(P 424) AN OPEN-LABEL PHASE 1/2 STUDY OF DCC-3009 MONOTHERAPY IN PATIENTS (PTS) WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR (GIST)

Objective: KIT and platelet-derived growth factor receptor α (PDGFRA) mutations remain key oncogenic drivers in most pts with advanced GIST, and acquired secondary drug-resistant mutations contribute to the heterogeneity of the disease. The diversity of these mutations allows escape from standard-of-care tyrosine kinase inhibitor (TKI) therapy, creating an unmet need for novel therapies that inhibit all clinically relevant mutations. DCC-3009 is an investigational, highly potent, and selective switch-control KIT and PDGFRA inhibitor designed to act against known clinically relevant primary and secondary GIST-driving mutations while limiting off-target effects. In preclinical studies, DCC-3009 showed strong antitumor effects in xenograft models driven by resistant KIT mutations, optimized properties for oral administration, and low risk of cytochrome P450 inhibition. Here, we describe an ongoing study of DCC-3009.

Methods: This multicohort, open-label, phase 1/2 trial is evaluating the safety, tolerability, and efficacy of DCC-3009 in pts with advanced GIST (NCT06630234) using a modular approach. Each trial module is defined by the therapy (DCC-3009 alone or with other anticancer agents) and divided into dose escalation and dose expansion. For inclusion in the monotherapy dose escalation, adult pts must have histologically or cytologically confirmed advanced GIST with documented KIT or PDGFRA mutation, progression on or intolerance to ≥1 approved TKI regimen in the advanced setting (imatinib if KIT-mutant), ≥1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST v1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1 at screening. Exclusion criteria include receiving systemic anticancer therapy within 14 days or < 5 half-lives, radiotherapy within 14 days prior to first dose of study drug, prior or concurrent malignancy requiring or expected to need treatment, known allergy or hypersensitivity to the study drug components or excipients, and impaired oral absorption or malabsorption syndrome. Pts enrolled in monotherapy dose escalation will receive oral DCC-3009 in 28-day cycles. The primary outcome measures include safety assessments. Secondary outcome measures include objective response rate, duration of response, progression-free survival by mRECIST v1.1, overall survival, and pharmacokinetics. Abstract originally presented at ASCO 2025 in Chicago, IL, USA.

Results: N/A

Conclusion: N/A