High rates of durable responses with sacituzumab govitecan plus pembrolizumab as first-line treatment for patients with metastatic non-small cell lung cancer

Preliminary results of the phase II EVOKE-02 study demonstrate encouraging efficacy of sacituzumab govitecan in combination with pembrolizumab in the first-line treatment of patients with previously untreated metastatic non-small cell lung cancer. The combination induced high rates of durable responses with a manageable safety profile, irrespective of the level of PD-L1 expression.

Background

In recent years, programmed death (ligand) 1 (PD-[L]1) inhibitor-based regimens have been established as the standard of care first-line treatment for patients with metastatic non-small cell lung cancer (mNSCLC). However, novel treatment combinations are needed to further improve outcomes for patients. Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate with proven clinical activity and a manageable safety in previously treated patients with mNSCLC. Based on these earlier findings, the global, open-label, multicohort, Phase II EVOKE-02 study is evaluating the combination of SG and pembrolizumab (pembro) with or without a platinum agent as first-line treatment for patients mNSCLC. During the 2023 WCLC meeting, preliminary results were presented for patients treated with SG + pembro in Cohorts A and B of the study.

Study design

Cohorts A or B of EVOKE-02 enrolled previously untreated mNSCLC patients without actionable genomic alterations and an ECOG performance status of 0 or 1. Patients with a PD-L1 tumour proportion score (TPS) ≥50% were allocated to Cohort A, whereas patients with a PD-L1 TPS <50% were grouped in Cohort B. Patients in both cohorts received SG at a dose of 10 mg/kg on days 1 and 8 and pembrolizumab (200 mg) on day 1 of 21-day cycles. The trial endpoints include objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), duration of response (DoR), disease control rate (DCR), overall survival (OS) and safety. At WCLC 2023, safety results were reported in the safety-evaluable patients who received at least one dose of study treatment in combination with efficacy results in the efficacy-evaluable patient cohort, consisting of patients with at least 13 weeks of follow-up.

Results

In total, 63 patients were enrolled in the study (30 in cohort A, 33 in cohort B). The median age of patients in the trial was 68 years, about 80% was male and 60% had a non-squamous tumour histology. In cohort B, half of the patients had a PD-L1 expression of 1-49%, while the remaining 50% had a PD-L1 expression <1% (in cohort A 100% ≥50% per protocol). At the time of the analysis, the median number of treatment cycles with SG and pembro was 6 in both arms. In cohort A, 37% of patients had discontinued all study treatment as compared to 58% in cohort B. Overall, the ORR with SG + pembro was reported at 56% (69% in cohort A, 44% in cohort B), with a DCR of 82% (86% and 78% in cohorts A and B, respectively). The median DoR was not reached, with a 6-month DoR rate of 88% in both cohorts.

In the overall safety population (N=63), any-grade treatment-related adverse events (TRAEs) were reported in 90% of patients, reaching grade ≥3 in severity in 38%. Treatment-related serious AEs were reported in 14%. TRAEs led to discontinuation of SG or pembro in 14% and 13% of patients, respectively. Investigators reported one TRAE leading to death. The most common any-grade treatment emergent AEs consisted of diarrhoea (51%), anaemia (42%), asthenia (38%), and alopecia (37%). The most common grade ≥3 treatment emergent AE was neutropenia with an incidence of 16%.

Conclusions

SG + pembro demonstrated encouraging antitumour activity in the first-line treatment of patients with mNSCLC across PD-L1 subgroups with an ORR of 69% in Cohort A and 44% in cohort B. Responses lasted for at least 6 months in 88% of patients in both cohorts. The safety profile of SG + pembro was manageable and consistent with the known safety profile of both agents. As such, these preliminary results support further investigation of SG + pembro as a first-line treatment regimen for patients with mNSCLC. In this respect, the open-label, global, randomised, phase III EVOKE-03 study (NCT05609968) is currently comparing SG + pembro to pembro alone as first-line treatment for patients with mNSCLC and a PD-L1 TPS ≥ 50%.

Reference

Cho B, et al. Sacituzumab Govitecan + Pembrolizumab in 1L Metastatic Non-Small Cell Lung Cancer: Preliminary Results of the EVOKE- 02 Study. Presented at WCLC 2023; Abstract OA05.04.