Company: ERAS
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0000950170-25-042682
Chunk: 24

Company: Erasca, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 24
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 cohorts. During dose escalation, six patients reported 6 DLTs: dermatitis acneiform (one patient each in the 200/1 and 400/0.5 cohorts), maculopapular rash (one patient each in the 200/1 and 400/1 cohorts), increased lipase (one patient in the 200/1 cohort), and Stevens-Johnson syndrome (one patient in the 400/1 cohort). Two RDEs were identified: naporafenib 200 mg BID plus trametinib 1 mg QD and naporafenib 400 mg BID plus trametinib 0.5 mg QD. For the dose expansion portion of the trial, TRAEs of any grade were reported in 100% of patients. The most frequent (occurring in ≥20% of patients enrolled in dose expansion) TRAEs were rash (80.0%, Grade 3/4: 33.3%), nausea (30.0%, no Grade 3/4 events), diarrhea (30.0%, no Grade 3/4 events), blood creatinine phosphokinase increased (30.0%, Grade 

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3/4: 13.3%), constipation (23.0%, no Grade 3/4 events), stomatitis (20.0%, Grade 3/4: 3.3%) and vomiting (20.0%, no Grade 3/4 events).

The CLXH254C12201 trial enrolled patients with NRASm or BRAFm melanoma who have received prior systemic therapy for unresectable or metastatic melanoma with an anti-PD-1/L1-based regimen and were restricted to a maximum of two prior lines of systemic immune checkpoint inhibitor (ICI)-containing immunotherapy for unresectable or metastatic melanoma. The combination of naporafenib plus trametinib was evaluated at the RDEs of 200/1 (30 patients) and 400/0.5 (22 patients) where both naporafenib plus trametinib were administered continuously BID and QD, respectively. The most frequent (occurring in ≥20% of patients) TRAEs were rash (39.6%, Grade 3/4: 9.4%), dermatitis acneiform (34.0%, Grade 3/4: 7.5%), pruritis (26.4%, Grade 3/4: