Current Trial Report|Articles in Press

Study design and rationale for Marble Study: A phase II trial of atezolizumab (MPDL3280A) plus carboplatin and paclitaxel in patients with advanced or recurrent thymic carcinoma (JTD2101)



      Thymic carcinoma (TC) is a rare thymic epithelial tumor, and advanced or recurrent TC has limited prognosis. Treatment for chemotherapy-naïve, advanced, or recurrent TC remains unchanged with the combination of carboplatin and paclitaxel; therefore, a new treatment strategy is warranted. Immune checkpoint blockades inhibiting the programmed cell death-1 (PD-1) pathway (PD-1 and its ligand, PD-L1) have shown potential as a monotherapy for TC, although the efficacy of monotherapy was moderate for previously treated TC. We hypothesized that the combination of an anti-PD-L1 antibody, atezolizumab, with carboplatin and paclitaxel, would be effective in inducing immunogenic cell death in patients with advanced or recurrent TC.


      We initiated a multicenter, single-arm, open-label phase II study of atezolizumab combined with carboplatin and paclitaxel for metastatic or recurrent TC. Eligible patients will receive atezolizumab plus carboplatin and paclitaxel every three weeks for up to six cycles, followed by atezolizumab every three weeks for up to two years until progression or unacceptable toxicity. A total of 47 patients will be enrolled in this study, with a 24-month enrollment period and 12-month follow-up. The primary endpoint is the objective response rate (ORR), based on an independent central review. The secondary endpoints are the investigator-assessed ORR, disease control rate, progression-free survival, duration of response, overall survival, and safety.


      This study aims to establish the safety and efficacy of atezolizumab combined with carboplatin and paclitaxel in patients with advanced or recurrent TC.

      Trial registration

      Japan Registry of Clinical Trials (jRCT), jRCT2031220144. Registered on June 18, 2022,



      AUC (Area under the curve), CI (Confidence interval), ECOG (Eastern Cooperative Oncology Group), HR (Hazard ratio), ICI (Immune checkpoint inhibitor), ICR (Independent central review), INV (Investigator-assessed), jRCT (Japan Registry of Clinical Trials), ORR (Objective response rate), OS (Overall survival), PD-1 (Programmed cell death-1), PD-L1 (Programmed cell death ligand-1), PFS (Progression-free survival), PS (Performance status), TC (Thymic carcinoma), TET (Thymic epithelial tumor)
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        • Engels EA
        • Pfeiffer RM.
        Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies.
        Int J Cancer. 2003; 105: 546-551
        • Marx A
        • Chan JKC
        • Chalabreysse L
        • et al.
        The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial, Germ Cell, and Mesenchymal Tumors?.
        J Thorac Oncol. 2022; 17: 200-213
        • Ruffini E
        • Detterbeck F
        • Van Raemdonck D
        • et al.
        Thymic carcinoma: a cohort study of patients from the European society of thoracic surgeons database.
        J Thorac Oncol. 2014; 9: 541-548
        • Ahmad U
        • Yao X
        • Detterbeck F
        • et al.
        Thymic carcinoma outcomes and prognosis: results of an international analysis.
        J Thorac Cardiovasc Surg. 2015; 149 (101.e101-102): 95-100
        • Kondo K
        • Monden Y.
        Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan.
        Ann Thorac Surg. 2003; 76 (discussion 884-875): 878-884
        • Weksler B
        • Dhupar R
        • Parikh V
        • Nason KS
        • Pennathur A
        • Ferson PF.
        Thymic carcinoma: a multivariate analysis of factors predictive of survival in 290 patients.
        Ann Thorac Surg. 2013; 95: 299-303
      1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Thymomas and Thymic Carcinomas Version 2.20222022.

        • Lemma GL
        • Lee JW
        • Aisner SC
        • et al.
        Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma.
        J Clin Oncol. 2011; 29: 2060-2065
        • Hirai F
        • Yamanaka T
        • Taguchi K
        • et al.
        A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L.
        Ann Oncol. 2015; 26: 363-368
        • Giaccone G
        • Kim C
        • Thompson J
        • et al.
        Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study.
        Lancet Oncol. 2018; 19: 347-355
        • Cho J
        • Kim HS
        • Ku BM
        • et al.
        Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial.
        J Clin Oncol. 2019; 37: 2162-2170
        • Katsuya Y
        • Horinouchi H
        • Seto T
        • et al.
        Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study.
        Eur J Cancer. 2019; 113: 78-86
        • Girard N
        • Ponce Aix S
        • Cedres S
        • et al.
        LBA66 Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: Results from the EORTC-ETOP NIVOTHYM phase II trial.
        Annals of Oncology. 2021; 32: S1342
        • Giaccone G
        • Kim C.
        Durable Response in Patients With Thymic Carcinoma Treated With Pembrolizumab After Prolonged Follow-Up.
        J Thorac Oncol. 2021; 16: 483-485
        • Meric-Bernstam F
        • Larkin J
        • Tabernero J
        • Bonini C.
        Enhancing anti-tumour efficacy with immunotherapy combinations.
        Lancet. 2021; 397: 1010-1022
        • Smyth MJ
        • Ngiow SF
        • Ribas A
        • Teng MW.
        Combination cancer immunotherapies tailored to the tumour microenvironment.
        Nat Rev Clin Oncol. 2016; 13: 143-158
        • Inoue A
        • Sugawara S
        • Harada M
        • et al.
        Phase II study of Amrubicin combined with carboplatin for thymic carcinoma and invasive thymoma: North Japan Lung Cancer group study 0803.
        J Thorac Oncol. 2014; 9: 1805-1809