Merck and Gilead discontinue Phase 3 KEYNOTE‑D46/EVOKE‑03 (Trodelvy + KEYTRUDA) in PD‑L1 ≥50% mNSCLC
- The external Data Monitoring Committee recommended discontinuation of the Phase 3 KEYNOTE‑D46/EVOKE‑03 study after review of the pre‑specified final PFS and interim OS analyses.
- A numerical improvement in progression‑free survival was observed but did not reach statistical significance; the probability of achieving statistically significant overall survival at the planned final analysis was judged unlikely.
- The safety profile of sacituzumab govitecan (Trodelvy) combined with pembrolizumab (KEYTRUDA) was consistent with known profiles and no new safety signals were identified.
- Approximately 620 patients were enrolled in the global, randomized 1:1 trial in previously untreated metastatic NSCLC with PD‑L1 TPS ≥50%; dual primary endpoints were BICR‑assessed PFS (RECIST v1.1) and OS.
Study status
Merck and Gilead have discontinued the Phase 3 KEYNOTE‑D46/EVOKE‑03 study following a recommendation from the external Data Monitoring Committee (eDMC), based on their review of the data from the pre‑specified final analysis of progression‑free survival (PFS) and an interim analysis of overall survival (OS).
Efficacy and safety findings
A numerical improvement in PFS was observed with sacituzumab govitecan (Trodelvy) plus pembrolizumab (KEYTRUDA) versus KEYTRUDA monotherapy, but the result did not reach statistical significance. The eDMC concluded the probability of achieving statistically significant OS at the planned final analysis is unlikely. The safety profile of the combination was consistent with the known safety of each agent and no new safety signals were identified. These data will be presented at a future medical meeting.
Operational next steps
Regulatory authorities have been informed. Merck will notify study investigators of the eDMC recommendation and advise patients in the study to speak with their physicians regarding treatment. The companies stated there are no changes to ongoing Trodelvy or Merck studies.
Study design
KEYNOTE‑D46/EVOKE‑03 was a global, open‑label, randomized Phase 3 trial sponsored by Merck evaluating Trodelvy (sacituzumab govitecan‑hziy) plus KEYTRUDA (pembrolizumab) versus KEYTRUDA alone in previously untreated metastatic non‑small cell lung cancer patients whose tumors express PD‑L1 (TPS ≥50%) and lack sensitizing EGFR, ALK or ROS1 alterations; approximately 620 patients were enrolled and co‑primary endpoints were BICR‑assessed PFS (RECIST v1.1) and OS.
Source: Merck