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Lung Cancer Treatments and Mutations / Colorectal Cancer Treatments and Studies · Journal article
Clinical Cancer Research · August 11, 2026
Early or partial results. Treat as a signal, not a conclusion.
Ulixertinib, an ERK1/2 inhibitor, demonstrated no objective responses and minimal clinical activity in a small cohort of 34 heavily pretreated patients with BRAF non-V600 mutations or BRAF fusions. Median progression-free survival was 1.7 months and median overall survival 3.5 months, with stable disease achieved in 27% of centrally confirmed cases. This negative result does not support further development of single-agent ulixertinib in this population without biomarker refinement or combination strategies.
Single-arm, open-label Phase 2 trial. Patients aged ≥18 years (median 66.5) with tumors harboring BRAF non-V600 mutations or BRAF fusions; enrolled from NCI-MATCH trial; 88% white, 50% female, 74% ECOG PS 1; heavily pretreated with median 4 prior therapies.. Intervention: Ulixertinib (ERK1/2 inhibitor), 600 mg orally twice daily, continuous dosing in 28-day cycles. n = 34. NCI-MATCH ECOG-ACRIN trial (EAY131); specific sites not detailed in abstract..
ORR = 0% (0 complete or partial responses in 34 eligible patients) Stable disease achieved in 7/26 centrally confirmed cases (27%) Median PFS 1.7 months (90% CI: 1.1, 2.2)
Grade 3 toxicities in 20/35 patients (57%); 1 grade 4 toxicity (3%)
This negative Phase 2 result does not support use of ulixertinib monotherapy in this patient population. Clinicians should not pursue this agent as a single agent for BRAF non-V600 or fusion-positive tumors without additional data on combination approaches or patient selection biomarkers. The poor outcomes in a heavily pretreated population limit extrapolation to treatment-naïve or earlier-line settings.
Single-arm Phase 2 study in a small, heavily pretreated population showing no objective responses; negative result limits strength but rigorous conduct and clear null finding warrant reporting.
As stated by the source record.
Quoted from the source exactly as published.
This negative Phase 2 result does not support use of ulixertinib monotherapy in this patient population. Clinicians should not pursue this agent as a single agent for BRAF non-V600 or fusion-positive tumors without additional data on combination approaches or patient selection biomarkers. The poor outcomes in a heavily pretreated population limit extrapolation to treatment-naïve or earlier-line settings.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
PURPOSE: Mutations in BRAF at codons other than V600 (non-V600) and BRAF fusions confer dependence on RAF-MEK-ERK pathway. Subprotocol Z1L (EAY131-Z1L) investigated the clinical activity of ulixertinib (ERK1/2 inhibitor) in patients with tumors harboring these alterations. PATIENTS AND METHODS: In this single-arm study, patients with BRAF non-V600 mutation or BRAF fusion were given ulixertinib orally, at a dose of 600 mg twice daily, continuously for each 28-day cycle until progression or intolerability. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). RESULTS: Among 34 eligible patients, median age was 66.5; 50% were female, 88% were white, 9% black, 3% Asian. ECOG PS 1 in 74% of patients. Median number of prior therapies was 4. Tumor types included multiple gastrointestinal malignancies (n = 16), lung cancer, melanoma (n = 3 each), among others. No patients achieved CR or PR, resulting in ORR = 0%. Stable disease was the best response in 7/26 centrally confirmed cases. Median PFS was 1.7 months (90% CI: 1.1, 2.2), 6-month PFS rate was 5% (90% CI: 0.6%, 17.7%), and median OS was 3.5 months (90% CI: 1.9, 5.4). Twenty patients (57%) had grade 3 toxicities, and one patient (3%) had grade 4 toxicity as their worst toxicity; there were no grade 5 toxicities. CONCLUSION: Ulixertinib had no demonstrable evidence of clinical activity in this small, heavily pretreated population of patients with tumors harboring BRAF fusions, or with non-V600E, non-V600K BRAF mutations.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.