First-line CBDCA/PTX/LEN/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas (Artemis)

Summary

A phase II, investigator-initiated, non-randomized, open-label, single-arm, multicenter study to evaluate the efficacy and safety of Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab combination for previously untreated advanced or recurrent thymic carcinomas

Timeline

Start

2023-09-04

Primary completion

2025-12-31

Completion

2028-06-30

Publications

• Results Gandhi L, Garassino MC. Pembrolizumab plus Chemotherapy in Lung Cancer. N Engl J Med. 2018 Sep 13;379(11):e18. doi: 10.1056/NEJMc1808567. No abstract available.
• Results Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003 Jun;9(6):669-76. doi: 10.1038/nm0603-669.
• Results Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008 Aug;8(8):579-91. doi: 10.1038/nrc2403. Epub 2008 Jul 3.
• Results Cross MJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci. 2001 Apr;22(4):201-7. doi: 10.1016/s0165-6147(00)01676-x.
• Results Lieu C, Heymach J, Overman M, Tran H, Kopetz S. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clin Cancer Res. 2011 Oct 1;17(19):6130-9. doi: 10.1158/1078-0432.CCR-11-0659. Epub 2011 Sep 27.
• Results Phay JE, Shah MH. Targeting RET receptor tyrosine kinase activation in cancer. Clin Cancer Res. 2010 Dec 15;16(24):5936-41. doi: 10.1158/1078-0432.CCR-09-0786. Epub 2010 Oct 7.
• Results Katsuya Y, Horinouchi H, Asao T, Kitahara S, Goto Y, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Watanabe S, Tsuta K, Ohe Y. Expression of programmed death 1 (PD-1) and its ligand (PD-L1) in thymic epithelial tumors: Impact on treatment efficacy and alteration in expression after chemotherapy. Lung Cancer. 2016 Sep;99:4-10. doi: 10.1016/j.lungcan.2016.05.007. Epub 2016 May 12.
• Results Cho J, Kim HS, Ku BM, Choi YL, Cristescu R, Han J, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial. J Clin Oncol. 2019 Aug 20;37(24):2162-2170. doi: 10.1200/JCO.2017.77.3184. Epub 2018 Jun 15.
• Results Giaccone G, Kim C, Thompson J, McGuire C, Kallakury B, Chahine JJ, Manning M, Mogg R, Blumenschein WM, Tan MT, Subramaniam DS, Liu SV, Kaplan IM, McCutcheon JN. Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet Oncol. 2018 Mar;19(3):347-355. doi: 10.1016/S1470-2045(18)30062-7. Epub 2018 Jan 26.
• Results Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol. 2015 Sep;10(9):1240-1242. doi: 10.1097/JTO.0000000000000663. No abstract available.
• Results Detterbeck FC, Huang J. Overview. J Thorac Oncol. 2011 Jul;6(7 Suppl 3):S1689-90. doi: 10.1097/JTO.0b013e31821e7afe. No abstract available.
• Results Girard N, Lal R, Wakelee H, Riely GJ, Loehrer PJ. Chemotherapy definitions and policies for thymic malignancies. J Thorac Oncol. 2011 Jul;6(7 Suppl 3):S1749-55. doi: 10.1097/JTO.0b013e31821ea5f7. No abstract available.
• Results Detterbeck FC, Stratton K, Giroux D, Asamura H, Crowley J, Falkson C, Filosso PL, Frazier AA, Giaccone G, Huang J, Kim J, Kondo K, Lucchi M, Marino M, Marom EM, Nicholson AG, Okumura M, Ruffini E, Van Schil P; Staging and Prognostic Factors Committee; Members of the Advisory Boards; Participating Institutions of the Thymic Domain. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol. 2014 Sep;9(9 Suppl 2):S65-72. doi: 10.1097/JTO.0000000000000290.
• Results Lemma GL, Lee JW, Aisner SC, Langer CJ, Tester WJ, Johnson DH, Loehrer PJ Sr. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol. 2011 May 20;29(15):2060-5. doi: 10.1200/JCO.2010.32.9607. Epub 2011 Apr 18.
• Results Hirai F, Yamanaka T, Taguchi K, Daga H, Ono A, Tanaka K, Kogure Y, Shimizu J, Kimura T, Fukuoka J, Iwamoto Y, Sasaki H, Takeda K, Seto T, Ichinose Y, Nakagawa K, Nakanishi Y; West Japan Oncology Group. A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L. Ann Oncol. 2015 Feb;26(2):363-8. doi: 10.1093/annonc/mdu541. Epub 2014 Nov 17.
• Results Katsuya Y, Fujita Y, Horinouchi H, Ohe Y, Watanabe S, Tsuta K. Immunohistochemical status of PD-L1 in thymoma and thymic carcinoma. Lung Cancer. 2015 May;88(2):154-9. doi: 10.1016/j.lungcan.2015.03.003. Epub 2015 Mar 10.
