2025-06-02-Jefferies-ASCO25_ALK+_ROS1+非小细胞肺癌（NSCLC）格局更新_13页_3mb

ASCO25 ALK+ and ROS1+ NSCLC Landscape Updates

This report summarizes the incremental updates for ALK-positive and ROS1-positive non-small cell lung cancer (NSCLC) from the ASCO25 conference:

• ALK Updates:

  • The lorlatinib CROWN Study post-hoc analysis shows that tumor response depth correlates with progression-free survival (PFS) benefits, with median PFS not reached at 5 years; a follow-up update is planned in 7 years. Approximately 1/3 of patients experienced dose modifications for on-target AEs, with unresolved AEs in ~20-25% of cases.
  • Real-world evidence from RWD indicates that patients and caregivers prioritize PFS benefit as the primary factor when choosing therapies, with a willingness to accept higher side effect risks for prolonged survival.
  • Upfront 2G/3G ALK tyrosine kinase inhibitors (TKIs) show less on-target resistance compared to use after crizotinib, but off-target mutations are more frequent.
  • Iruplinalkib demonstrates promising efficacy in real-world data, with a 27% objective response rate (ORR) in heavily pretreated patients, all of whom previously received lorlatinib.
  • Comparative RWD shows that transitioning to second-line (2L) therapies occurs less frequently in practice (~25%) than in clinical trials.

• ROS1 Updates:

  • Taletrectinib pooled analysis confirms consistent efficacy across regions and races, with adverse event (AE) profile dominated by gastrointestinal (GI) toxicities (early in treatment) and elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels.

For investment, Jefferies maintains a BUY recommendation on Nuvalent Inc (NUVL) for its compounds Neladalkib (ALK) and Zidesamitinib (ROS1). Zidesamitinib is expected to generate 2L pivotal data in 2Q25, supporting potential 2026 approval and commercial launch. Nuvalent's valuation is DCF-based, with risks centered on clinical, regulatory, and commercial factors.

Bottom Line: ASCO25 provided mostly post-hoc analyses and real-world learnings for ALK+ and ROS1+ NSCLC, reinforcing the drug profiles of targeted therapies with continued investor interest, particularly for upcoming pivotal data.