Phase 1/2 Study of Mirdametinib + Vinblastine for Newly Diagnosed/Previously Untreated PLGG + Activation of MAPK

Summary

This is a 3-part open-label study (feasibility phase, treatment phase and follow-up phase) of orally administered mirdametinib in combination with intravenous vinblastine chemotherapy in patients with PLGG with activation of MAPK pathway. Feasibility Phase: The maximum tolerated/recommended phase 2 dose (MTD/RP2D) of the mirdametinib plus vinblastine combination will be assessed using a modified Rolling-6 design. Treatment Phase: Patients will receive mirdametinib twice daily (continuously) at a fixed dose (2mg/m2 po BID up to 4 mg BID) for a total of 13 cycles (28 days cycle). Weekly intravenous vinblastine at MTD will be given for a total of 17 cycles. If adverse events occur, two dose reductions are allowed. Follow-up Phase: Following the end of treatment, patients will be scheduled for a follow-up visit every 6 months for 36 months to evaluate PFS, TTP and OS.

Timeline

Start

2026-01-12

Primary completion

2030-04

Completion

2033-04

Publications

• Results Robinson GW, Vinitsky A, Bag AK, et al. LGG-53. RESULTS FROM THE PHASE 1 AND PHASE 1 EXPANSION COHORTS OF SJ901: A PHASE 1/2 TRIAL OF SINGLE-AGENT MIRDAMETINIB (PD-0325901) IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH LOW-GRADE GLIOMA. Neuro Oncol. 2024; 26(Suppl 4):0
• Results Gross AM MC, Warren KE, Widemann BC. Plasma and cerebrospinal fluid pharmacokinetics of selumetinib in non-human primates (NHP). Journal of Clinical Oncology. 2017; 35((15_suppl)):e14070-e14070
• Results Lassaletta A, Scheinemann K, Zelcer SM, Hukin J, Wilson BA, Jabado N, Carret AS, Lafay-Cousin L, Larouche V, Hawkins CE, Pond GR, Poskitt K, Keene D, Johnston DL, Eisenstat DD, Krishnatry R, Mistry M, Arnoldo A, Ramaswamy V, Huang A, Bartels U, Tabori U, Bouffet E. Phase II Weekly Vinblastine for Chemotherapy-Naive Children With Progressive Low-Grade Glioma: A Canadian Pediatric Brain Tumor Consortium Study. J Clin Oncol. 2016 Oct 10;34(29):3537-3543. doi: 10.1200/JCO.2016.68.1585.
• Results Fangusaro J, Onar-Thomas A, Young Poussaint T, Lensing S, Ligon AH, Lindeman N, Banerjee A, Kilburn LB, Lenzen A, Pillay-Smiley N, Pollack IF, Robison NJ, Partap S, Qaddoumi I, Landi D, Jones DTW, Stewart CF, Fouladi M, Dunkel IJ. A phase 2 PBTC study of selumetinib for recurrent/progressive pediatric low-grade glioma: Strata 2, 5, and 6 with long-term outcomes on strata 1, 3, and 4. Neuro Oncol. 2025 Oct 14;27(9):2415-2428. doi: 10.1093/neuonc/noaf065.
• Results Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ, Fouladi M. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019 Jul;20(7):1011-1022. doi: 10.1016/S1470-2045(19)30277-3. Epub 2019 May 28.
• Results Weiss BD, Wolters PL, Plotkin SR, Widemann BC, Tonsgard JH, Blakeley J, Allen JC, Schorry E, Korf B, Robison NJ, Goldman S, Vinks AA, Emoto C, Fukuda T, Robinson CT, Cutter G, Edwards L, Dombi E, Ratner N, Packer R, Fisher MJ. NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas. J Clin Oncol. 2021 Mar 1;39(7):797-806. doi: 10.1200/JCO.20.02220. Epub 2021 Jan 28.
• Results Jones DT, Gronych J, Lichter P, Witt O, Pfister SM. MAPK pathway activation in pilocytic astrocytoma. Cell Mol Life Sci. 2012 Jun;69(11):1799-811. doi: 10.1007/s00018-011-0898-9. Epub 2011 Dec 13.
• Results Packer RJ, Lange B, Ater J, Nicholson HS, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN, et al. Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol. 1993 May;11(5):850-6. doi: 10.1200/JCO.1993.11.5.850.
• Results Sievert AJ, Fisher MJ. Pediatric low-grade gliomas. J Child Neurol. 2009 Nov;24(11):1397-408. doi: 10.1177/0883073809342005.
• Results Fangusaro J, Witt O, Hernaiz Driever P, Bag AK, de Blank P, Kadom N, Kilburn L, Lober RM, Robison NJ, Fisher MJ, Packer RJ, Young Poussaint T, Papusha L, Avula S, Brandes AA, Bouffet E, Bowers D, Artemov A, Chintagumpala M, Zurakowski D, van den Bent M, Bison B, Yeom KW, Taal W, Warren KE. Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol. 2020 Jun;21(6):e305-e316. doi: 10.1016/S1470-2045(20)30064-4.

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