• Results Katsuya Y, Horinouchi H, Seto T, Umemura S, Hosomi Y, Satouchi M, Nishio M, Kozuki T, Hida T, Sukigara T, Nakamura K, Kuchiba A, Ohe Y. Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study. Eur J Cancer. 2019 May;113:78-86. doi: 10.1016/j.ejca.2019.03.012. Epub 2019 Apr 13.
• Results Sato J, Satouchi M, Itoh S, Okuma Y, Niho S, Mizugaki H, Murakami H, Fujisaka Y, Kozuki T, Nakamura K, Nagasaka Y, Kawasaki M, Yamada T, Machida R, Kuchiba A, Ohe Y, Yamamoto N. Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial. Lancet Oncol. 2020 Jun;21(6):843-850. doi: 10.1016/S1470-2045(20)30162-5.
• Results Girard N, Ruffini E, Marx A, Faivre-Finn C, Peters S; ESMO Guidelines Committee. Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep;26 Suppl 5:v40-55. doi: 10.1093/annonc/mdv277. No abstract available.
• Results Yokoi K, Matsuguma H, Nakahara R, Kondo T, Kamiyama Y, Mori K, Miyazawa N. Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol. 2007 Jan;2(1):73-8. doi: 10.1097/JTO.0b013e31802bafc8.
• Results Nishio M, Horai T, Horiike A, Nokihara H, Yamamoto N, Takahashi T, Murakami H, Yamamoto N, Koizumi F, Nishio K, Yusa W, Koyama N, Tamura T. Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients with non-small-cell lung cancer. Br J Cancer. 2013 Aug 6;109(3):538-44. doi: 10.1038/bjc.2013.374. Epub 2013 Jul 16.
• Results Padda SK, Riess JW, Schwartz EJ, Tian L, Kohrt HE, Neal JW, West RB, Wakelee HA. Diffuse high intensity PD-L1 staining in thymic epithelial tumors. J Thorac Oncol. 2015 Mar;10(3):500-8. doi: 10.1097/JTO.0000000000000429.
• Results Giaccone G, Kim C. Durable Response in Patients With Thymic Carcinoma Treated With Pembrolizumab After Prolonged Follow-Up. J Thorac Oncol. 2021 Mar;16(3):483-485. doi: 10.1016/j.jtho.2020.11.003. Epub 2020 Nov 25.
• Results Havel JJ. MEK Inhibitors in Lung Cancer-You Can Teach an Old Drug New Tricks. Cancer Res. 2019 Nov 15;79(22):5699-5701. doi: 10.1158/0008-5472.CAN-19-2590.
• Results Radovich M, Pickering CR, Felau I, Ha G, Zhang H, Jo H, Hoadley KA, Anur P, Zhang J, McLellan M, Bowlby R, Matthew T, Danilova L, Hegde AM, Kim J, Leiserson MDM, Sethi G, Lu C, Ryan M, Su X, Cherniack AD, Robertson G, Akbani R, Spellman P, Weinstein JN, Hayes DN, Raphael B, Lichtenberg T, Leraas K, Zenklusen JC; Cancer Genome Atlas Network; Fujimoto J, Scapulatempo-Neto C, Moreira AL, Hwang D, Huang J, Marino M, Korst R, Giaccone G, Gokmen-Polar Y, Badve S, Rajan A, Strobel P, Girard N, Tsao MS, Marx A, Tsao AS, Loehrer PJ. The Integrated Genomic Landscape of Thymic Epithelial Tumors. Cancer Cell. 2018 Feb 12;33(2):244-258.e10. doi: 10.1016/j.ccell.2018.01.003.
• Results Petrini I, Meltzer PS, Kim IK, Lucchi M, Park KS, Fontanini G, Gao J, Zucali PA, Calabrese F, Favaretto A, Rea F, Rodriguez-Canales J, Walker RL, Pineda M, Zhu YJ, Lau C, Killian KJ, Bilke S, Voeller D, Dakshanamurthy S, Wang Y, Giaccone G. A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nat Genet. 2014 Aug;46(8):844-9. doi: 10.1038/ng.3016. Epub 2014 Jun 29.
• Results Hirai F, Seto T, Inamasu E, Toyokawa G, Yoshida T, Nosaki K, Takenaka T, Yamaguchi M, Takenoyama M, Ichinose Y. Results of S-1-based chemotherapy for platinum (and antrathycline)-refractory advanced thymic carcinoma. Anticancer Res. 2014 Oct;34(10):5743-7.
• Results Shepherd A, Riely G, Detterbeck F, Simone CB 2nd, Ahmad U, Huang J, Korst R, Rajan A, Rimner A. Thymic Carcinoma Management Patterns among International Thymic Malignancy Interest Group (ITMIG) Physicians with Consensus from the Thymic Carcinoma Working Group. J Thorac Oncol. 2017 Apr;12(4):745-751. doi: 10.1016/j.jtho.2016.11.2219. Epub 2016 Nov 19.
• Okuma Y, Nomura S, Sakakibara-Konishi J, Tsukita Y, Murakami S, Hosomi Y, Tambo Y, Kogure Y, Yoshioka H, Tamiya M, Ninomiya K, Iwama E. Artemis: A Multicenter, Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of First-Line Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas. Clin Lung Cancer. 2024 Jun;25(4):389-394. doi: 10.1016/j.cllc.2024.02.002. Epub 2024 Feb 8.

Drugs

Indications