Investigators Halt Phase 3 Trial of Sacituzumab Govitecan Combo in NSCLC

Developers at Merck have discontinued the phase 3 KEYNOTE-D46/EVOKE-03 study (NCT05609968) assessing sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) among patients with previously untreated metastatic PD-L1–positive non–small cell lung cancer (NSCLC), according to a press release.¹

The decision to terminate the trial came from a recommendation from the external data monitoring committee following an assessment of pre-specified final analysis data for progression-free survival (PFS) and interim analysis data for overall survival (OS). Although the sacituzumab govitecan combination numerically improved PFS, the outcomes did not reach statistical significance. Additionally, the evaluation showed that OS was unlikely to achieve statistical significance at the planned final analysis.

The safety profile of sacituzumab govitecan in the phase 3 trial was comparable with prior reports of the agent; investigators observed no new safety signals. The data are planned for presentation at a medical meeting in the future.

Developers will inform the study investigators of the monitoring committee’s recommendation and advise patients to speak with their physicians regarding therapy. This trial discontinuation does not affect the status of any other ongoing studies evaluating sacituzumab govitecan or pembrolizumab.

“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,” the developers noted in the press release.¹

Investigators designed KEYNOTE-D46/EVOKE-03 as an international, open-label, phase 3 trial to assess the safety and efficacy of adding sacituzumab govitecan to pembrolizumab compared with pembrolizumab monotherapy among those with previously untreated metastatic NSCLC harboring a PD-L1 TPS of at least 50%. Approximately 620 patients were randomly assigned 1:1 to receive sacituzumab govitecan at 10 mg/kg intravenously on days 1 and 8 of each 21-day cycle plus pembrolizumab at 200 mg intravenously on day 1 of each cycle or the same dose of pembrolizumab alone. Patients received pembrolizumab for a maximum of 35 cycles, and investigators administered sacituzumab govitecan until progressive disease, death, unacceptable toxicity, or other discontinuation criteria were fulfilled.

The trial’s dual primary end points were PFS per blinded independent central review using RECIST v1.1 criteria and OS. Secondary end points included objective response rate, duration of response, patient-reported outcomes, and safety.

Patients 18 years and older histologically or cytologically confirmed metastatic NSCLC; a lack of targetable EGFR, ALK, or ROS1 alterations; and a PD-L1 TPS of at least 50% per immunohistochemistry were eligible for enrollment on the trial.² Having a minimum life expectancy of 3 months was an additional requirement for entering the study.

Those with a history of a second malignancy, prior systemic chemotherapy or other targeted antineoplastic agents for metastatic NSCLC, prior treatment with topoisomerase 1 inhibitors, or prior radiotherapy within 2 weeks of beginning study intervention were ineligible for enrollment on the trial. Patients were also unable to enroll if they had cardiac disease, active chronic inflammatory bowel disease, known active central nervous system (CNS) metastases and/or carcinomatous meningitis, active autoimmune disease requiring systemic therapy within 2 years of study entry, or active infection requiring systemic therapy.

Developers designed sacituzumab govitecan as a Trop-2–directed antibody drug conjugate with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase 1 inhibitor payload. Investigators are currently evaluating sacituzumab govitecan across several phase 3 trials among patients with tumors harboring high Trop-2 expression, including in triple-negative breast cancer, small cell lung cancer, and gynecologic cancers.

References

1. Merck and Gilead provide update on phase 3 KEYNOTE-D46/EVOKE-03 study. News release. Merck. June 8, 2026. Accessed June 10, 2026. https://tinyurl.com/2s4j49uh
2. Study of pembrolizumab (MK-3475) monotherapy versus sacituzumab govitecan in combination with pembrolizumab for participants with metastatic non-small cell lung cancer (NSCLC) With programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% (MK-3475-D46). ClinicalTrials.gov. Updated December 24, 2025. Accessed June 10, 2026. https://tinyurl.com/5n6rwnzs