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Combination immunotherapy with nivolumab and ipilimumab in patients with rare gynecological malignancies: results of the CA209-538 clinical trial

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posted on 2022-01-04, 22:44 authored by O Klein, D Kee, B Gao, B Markman, Jessica da Gama DuarteJessica da Gama Duarte, Luke Quigley, L Jackett, R Linklater, A Strickland, C Scott, L Mileshkin, J Palmer, M Carlino, Andreas BehrenAndreas Behren, Jonathan CebonJonathan Cebon
Background 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. Methods 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). Results 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. Conclusions 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.


The study received funding and drug support from Bristol Myers Squibb. Funding support was also provided in part by a grant from the Commonwealth of Australia, Department of Health Accelerated Research Program. AB was supported by a fellowship from the Department of Health and Human Services acting through the Victorian Cancer Agency. JdGD was supported by Cure Cancer Australia through the Cancer Australia Priority--driven Cancer Research Scheme (grant 1187815).


Publication Date



Journal for ImmunoTherapy of Cancer



Article Number



9p. (p. 1-9)





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