Gomekli (mirdametinib) confirmed medical exercise with acceptable security in youngsters, adolescents and younger adults with recurrent or progressive low-grade glioma (pLGG) with biopsy-proven MAPK pathway activation who had not been handled with a previous MEK inhibitor, in keeping with findings from the section 1/2 SJ901 trial, introduced on the 2025 SNO Annual Assembly.
At an information cutoff date of September 23, 2025, the general response charge (ORR) per Response Evaluation in Pediatric Low-Grade Glioma radiological response standards was 87%, together with minor response or higher (87%), partial response (PR) or higher (55%), main response or higher (26%), and full response (6%). The median time to minor response or higher was 6 months, and the median time to PR or higher was 10.7 months.
Total, the efficacy of Gomekli was seen in 36% of sufferers who obtained the agent at 2 milligram per sq. meter (mg/m2) or 2.5 mg/m2 and 46% of those that obtained it at 3 mg/m2. Subsequently, the beneficial section 2 dose (RP2D) was recognized to be 3 mg/m2 twice each day given orally and for steady dosing primarily based on the discovering that just one affected person out of 12 who obtained the agent at this dose degree had a dose-limiting toxicity (DLT; grade 3 thrombocytopenia).
“We’re very excited concerning the preliminary efficacy,” lead examine creator and presenter Dr. Anna Vinitsky, stated in an interview with OncLive® in the course of the assembly. Vinitsky is an affiliate member of St. Jude College at St. Jude Kids’s Analysis Hospital in Memphis, Tennessee.
Remedy-related adversarial results (TRAEs) that led to dose reductions (34%) included grade 3 (extreme) weight acquire (8 sufferers), grade 4 (life-threatening) elevated creatine phosphokinase (CPK) ranges (2 sufferers), grade 3 elevated alanine aminotransferase (ALT) ranges (1 affected person), and decreased platelet counts (1 affected person). TRAEs that led to remedy discontinuations (6%) included insupportable grade 2 rash (1 affected person) and grade 4 elevated CPK ranges (1 affected person). AEs of particular curiosity included asymptomatic grade 2 decreased left ventricular ejection fraction to lower than 50% (3 sufferers); every had spontaneous decision. Notably, investigators didn’t report retinal toxicities of any grade.
“We’re fairly thrilled that sufferers are tolerating the drug properly,” Dr. Giles W. Robinson, added within the interview. “They’ve a number of the extra customary AEs we see with MEK inhibitors, that are rashes, paronychia, or ingrown toenails. However these are comparatively minor [AEs] that the sufferers be taught to handle, or dad and mom be taught to handle for the sufferers.”
Robinson is a member of St. Jude College, director of the Division of Neuro-Oncology, co-leader of Most cancers Middle Neurobiology and Mind Tumor Program in Memphis.
What was the rationale for the SJ901 trial of Gomekli in pLGG?
Though MEK inhibitors have proven promise as remedy for pediatric low-grade glioma, they typically have restricted penetrance to the blood-brain barrier and are sometimes not obtainable in oral formulations, in keeping with the examine authors. Gomekli, nevertheless, is an oral, selective, small-molecule MEK inhibitor that may penetrate the blood-brain barrier and will be administered in a dispersible pill formulation that’s extra amenable for the wants of younger youngsters and sufferers for whom swallowing drugs is a problem. Gomekli was FDA accepted in February 2025 for the remedy of grownup and pediatric sufferers a minimum of two years of age with neurofibromatosis kind 1 (NF1) who’ve symptomatic plexiform neurofibromas (PNs) that aren’t amenable to finish resection.
Based mostly on Gomekli’s mechanism of motion, oral formulation, and efficacy in sufferers with NF1 PNs, investigators launched the SJ901 trial to research the agent in sufferers with pLGG.
What was the design of the SJ901 trial?
This multi-arm trial enrolled sufferers with pLGG a minimum of 2 years of age however youthful than 25 years of age. The section 1 portion of the trial enrolled these with recurrent or progressive pLGG with biopsy-proven MAPK pathway activation (besides in BRAF V600) who had no prior publicity to a MEK inhibitor. MAPK pathway activation was defied as BRAF fusions or rearrangements; FGFR1/2/3 aberrations; NF1, NF2, PTPN11, SOS1, RAF1 and RAS mutations; and MYB or MYBL1 fusions or rearrangements, all recognized by immunohistochemistry, fluorescence in situ hybridization, and/or DNA/RNA sequencing.
