Nuvalent (NUVL) European Society for Medical Oncology Congress (ESMO) 2024 summary

Key program updates and milestones

• Achieved all 2024 milestones, including phase 2 trial initiations for both ROS1 (ARROS-1) and ALK (ALCOVE-1) programs, and HER2 phase 1 trial initiation.

• Both lead programs received FDA breakthrough therapy designations and presented updated phase 1 data at ESMO 2024.

• Enrollment momentum is strong: 331 patients in ARROS-1 and 362 in ALCOVE-1 as of September 2024.

• Pivotal phase 2 data for both programs expected in 2025, with first potential product approval targeted for 2026.

• Announced ALCAZAR phase 3 trial for NVL-655 in frontline ALK-positive NSCLC, to start in 1H 2025.

Clinical data highlights: zidesamtinib (ROS1)

• Phase 1 ARROS-1 enrolled 104 heavily pretreated patients; 71 evaluable for response.

• ORR of 44% overall, 51% in refractory/naive, and 72% in G2032R mutation subset.

• Durable responses: median DOR not reached in most groups; 12.1 months in third-line+ patients.

• Intracranial ORR of 50% in patients with CNS lesions; no CNS progression among responders.

• Favorable safety profile with low rates of dose modification and no TRK-related neurotoxicity.

Clinical data highlights: NVL-655 (ALK)

• Phase 1 ALCOVE-1 enrolled 133 patients; 103 evaluable for response, 39 at RP2D (150 mg).

• ORR of 38% overall; 35% in patients with ≥2 prior ALK TKIs; 54% in compound ALK mutations.

• Lorlatinib-naive patients: ORR 53% overall, 88% with ALK-resistant mutations.

• Durable responses: median DOR 14.4 months in responders with ALK-resistant mutations; 100% six-month DOR at RP2D.

• Intracranial responses observed, including complete responses post-lorlatinib; no CNS progression among confirmed responders.

• Well-tolerated safety profile; most common AEs were ALT/AST increases, constipation, dysgeusia, and nausea.