27P Durability of efficacy and safety with selpercatinib in patients (pts) with RET fusion+ non-small cell lung cancer (NSCLC)

Selpercatinib, a first-in-class highly selective and potent CNS-active RET kinase inhibitor, is approved in multiple countries for treatment of RET fusion+ NSCLC. In prior reports, follow-up was limited and duration of response (DoR) and progression-free survival (PFS) were ongoing and immature. Updated analysis of selpercatinib in pts with RET fusion+ NSCLC in LIBRETTO-001 (NCT03157128) was conducted with a 15-month (mo) interval between the preceding and current analyses. Primary endpoint was objective response rate (ORR, RECIST 1.1) by independent review committee (IRC). Secondary endpoints included DoR, PFS, clinical benefit rate (CBR; CR+PR+SD ≥16 weeks), OS, and safety. Efficacy results from treatment naïve pts (N=69) and pts previously treated with platinum chemotherapy (N=247) are shown (Table). Despite a median follow-up (f/u) of ∼24 mo in the treatment naïve and platinum chemotherapy pretreated populations, median DoR (mDoR) and PFS (mPFS) estimates are still not mature. Among all NSCLC pts, 26 had measurable CNS metastases at baseline per IRC. Selpercatinib treatment resulted in a CNS ORR of 84.6% (95% CI: 65.1–95.6), with a CNS mDoR of 9.4 mo (95%CI: 7.4–15.3) at a median f/u of 25.8 mo. In the safety population (NSCLC pts with ≥ 1 dose, N=356), the most common adverse events (AEs in ≥25% pts) were dry mouth, diarrhea, hypertension, increased ALT/AST, peripheral edema, constipation, rash, headache, and fatigue. In total, 34 pts (9.6%) discontinued treatment due to AEs, including 11 pts (3.1%) due to drug-related AEs per investigator.Table: 27PBy IRCPrior platinum chemotherapyTreatment naïve% (95% CI)30Mar20 N=21815Jun21 N=24730Mar20 N=4815Jun21 N=69ORR56.9 (50.0–63.6)61.1 (54.7–67.2)85.4 (72.2–93.9)84.1 (73.3–91.8)CBR84.4 (78.9–89.0)85.4 (80.4–89.6)93.8 (82.8–98.7)92.8 (83.9–97.6)mDoR, mo (95% CI)17.5 (12.1–NE)28.6 (20.4–NE)NE (12.0–NE)20.2 (13.0–NE)Censoring, %69.460.975.655.2Median f/u, mo12.021.29.820.312mo DoR69.1 (58.1–77.8)73.1 (64.9–79.7)65.0 (42.8–80.3)66.1 (51.6–77.3)mPFS, mo (95% CI)19.3 (16.5–NE)24.9 (19.3–NE)NE (13.8–NE)22.0 (13.8–NE)Censoring, %66.155.970.853.6Median f/u, mo13.624.710.821.912mo PFS69.7 (62.2–75.9)70.5 (64.1–76.0)67.6 (49.5–80.3)70.6 (57.8–80.2) Open table in a new tab With longer follow-up and additional patients, selpercatinib demonstrates durable efficacy and intracranial activity regardless of line of therapy. The safety profile of selpercatinib remains consistent with prior reports.