Sacituzumab Govitecan Monotherapy for NSCLC Disappoints in EVOKE-01 Trial Update

The most recent update on sacituzumab govitecan-hziy (Trodelvy; Gilead) for non–small cell lung cancer (NSCLC) from the phase 3 EVOKE-01 trial (NCT05089734) shows the TROP-2–directed antibody drug conjugate was not able to meet its primary end point of improved overall survival (OS) in patients.¹

EVOKE-01 is currently investigating the agent as monotherapy vs docetaxel to treat metastatic or locally advanced NSCLC that has failed platinum-based chemotherapy and checkpoint inhibitor therapy, and key secondary end points are progression-free survival, objective response rate, duration of response, and disease control rate per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and safety.^1,2

According to the announcement from Gilead, although OS was improved by more than 3 months in patients with squamous and nonsquamous histology who had not responded to their immediate previous anti–programmed death-ligand 1 (PD-L1) line of treatment (60% of the overall trial population), a similar improvement was not seen in the patients who had a response to their previous anti–PD-L1 treatment; Gilead will continue to investigate potential roles for sacituzumab govitecan in this latter patient group. The positive findings that did come from this most recent analysis regarded sacituzumab govitecan’s safety profile, in that no new safety signals were seen, and patients continue to be able to tolerate the treatment well.¹

Merdad Parsey, MD, PhD, Gilead’s chief medical officer, underscores that this setback has not deterred the pharma giant’s determination to make inroads against metastatic NSCLC and to expand its broader lung cancer clinical development program.

“Treating metastatic NSCLC that has progressed on or after platinum-based chemotherapy presents significant challenges and the need for safe and effective treatments remains urgent,” he states. “We will work to further identify the metastatic NSCLC patient populations that may benefit from Trodelvy.”¹

NSCLC and lung cancer in general continue to present a challenge to clinicians worldwide. Although the former is typically diagnosed at an earlier stage vs small cell lung cancer,³ Gilead notes that most cases of first-line metastatic NSCLC progress and the response rate to frontline immunotherapies only comes in at 35% to 55%, with limited subsequent treatment options.¹

Sacituzumab govitecan has current indications for metastatic breast cancer, metastatic triple-negative breast cancer, and metastatic or locally advanced urothelial cancer⁴; it is also currently being investigated as a combination treatment with pembrolizumab or pembrolizumab plus carboplatin or cisplatin in the phase 2 EVOKE-02 trial (NCT05186974) and in combination with pembrolizumab vs pembrolizumab monotherapy in the phase 3 EVOKE-03 trial (NCT05609968).^5,6

“Based on strong preliminary efficacy and safety data from the phase 2 EVOKE-02 study of Trodelvy in combination with pembrolizumab, presented at the World Conference on Lung Cancer 2023, Gilead remains confident in its ongoing phase 3 EVOKE-03 study in [first-line] metastatic PD-L1–high NSCLC,” the Gilead statement adds. “The EVOKE-03 study is currently enrolling.”¹

References

1. Gilead provides update on phase 3 EVOKE-01 study. News release. Gilead Sciences. January 22, 2024. Accessed January 23, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/1/gilead-provides-update-on-phase-3-evoke-01-study
2. Study of sacituzumab govitecan (sg) versus docetaxel in participants with advanced or metastatic non-small cell lung cancer (NSCLC) (EVOKE-01). ClinicalTrials.gov. Updated December 7, 2023. Accessed January 23, 2024. https://clinicaltrials.gov/study/NCT05089734
3. Stages of non–small cell and small cell lung cancer. Memorial Sloan Kettering Cancer Center. Accessed January 23, 2024. http://tinyurl.com/45e32p8n
4. McNulty R. First-line sacituzumab govitecan plus pembrolizumab shows promising early activity in NSCLC. The American Journal of Managed Care^®. September 30, 2023. Accessed January 23, 2024. https://www.ajmc.com/view/first-line-sacituzumab-govitecan-plus-pembrolizumab-shows-promising-early-activity-in-nsclc
5. Study of sacituzumab govitecan combinations in first-line treatment of participants with advanced or metastatic non-small-cell lung cancer (NSCLC) (EVOKE-02). ClinicalTrials.gov. Updated October 2, 2023. Accessed January 23, 2024. https://clinicaltrials.gov/study/NCT05186974
6. 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 January 19, 2024. Accessed January 23, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05609968