Merck and Gilead Sciences, Inc. announced the discontinuation of the Phase 3 KEYNOTE-D46/EVOKE-03 study investigating Gilead?s Trodelvy (sacituzumab govitecan-hziy) in combination with KEYTRUDA (pembrolizumab), Merck?s anti-PD-1 therapy, compared to KEYTRUDA monotherapy in certain patients with previously untreated metastatic non-small cell lung cancer, whose tumors expressed PD-L1 (tumor proportion score [TPS] =50%). The decision is based on the recommendation from the external Data Monitoring Committee (eDMC) following their review of the data from the pre-specified final analysis of progression-free survival (PFS) and interim analysis of overall survival (OS). A numerical improvement in PFS was observed, but did not reach statistical significance.

The probability of achieving statistically significant OS is unlikely at the planned final analysis. The safety profile of Trodelvy in combination with KEYTRUDA was consistent with the known safety of each agent. No new safety signals were identified with the combination.

These data will be presented at a future medical meeting. Regulatory authorities have been informed. Merck will inform study investigators of the recommendation from the DMC and advise patients in the study to speak to their physician regarding treatment.

There are no changes to ongoing Trodelvy or Merck studies. The companies are grateful to the patients, families, and healthcare professionals who participated in the KEYNOTE-D46/EVOKE-03 study and contributed to this important work. Trodelvy is a registered trademark of Gilead Sciences, Inc., or its related companies.

Lung cancer is one of the most common cancers worldwide, with an estimated 2.5 million new cases reported globally in 2022. Non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85% of lung cancers, and nearly half of these NSCLC patients are diagnosed only after the disease has spread, when treatment options are more limited and long-term survival remains low. Despite treatment advances, the 5-year survival rate for metastatic NSCLC is less than 10%.

While immunotherapy, with or without chemotherapy, is a standard first treatment option, it does not work for everyone, and new treatment options are needed. The KEYNOTE-D46/EVOKE-03 study is a global, open-label, randomized Phase 3 trial, sponsored by Merck, evaluating the efficacy and safety of Trodelvy (sacituzumab govitecan-hziy) in combination with KEYTRUDA (pembrolizumab) compared with KEYTRUDA monotherapy in patients with previously untreated metastatic non-small cell lung cancer (mNSCLC) whose tumors express PD-L1 with a tumor proportion score (TPS) =50% and do not have sensitizing EGFR, ALK or ROS1 genomic alterations. Approximately 620 patients were enrolled across study sites worldwide.

Patients were randomized 1:1 to receive either Trodelvy (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) plus KEYTRUDA (200 mg intravenously on Day 1 of a 21-day cycle), or KEYTRUDA monotherapy (200 mg intravenously on Day 1 of a 21-day cycle). KEYTRUDA was administered for up to 35 cycles, and Trodelvy was continued until disease progression, death, unacceptable toxicity or another treatment discontinuation criterion was met. The dual primary endpoints of the study are progression-free survival (PFS) as assessed by blinded independent central review (BICR) according to RECIST v1.1, and overall survival (OS).

Secondary endpoints include objective response rate (ORR), duration of response (DOR), patient-reported outcomes (PROs) and safety. Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers.

Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect. Trodelvy is currently approved in more than 60 countries for second-line or later metastatic triple-negative breast cancer (TNBC) and in more than 50 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer (mBC).

Healthcare professionals have well-established experience with Trodelvy, which has shown generally consistent outcomes across both clinical trials and real-world use in more than 75,000 breast cancer patients across 60+ countries. Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2- breast cancer?including in curative settings?as well as in small cell lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.