Dr. Sabari on the EVOKE-02 Trial With Sacituzumab Govitecan in NSCLC

Joshua K. Sabari, MD, assistant professor, Department of Medicine, NYU Grossman School of Medicine, NYU Langone Health’s Perlmutter Cancer Center, discusses the ongoing phase 2 EVOKE-2 trial (NCT05186974) investigating sacituzumab govitecan-hziy (Trodelvy) in non– small cell lung cancer (NSCLC); emerging data on antibody-drug conjugates (ADCs) in the second– or first-line treatment setting; and the planned phase 3 EVOKE-03 trial (NCT05609968) of sacituzumab govitecan plus pembrolizumab (Keytruda) as a frontline treatment.

The EVOKE-02 study is a global, open-label, multi-center, phase 2 trial designed to assess the combination of sacituzumab govitecan and pembrolizumab, with or without chemotherapy, irrespective of PD-L1 expression, Sabari begins. The study included patients with advanced or metastatic NSCLC who lack actionable genomic alterations. Patients were assigned to 1 of 4 cohorts based on disease status and PD-L1 expression, Sabari details. Cohort A included patients with squamous/non-squamous NSCLC and a tumor proportion score (TPS) greater than or equal to 50%, while Cohort B included those with a TPS less than 50%. Patients in Cohorts A and B received the combination regimen.

After enrollment in a safety run-in cohort, patients will be assigned to Cohorts C or D based on disease status for carboplatin combinations. Cohort C will enroll patients with non-squamous NSCLC with any PD-L1 expression level, and Cohort D will enroll patients with squamous NSCLC with any PD-L1 expression level. Patients in Cohorts C or D received sacituzumab govitecan, pembrolizumab, and chemotherapy. The trial's primary end point was objective response rate.

Preliminary results from cohorts A and B of this trial were presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer, Sabari states. Results demonstrated that 56% of patients across both cohorts achieved an overall response rate (ORR) of 56% with sacituzumab govitecan and pembrolizumab, with a disease control rate of 82%, he reports. Notably, the ORR was 69% in the PD-L1 high cohort, and this cohort was limited to 30 patients, Sabari adds. Although complete PFS data are pending, the preliminary swimmer's plot suggests that these responses are also durable, he notes.

Limited ADC data in the frontline setting necessitates further exploration of these agents in NSCLC, Sabari continues. There is also a need for second-line studies like the phase 3 EVOKE-01 trial (NCT05089734), which compares sacituzumab govitecan vs docetaxel, he says. Concerns about ADC-associated toxicities impacting frontline use of the combination were somewhat alleviated in EVOKE-02, as the combination of sacituzumab govitecan and pembrolizumab did not significantly increase toxicities, Sabari explains. Expected adverse effects such as diarrhea or interstitial lung disease did not increase in frequency, demonstrating the safety of sacituzumab govitecan in combination with a PD-1 inhibitor, Sabari says.

Additionally, investigators anticipate data from the ongoing, open label, global, randomized, phase 3 EVOKE 03 trial (NCT05609968), Sabari states. This trial is currently evaluating sacituzumab govitecan and pembrolizumab vs pembrolizumab monotherapy as a first-line treatment for patients with metastatic NSCLC with PD-L1 TPS of at least 50%. Ongoing research in ADC combinations for frontline use in the PD-L1 high population will provide valuable insights into the evolving landscape of NSCLC treatment, Sabari concludes.