Sufferers obtained Gomekli at 1 of three escalating dose ranges (2 mg/m2, 2.5 mg/m2, or 3 mg/m2) twice each day on a steady schedule over 24 months. An enlargement cohort was designed to seek out the best tolerated dose degree, which might develop into the RP2D, in 12 sufferers. As soon as the RP2D was recognized, an extra 12 sufferers have been handled at this degree to find out the efficacy of the agent throughout 24 complete sufferers. The RP2D was outlined because the dose that was related to 3 or fewer DLTs in 12 sufferers; DLTs have been outlined as any toxicities that restricted the administration of a given Gomekli dose inside the first cycle of remedy.
The first aims of SJ901 have been to discover the security, tolerability, and preliminary efficacy of steady Gomekli administration in addition to to determine the RP2D of the agent.
What further efficacy findings have been reported from the SJ901 trial at SNO 2025?
Between June 2021 and September 2025, 35 complete sufferers have been enrolled to the section 1, section 1 enlargement, and section 2 cohort 2 parts of the trial. Within the total inhabitants, the median age at prognosis was 8.3 years, and most sufferers have been male (54%) and White (77%). Main diagnoses included pilocytic astrocytoma (83%), diffuse glioma (6%), diffuse leptomeningeal glioneuronal tumor (3%), glioneuronal tumor (3%), and LGG not in any other case specified (6%). MAPK gene abnormalities have been seen in BRAF (65%), FGFR1 (17%), MYB (3%), NF1 (9%), and RAF1 (6%).
At a median follow-up of 23.9 months, 83% of sufferers had accomplished or remained on remedy. In complete, 17% of sufferers had discontinued remedy on account of development (4 sufferers; FGFR aberration, 2 sufferers; MYB fusion or rearrangement, 1 affected person; BRAF fusion or rearrangement, 1 affected person) and toxicity (2 sufferers; rash and elevated CPK ranges). Moreover, 9 sufferers progressed both on remedy (5 sufferers) or after finishing remedy (4 sufferers).
“Sufferers [had] greater than 50% reductions within the measurement of their tumor, which a few of these tumors are fairly giant and are inflicting plenty of debilitating deficits in our affected person inhabitants,” Robinson added. “After we see that [reduction], we additionally see that these sufferers are extremely thriving.”
What further security findings have been reported with Gomekli in pLGG?
In complete, the commonest TRAEs included elevated CPK ranges (35 sufferers), elevated aspartate aminotransferase ranges (32 sufferers), dry pores and skin (19 sufferers), acneiform rash (18 sufferers), anemia (16 sufferers), weight acquire (16 sufferers), paronychia (15 sufferers), hair shade adjustments (14 sufferers), elevated ALT ranges (12 sufferers), elevated alkaline phosphatase ranges (12 sufferers), decreased neutrophil counts (11 sufferers), maculopapular rash (11 sufferers), eczema (8 sufferers), hypoalbuminemia (8 sufferers), nausea (8 sufferers), diarrhea (7 sufferers), hypomagnesemia (7 sufferers), proteinuria (7 sufferers), decreased platelet counts (6 sufferers), pores and skin and subcutaneous tissue issues or different TRAEs (6 sufferers), fatigue (5 sufferers), and hypernatremia (5 sufferers).
What are the following steps for evaluating Gomekli in sufferers with pLGG?
Continued outcomes can be shared from the trial as the information from this affected person cohort mature, in keeping with the examine authors. Cohorts 1 and three of the section 2 portion of the trial are enrolling newly recognized sufferers and those that have been beforehand handled with MEK inhibition, respectively.
“We’d like to see this drug develop into an ordinary remedy in LGG,” Robinson concluded. “That’s the course we’re heading [in]. There must be extra research in taking a look at how does this drug fare with different MEK inhibitors, and the way does it fare as compared with what we take into account customary of care? However to be trustworthy, [from] treating sufferers and seeing sufferers within the clinic thriving on this remedy, it looks like they’re doing significantly better than what we’ve seen with customary chemotherapies. We’re inspired that this can develop into one of many therapies of the longer term for LGG.”
References
- “Efficacy and tolerability of mirdametinib (PD-0325901) in youngsters, adolescents, and younger adults with recurrent/progressive low-grade glioma: replace from the SJ901 (NCT04923126) section 1/2 medical trial,” by Dr. Vinitsky A, Bag AK, Chiang J, et al. Introduced at: 2025 SNO Annual Assembly; November 19-23, 2025; Honolulu, Hawaii. Summary CTP-08.
- “FDA approves mirdametinib for grownup and pediatric sufferers with neurofibromatosis kind 1 who’ve symptomatic plexiform neurofibromas not amenable to finish resection.” FDA. February 11, 2025. Accessed November 21, 2025.
https://www.fda.gov/medicine/resources-information-approved-drugs/fda-approves-Gomekli-adult-and-pediatric-patients-neurofibromatosis-type-1-who-have-symptomatic
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