sandrine Aspeslagh; Catherine Terret; Anna-Maria Jegg; Wolfgang Jacob; Michael A Cannarile; Carola Ries; Konstanty Korski; Francesca Michielin; Randolph Christen; Galina Babitzki; Carl Watson; Georgina Meneses-Lorente; Martin Weisser; Dominik Rüttinger; Jean-Pierre Delord; Aurelien Marabelle Journal: J Immunother Cancer Date: 2022-05 Impact factor: 12.469