Gilead's Trodelvy fails phase 3 trial in first-line lung cancer, narrowing the field for TROP2 antibody-drug conjugates

Merck & Co. and Gilead announced Monday that they are stopping the phase 3 Evoke-03 trial (also called Keynote-D46) after an external data monitoring committee's recommendation. The study, which evaluated Trodelvy combined with Keytruda versus Keytruda alone as a first-line treatment in patients with PD-L1-high NSCLC (non-small cell lung cancer), did not meet its progression-free survival endpoint at final analysis, and an interim overall survival analysis suggested the trial was unlikely to achieve statistical significance.

Trodelvy is a TROP2 antibody-drug conjugate (ADC)—a type of cancer therapy combining an antibody targeting a tumor protein with a chemotherapy drug. This latest failure follows a second-line NSCLC trial setback more than two years ago, significantly limiting the drug's commercial prospects outside triple-negative breast cancer.

Gilead's stock price dropped about 2.7% as of Tuesday morning publication. Without a first-line NSCLC win, Trodelvy's commercial value will depend mainly on breast cancer uses, which analysts view as insufficient to justify the $21 billion price tag Gilead paid for Immunomedics, the drug's developer.

Merck's rival TROP2 ADC, sac-TMT, remains in contention: a subgroup analysis of the OptiTROP-lung05 study showed sac-TMT combined with Keytruda linked to a 53% PFS benefit over Keytruda alone in Chinese patients with previously untreated PD-L1-high NSCLC. Merck's phase 3 TroFuse-007 study is testing that regimen in a global population. AstraZeneca and Daiichi Sankyo are also pursuing first-line NSCLC with their own TROP2 ADC, Datroway, in the phase 3 Avanzar trial expected to read out this year.