KEYNOTE-D46/EVOKE-03 Discontinued After Missing Progression-Free Survival End Point

Following a recommendation from the external Data Monitoring Committee, Merck and Gilead Sciences have discontinued the phase 3 KEYNOTE-D46/EVOKE-03 trial after sacituzumab govitecan (Trodelvy®; Gilead) plus pembrolizumab (Keytruda®; Merck) failed to achieve a statistically significant progression-free survival (PFS) benefit in previously untreated patients with metastatic non-small cell lung cancer (NSCLC).

In this open-label trial, 620 previously untreated patients with metastatic NSCLC whose tumors expressed PD-L1 and lacked sensitizing EGFR, ALK, or ROS1 alterations were randomized 1:1 to receive either 10 mg/kg of sacituzumab govitecan on days 1 and 8 plus 200 mg of pembrolizumab on day 1 of each 21-day cycle or pembrolizumab monotherapy. Pembrolizumab was administered for up to 35 cycles, and sacituzumab govitecan was continued until disease progression, unacceptable toxicity, death, or another treatment discontinuation criterion was met. The dual primary end points were PFS and overall survival (OS). Key secondary end points included objective response rate (ORR), duration of response, patient-reported outcomes, and safety.

At analysis, a numerical improvement in PFS was observed with the combination however, the difference did not reach statistical significance. In addition, the probability of achieving a statistically significant OS benefit at the planned final analysis was considered unlikely. Safety was consistent with the known safety profiles of both agents, and no new safety signals were identified.

Regulatory authorities have been notified, and investigators will be informed of the Data Monitoring Committee recommendation. The companies stated that there will be no changes to other ongoing studies evaluating sacituzumab govitecan or pembrolizumab. Data from KEYNOTE-D46/EVOKE-03 are expected to be presented at a future medical meeting.

Source: 

MERCK. Merck and Gilead provide update on phase 3 KEYNOTE-D46/EVOKE-03 study. Accessed on: June 11, 2026. https://www.merck.com/news/merck-and-gilead-provide-update-on-phase-3-keynote-d46-evoke-03-study/