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

Company: Erasca, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 25
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 1.9%), blood creatinine phosphokinase increased (20.8%, Grade 3/4:1.9%), and fatigue (20.8%, Grade 3/4: 1.9%).

The SEACRAFT-1 trial enrolled patients with RAS Q61X mutations across multiple tumor types including melanoma, lung, thyroid, and GI malignancies. As presented at the 2024 Triple Meeting, the combination of naporafenib plus trametinib, evaluated at the 200/1 dose (52 patients), was generally well tolerated with primarily Grade 1 and 2 TRAEs observed. In addition, the frequency of Grade 3 or higher TRAEs was approximately 5% or less across the various categories of events.

In particular, the incidence and severity of skin toxicities improved dramatically in SEACRAFT-1 relative to the prior Phase 1 and 2 trials. We believe these improved AE outcomes were likely due to the implementation of mandatory primary rash prophylaxis as part of our SEACRAFT-1 and -2 trials. More specifically, in SEACRAFT-1, the rate of Grade 3 or higher dermatological toxicities decreased from about 37% in the historical Phase 1 and 2 trials to around 12% in SEACRAFT-1.

Furthermore, although differences exist between trial designs, sites, and patient characteristics, which limit our ability to compare across clinical trial programs, the rate of drug discontinuations due to adverse events markedly decreased from about 19 to 20% in the Phase 1 and 2 trials conducted by Novartis to less than 10% in our SEACRAFT-1 trial. The relative dose intensity (RDI), which is a measure of how much drug a patient receives relative to the trial’s intent, also showed a marked improvement. More specifically, the median RDI of naporafenib increased from 66% and 57%, respectively, for the Novartis Phase 1 and 2 trials to nearly 99% in SEACRAFT-1. Additionally, the median RDI for trametinib increased to nearly 100% in SEACRAFT-1 compared to 59-62% in the Novartis Phase 1 and 2 trials.

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Summary. Naporafenib administered as monotherapy was generally well tolerated when administered using either a QD or BID schedule. Naporafenib was also generally well tolerated when administered with multiple other therapies