Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib in Subjects With BRAF V600E- Mutated Rare Cancers

Summary

This was a Phase II, open-label, non-randomized, multi-center study of oral dabrafenib in combination with oral trametinib in subjects with rare cancers harboring the BRAF V600E mutation including anaplastic thyroid cancer (ATC), biliary tract cancer (BTC), gastrointestinal stromal tumor (GIST), low grade (WHO G1/G2) glioma (LGG), high grade (WHO G3/G4) glioma (HGG), non-seminomatous germ cell tumors (NSGCT) / non-germinomatous germ cell tumors (NGGCT), adenocarcinoma of the small intestine (ASI), hairy cell leukemia (HCL) and multiple myeloma (MM).

Timeline

Start

2014-03-12

Primary completion

2021-12-10

Completion

2021-12-10

Publications

• Subbiah V, Burris HA 3rd, Kurzrock R. Revolutionizing cancer drug development: Harnessing the potential of basket trials. Cancer. 2024 Jan;130(2):186-200. doi: 10.1002/cncr.35085. Epub 2023 Nov 7.
• Hicks HM, Pozdeyev N, Sams SB, Pugazhenthi U, Bales ES, Hofmann MC, McKenna LR, Schweppe RE. Fibronectin Contributes to a BRAF Inhibitor-driven Invasive Phenotype in Thyroid Cancer through EGR1, Which Can Be Blocked by Inhibition of ERK1/2. Mol Cancer Res. 2023 Sep 1;21(9):867-880. doi: 10.1158/1541-7786.MCR-22-1031.
• Subbiah V, Kreitman RJ, Wainberg ZA, Gazzah A, Lassen U, Stein A, Wen PY, Dietrich S, de Jonge MJA, Blay JY, Italiano A, Yonemori K, Cho DC, de Vos FYFL, Moreau P, Fernandez EE, Schellens JHM, Zielinski CC, Redhu S, Boran A, Passos VQ, Ilankumaran P, Bang YJ. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. Nat Med. 2023 May;29(5):1103-1112. doi: 10.1038/s41591-023-02321-8. Epub 2023 Apr 14.
• Kreitman RJ, Moreau P, Ravandi F, Hutchings M, Gazzah A, Michallet AS, Wainberg ZA, Stein A, Dietrich S, de Jonge MJA, Willenbacher W, De Greve J, Arons E, Ilankumaran P, Burgess P, Gasal E, Subbiah V. Dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia. Blood. 2023 Mar 2;141(9):996-1006. doi: 10.1182/blood.2021013658.
• Wen PY, Stein A, van den Bent M, De Greve J, Wick A, de Vos FYFL, von Bubnoff N, van Linde ME, Lai A, Prager GW, Campone M, Fasolo A, Lopez-Martin JA, Kim TM, Mason WP, Hofheinz RD, Blay JY, Cho DC, Gazzah A, Pouessel D, Yachnin J, Boran A, Burgess P, Ilankumaran P, Gasal E, Subbiah V. Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol. 2022 Jan;23(1):53-64. doi: 10.1016/S1470-2045(21)00578-7. Epub 2021 Nov 24.
• Subbiah V, Lassen U, Elez E, Italiano A, Curigliano G, Javle M, de Braud F, Prager GW, Greil R, Stein A, Fasolo A, Schellens JHM, Wen PY, Viele K, Boran AD, Gasal E, Burgess P, Ilankumaran P, Wainberg ZA. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020 Sep;21(9):1234-1243. doi: 10.1016/S1470-2045(20)30321-1. Epub 2020 Aug 17.
• Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, Wen PY, Zielinski C, Cabanillas ME, Urbanowitz G, Mookerjee B, Wang D, Rangwala F, Keam B. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol. 2018 Jan 1;36(1):7-13. doi: 10.1200/JCO.2017.73.6785. Epub 2017 Oct 26.
• Lee EQ, Ruland S, LeBoeuf NR, Wen PY, Santagata S. Successful Treatment of a Progressive BRAF V600E-Mutated Anaplastic Pleomorphic Xanthoastrocytoma With Vemurafenib Monotherapy. J Clin Oncol. 2016 Apr 1;34(10):e87-9. doi: 10.1200/JCO.2013.51.1766. Epub 2014 Aug 4. No abstract available.

Drugs

Indications