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 announced a phase 3 ALCAZAR trial for frontline ALK-positive NSCLC in 2025.

• Both lead programs, zidesamtinib (ROS1) and NVL-655 (ALK), received FDA breakthrough therapy designations and demonstrated strong enrollment momentum globally.

• Updated phase 1 data for zidesamtinib and NVL-655 presented at ESMO 2024 showed durable responses, CNS activity, and favorable safety profiles in heavily pretreated NSCLC patients.

• Pivotal phase 2 data readouts for both programs are expected in 2025, supporting potential global registration filings.

• The company remains on track for its first potential product approval in 2026, with a robust pipeline and ongoing regulatory engagement.

Clinical data highlights: zidesamtinib (ROS1)

• In phase 1, zidesamtinib showed a 44% ORR in heavily pretreated ROS1-positive NSCLC, with higher ORR in G2032R mutation (72%) and second-line post-crizotinib (73%).

• Durable responses observed: median DOR not reached in most subgroups, 12.1 months in third-line or beyond, and 67% 12-month DOR rate overall.

• Demonstrated CNS activity with 50% intracranial ORR and no CNS progression among responders.

• Safety profile was favorable, with low rates of dose modification and no discontinuations due to adverse events.

• Phase 2 enrollment exceeded 227 additional patients, with pivotal data expected in 2025.

Clinical data highlights: NVL-655 (ALK)

• In phase 1, NVL-655 achieved a 38% ORR in heavily pretreated ALK-positive NSCLC, with 54% ORR in patients with compound ALK mutations and 88% in lorlatinib-naive with ALK-resistant mutations.

• Durable responses: median DOR up to 14.4 months, with 100% six-month DOR at the recommended phase 2 dose in key subgroups.

• Demonstrated intracranial responses, including complete CNS responses in patients progressing on lorlatinib.

• Safety profile was consistent across doses, with most common adverse events being ALT/AST increases and low discontinuation rates.

• Phase 2 enrolled 229 additional patients, with pivotal data and phase 3 ALCAZAR trial initiation planned for 2025.