Researchers determined that the phase 3 EVOKE-01 trial failed to meet its primary end point of significantly improved OS with sacituzumab govitecan in patients with pretreated non-small cell lung cancer compared with docetaxel.
Compared with docetaxel, sacituzumab govitecan-hziy (Trodelvy) did not significantly improve overall survival (OS) in patients with metastatic or advanced non–small cell lung cancer (NSCLC) who were previously treated with chemotherapy and checkpoint inhibition.
These findings led to the failure of meeting the primary end point of the phase 3 EVOKE-01 trial (NCT05089734), according to an update from Gilead Sciences.1
At the time of prespecified analysis, the agent produced a numerical improvement in OS for patients with both squamous and nonsquamous histology. In the 60% of patients who did not respond to their last prior PD-(L)1 therapy, the median OS was numerically improved by over 3 months vs docetaxel; this magnitude of benefit was not observed in patients who achieved a response on their last prior PD-(L)1 therapy. Regarding safety, the agent was generally well tolerated, and no new safety signals were identified in this population.
Complete results from EVOKE-01 will be presented at an upcoming medical meeting, and a review of these findings with regulatory bodies is anticipated. Further exploration of potential pathways for sacituzumab govitecan is also planned in this patient population, given their high unmet medical need.
“The totality of our data gives us continued confidence in [sacituzumab govitecan’s] potential in metastatic NSCLC, and in our broader lung cancer clinical development program,” Merdad Parsey, MD, PhD, chief medical officer of Gilead Sciences, stated in a news release. “Treating [patients with] metastatic NSCLC that has progressed on or after platinum-based chemotherapy presents significant challenges and the need for safe and effective treatments remains urgent. We will work to further identify the metastatic NSCLC patient populations that may benefit from [sacituzumab govitecan].”
EVOKE-01 is a global, multi-center, open-label study enrolling patients at least 18 years old with pathologically documented stage IV NSCLC who have experienced disease progression following combination or sequential platinum-based chemotherapy and immune checkpoint inhibitor therapy. Notably, patients with known EGFR, ALK, or other actionable genomic alterations were eligible to enroll onto the study if they had previously received at least 1 available TKI. Other key inclusion criteria were an ECOG performance status of 0 or 1, adequate hematologic counts, and adequate hepatic function.1,2
Patients were not eligible for study inclusion if they had mixed small cell and NSCLC histology, had not recovered from adverse effects from prior therapies, an active second malignancy, clinically severe pulmonary compromise, active cardiac disease, active serious infection, known central nervous system metastases, or active chronic inflammatory bowel disease.2
A total of 603 patients were enrolled onto the study and randomly assigned in a 1:1 ratio to receive 10 mg/kg of sacituzumab govitecan on days 1 and 8 of a 21-day cycle vs 75 mg/m2 of docetaxel on day 1 of a 21-day cycle. Treatment continued until progressive disease or unacceptable toxicity.1,2
The study’s primary end point is OS. Key secondary end points include progression-free survival, objective response rate (ORR), duration of response (DOR), and disease control rate (DCR) as assessed by investigators per RECIST v1.1 criteria, and safety. Other secondary efficacy end points include time to first deterioration in shortness of breath domain as measured by NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) Score and time to first deterioration in NSCLC-SAQ Total Score.1
Previously reported data from the EVOKE-02 trial (NCT05186974) demonstrated a 56% ORR and 82% DCR among 61 patients with metastatic NSCLC in 2 cohorts of the trial who were treated with sacituzumab govitecan and pembrolizumab (Keytruda) in the first-line setting. In cohort A, 29 patients with a tumor proportion score (TPS) of at least 50% achieved an ORR of 69% with a DCR of 86%. In cohort B, 32 patients with a TPS of less than 50% achieved an ORR of 44% and a DCR of 78%. The median DOR was not reached at the time of data cut-off, and the DOR rate at 6 months was 88% in both cohorts.3
These preliminary data support Gilead’s ongoing phase 3 EVOKE-03 trial (NCT05609968) of sacituzumab govitecan and pembrolizumab vs pembrolizumab monotherapy in the first line for patients with PD-L1–high metastatic NSCLC. This study is currently open to enrollment.1
This first-in-class TROP-2-directed antibody-drug conjugate has been approved in almost 50 countries, with multiple additional regulatory reviews underway across the globe. The agent is currently indicated by the FDA for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who received 2 or more prior systemic therapies; unresectable locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer who previously progressed on endocrine-based therapy and 2 or more systemic therapies in the metastatic setting; and locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and a PD-(L)1 inhibitor.
Several other evaluations of sacituzumab govitecan are underway for various TNBC, HER2-negative, and urothelial cancer populations, as well as metastatic NSCLC, head and neck cancer, gynecological cancer, and gastrointestinal cancers.