Company: ERAS
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0000950170-25-042682
Chunk: 23

Company: Erasca, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 23
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 An MTD was not identified for the QD schedule while the MTD/recommended dose for expansion (RDE) for the BID schedule was determined to be 600 mg twice a day (BID). The monotherapy dose expansion portion of the trial was not opened in order to focus on combination development. During naporafenib monotherapy dose escalation, five patients experienced seven dose-limiting toxicities: decreased platelet count (1200 mg QD); neuralgia, maculopapular rash, pruritus (600 mg BID); increased blood bilirubin, hyponatremia, peripheral sensory neuropathy (800 mg BID). For the single-agent cohort, treatment-related adverse events (TRAEs) of any grade were reported in 79 (90.8%) patients. The most frequent (occurring in ≥20% of patients) were dermatitis acneiform (maculopapular pustular eruptions) (24.1%, no Grade 3/4 events), rash (24.1%, Grade 3/4: 1.1%), and fatigue (20.7%, Grade 3/4: 2.3%). 

Naporafenib plus trametinib. Three trials have evaluated the combination of naporafenib plus trametinib: the dose finding Phase 1b CLXH254X2102 trial, the Phase 2 CLXH254C12201 trial, and the Phase 1b SEACRAFT-1 trial.

The CLXH254X2102 trial enrolled patients who had advanced or metastatic KRAS or BRAF mutant NSCLC or NRASm melanoma with progression following SOC treatment. A total of 115 patients were treated with naporafenib plus trametinib in combination in 5 dose cohorts. Four cohorts received naporafenib and trametinib (doses are listed as naporafenib mg BID/trametinib mg QD): 200/0.5 (6 patients), 200/1 (54 patients), 400/0.5 (44 patients), 400/1 (5 patients), and a fifth cohort was administered 400 mg naporafenib BID continuously and trametinib 1 mg QD following a 2 weeks on/2 weeks off schedule (6 patients). Thirty-six patients in total were enrolled in dose escalation while 30 were enrolled in the NRASm melanoma expansion