First-Line Sacituzumab Govitecan Plus Pembrolizumab Shows Promising Early Activity in NSCLC

Combination sacituzumab govitecan-hziy (Trodelvy; Gilead) and pembrolizumab (Keytruda; Merck) showed promising early antitumor activity in patients with advanced or metastatic non­–small cell lung cancer (NSCLC) in the first-line setting, according to findings from the phase 2 EVOKE-02 trial (NCT05186974) announced in a press release and presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.¹

The ongoing, international, open-label, multicohort EVOKE-02 trial aims to assess whether adding sacituzumab govitecan, a TROP-2–directed antibody-drug conjugate, to frontline programmed cell death protein 1 (PD-1) inhibition with pembrolizumab can improve outcomes in previously untreated metastatic NSCLC with no actionable genomic alterations.² In a preliminary analysis of 61 treated patients, the objective response rate (ORR) was 56% (95% CI, 42%-69%) across cohorts A (programmed death-ligand 1 [PD-L1] tumor proportion score [TPS] ≥ 50%) and B (PD-L1 TPS < 50%), which included 29 and 32 patients, respectively.¹

“Patients with metastatic NSCLC continue to need novel treatment options. The data from the EVOKE-02 study gives us confidence in the clinical activity of sacituzumab govitecan in combination with pembrolizumab in first-line metastatic NSCLC patients,” Byoung Chul Cho, MD, PhD, professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine, said in a statement.¹ “The positive response rates and duration of response across patients treated with the combination shows promise compared with historical responses to anti-PD1 monotherapy in this setting. These data support further investigation of sacituzumab govitecan as a potential IO [immuno-oncology]-combination option in first-line metastatic NSCLC.”

Trial end points include ORR based on RECIST v1.1 criteria, progression-free survival, duration of response (DOR), disease control rate (DCR), overall survival, and safety. Cohorts A and B received combination sacituzumab govitecan and pembrolizumab as part of a safety run-in cohort, and the trial will enroll patients in 2 additional cohorts based on disease status to assess the immunotherapy agents plus chemotherapy.

The confirmed and unconfirmed ORR was 69% in Cohort A, and the DCR was 86%. In Cohort B, the confirmed and unconfirmed ORR was 44% and the DCR was 78%. At the time of the data cutoff, the DOR was not yet reached, but at 6 months, the rate of DOR was 88% across the cohorts.

“These data are very encouraging and confirms our approach for the ongoing phase 3 EVOKE-03 study of [sacituzumab govitecan] in combination with [pembrolizumab] vs [pembrolizumab] monotherapy for patients in first-line PD-L1–high metastatic NSCLC,” said Bill Grossman, MD, PhD, senior vice president and therapeutic area head at Gilead Oncology. “We look forward to potentially bringing a new treatment option to previously untreated metastatic NSCLC patients.”

Regarding safety, the profile of the combination treatment was consistent with those of each agent. Diarrhea (54%), anemia (48%), and asthenia (38%) were the most common treatment-emergent adverse events of any grade, and adding pembrolizumab to sacituzumab govitecan did not increase known safety events. However, 18% of patients discontinued treatment due to AEs and 1 treatment-related death occurred due to sepsis.

Sacituzumab govitecan is FDA approved for indications in hormone receptor–positive/HER2-negative metastatic breast cancer, metastatic triple-negative breast cancer, and metastatic urothelial cancer. Its uses in NSCLC and in combination with pembrolizumab are investigational.

References

1. Gilead’s phase 2 EVOKE-02 study of Trodelvy (sacituzumab govitecan-hziy) in combination with KEYTRUDA (pembrolizumab) demonstrates promising clinical activity in first-line metastatic non-small cell lung cancer. News release. Gilead. September 10, 2023. Accessed September 19, 2023. https://www.gilead.com/news-and-press/press-room/press-releases/2023/9/gileads-phase-2-evoke02-study-of-trodelvy-sacituzumab-govitecanhziy-in-combination-with-keytruda-pembrolizumab-demonstrates-promising-clinica

2. 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 August 21, 2023. Accessed September 20, 2023. https://clinicaltrials.gov/ct2/show/NCT05186974