1170P Updated efficacy and safety data from the phase I/II ARROW study of pralsetinib in patients (pts) with advanced RET fusion+ non-small cell lung cancer (NSCLC)

Pralsetinib is FDA/EMA approved for the treatment of advanced RET fusion+ NSCLC based on the global multicohort, open-label, Phase 1/2 ARROW study. Prior results from ARROW show that pralsetinib has promising anti-tumour activity with a manageable safety profile in advanced RET fusion+ NSCLC (Gainor JF, et al. Lancet Oncol 2021). We present updated data from the RET fusion+ NSCLC cohort after an additional 16 months of follow-up since the previous analysis. Phase 1 established the recommended Phase 2 dose of pralsetinib (400mg once daily). In the RET fusion+ NSCLC cohort, pts ≥18 years with ECOG PS 0–2 (limited to 0–1 after a protocol amendment) and locally documented RET fusions received pralsetinib until disease progression, intolerance or withdrawal. Primary endpoints in Phase 2 were overall response rate (ORR; blinded independent central review [BICR] per RECIST v1.1) and safety. At the updated data cut-off of 4 Mar 2022, 281 pts with RET fusion+ NSCLC had received pralsetinib 400mg, of whom 260 had measurable disease at baseline per BICR. The ORR was 63.1% in pts with prior platinum treatment and 77.6% in those who were systemic treatment-naïve (Table), consistent with earlier data cuts. Median overall survival was 44.3 months in pre-treated pts and not reached in treatment-naïve pts. In the safety population (n=281), median treatment duration was 15.0 months with a median relative dose intensity of 86.1%. The most common (≥10%) grade ≥3 adverse events (AEs) were anaemia (23.1%), hypertension (17.8%), decreased neutrophil count (14.2%), pneumonia (12.8%) and neutropenia (10.7%). Overall, 10% of pts discontinued pralsetinib due to treatment-related AEs.Table: 1170PPrior platinum treatmentNo prior systemic treatmentMeasurable disease population (n=260)n=130n=107ORR, n (%) [95% CI]82 (63.1) [54.2–71.4]83 (77.6) [68.5–85.1]Median DOR, months (95% CI) Median follow-up, months38.8 (14.8–40.4) 29.313.4 (9.4–23.1) 20.2Efficacy population (n=281)n=141n=116Median PFS, months (95% CI) Median follow-up, months16.4 (11.4–22.3) 28.112.6 (9.2–16.6) 21.3Median OS, months (95% CI) Median follow-up, months44.3 (26.9–44.3) 29.4NR (31.9–NR) 22.1CI, confidence interval; DOR, duration of response; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival Open table in a new tab With additional follow-up, pralsetinib demonstrated robust and durable clinical activity in pts with advanced RET fusion+ NSCLC, including systemic treatment-naïve pts. No new or unexpected safety findings emerged from this updated data cut.