Phase II Study of Ulixertinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Alterations: APEC1621J of the National Cancer Institute-Children’s Oncology Group Pediatric MATCH Trial

Vo KT, Sabnis AJ, Williams PM, Roy-Chowdhuri S, Patton DR, Coffey B, Reid JM, Piao J, Saguilig L, Alonzo TA, Berg SL, Jaju A, Fox E, Weigel BJ, Hawkins DS, Mooney MM, Takebe N, Tricoli JV, Janeway KA, Seibel NL, Parsons DW. Phase II Study of Ulixertinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Alterations: APEC1621J of the National Cancer Institute-Children’s Oncology Group Pediatric MATCH Trial. JCO Precis Oncol. 2024 Jun;8:e2400103. doi: 10.1200/PO.24.00103. PubMed PMID: 38935895; NIHMSID:NIHMS2024995.

The NCI-COG Pediatric MATCH trial assigns patients age 1 to 21 years with refractory malignancies to phase 2 treatment arms of molecularly-targeted therapies based on genetic alterations detected in their tumor. Patients with activating alterations in the MAPK pathway were treated with ulixertinib, an ERK1/2 inhibitor. As there were no prior pediatric data, ulixertinib was initially tested in a dose escalation cohort to establish the recommended phase 2 dose (RP2D) before proceeding to the phase 2 cohort. Ulixertinib was administered at 260 mg/m2/dose PO BID (dose level 1, DL1, n=15) or 350 mg/m2/dose PO BID (DL2, n=5). The primary endpoint was objective response rate; secondary endpoints included safety/tolerability and progression-free survival (PFS).