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Title: Combination immunotherapy with nivolumab and ipilimumab in patients with rare gynecological malignancies: results of the CA209-538 clinical trial.
Austin Authors: Klein, Oliver ;Kee, Damien ;Gao, Bo;Markman, Ben;da Gama Duarte, Jessica;Quigley, Luke;Jackett, Louise A ;Linklater, Richelle;Strickland, Andrew;Scott, Clare;Mileshkin, Linda;Palmer, Jodie ;Carlino, Matteo;Behren, Andreas;Cebon, Jonathan S 
Affiliation: Medical Oncology
Olivia Newton-John Cancer Research Institute
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Anatomical Pathology
Medicine (University of Melbourne)
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Blacktown Hospital and the University of Sydney, Sydney, New South Wales, Australia
Department of Medical Oncology, Monash Health, Melbourne, Victoria, Australia
Monash University, Melbourne, Victoria, Australia
Issue Date: Nov-2021
Publication information: Journal for Immunotherapy of Cancer 2021; 9(11): e003156
Abstract: Patients with rare cancers represent 55% of all gynecological malignancies and have poor survival outcomes due to limited treatment options. Combination immunotherapy with the anti-programmed cell death protein 1 (anti-PD-1) antibody nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab has demonstrated significant clinical efficacy across a range of common malignancies, justifying evaluation of this combination in rare gynecological cancers. This multicenter phase II study enrolled 43 patients with advanced rare gynecological cancers. Patients received induction treatment with nivolumab and ipilimumab at a dose of 3 mg/kg and 1 mg/kg, respectively, every 3 weeks for four doses. Treatment was continued with nivolumab monotherapy at 3 mg/kg every 2 weeks until disease progression or a maximum of 2 years. The primary endpoint was the proportion of patients with disease control at week 12 (complete response, partial response or stable disease (SD) by Response Evaluation Criteria In Solid Tumor V.1.1). Exploratory evaluations correlated clinical outcomes with tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). The objective response rate in the radiologically evaluable population was 36% (12/33 patients) and in the intention-to-treat population was 28% (12/43 patients), with additional 7 patients obtaining SD leading to a disease control rate of 58% and 44%, respectively. Durable responses were seen across a range of tumor histologies. Thirty-one (72%) patients experienced an immune-related adverse event (irAE) with a grade 3/4 irAE observed in seven (16%) patients. Response rate was higher among those patients with baseline PD-L1 expression (≥1% on tumor cells) but was independent of TMB. Ipilimumab and nivolumab combination treatment has significant clinical activity with a favorable safety profile across a range of advanced rare gynecological malignancies and warrants further investigation in these tumor types.
DOI: 10.1136/jitc-2021-003156
ORCID: 0000-0003-0022-9553
Journal: Journal for Immunotherapy of Cancer
PubMed URL: 34782426
PubMed URL:
Type: Journal Article
Subjects: CTLA-4 antigen
programmed cell death 1 receptor
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