The antibody-drug conjugate sacituzumab govitecan will be evaluated vs single-agent docetaxel during the phase 3 EVOKE-01 trial in patients with metastatic non–small cell lung cancer.
The antibody-drug conjugate sacituzumab govitecan-hziy (Trodelvy) will be evaluated vs single-agent docetaxel during the phase 3 EVOKE-01 trial (NCT05089734) in patients with metastatic non–small cell lung cancer (NSCLC) who have progressed on or after platinum-based chemotherapy and immune checkpoint inhibitor (ICI) therapy.1
According to a trial overview presented in a poster during the 2022 World Conference on Lung Cancer, the primary end point of the open-label, global, multicenter, randomized trial is to determine if sacituzumab govitecan will provide an overall survival (OS) benefit vs docetaxel in this patient population.
“Current standard first-line treatments for patients with metastatic NSCLC that lacks an actionable mutation include ICI therapy, platinum-based chemotherapy, or a combination of the two; however, many patients either fail to respond to these therapies or develop progressive disease,” lead study author Niels Reinmuth, MD, PhD, the leader of the Thoracic Oncology Department at the Asklepios Lung Clinic in Germany, and colleagues, wrote in the poster.
Previously reported data from the phase 1/2 IMMU-132-01 basket study (NCT01631552) showed that single-agent sacituzumab govitecan produced a median OS of 9.5 months, an overall response rate (ORR) of 16.7%, and a manageable safety profile in patients with metastatic NSCLC, including 59% who received at least 3 prior lines of therapy.
EVOKE-01 will enroll patients who are at least 18 years old with pathologically documented stage IV NSCLC who have experienced disease progression following a platinum-based chemotherapy and ICI therapy, either given in combination or sequentially. Notably, patients with known actionable mutations will be permitted to enroll if they have received targeted therapy with at least 1 approved TKI. Patients will be required to undergo testing for EGFR and ALK mutations, plus PD-L1 status.
Additional inclusion criteria include an ECOG performance status of 0 or 1, adequate hematologic counts without transfusion or growth-factor support within 2 weeks of the start of the trial, a creatine clearance of at least 30 mL/min, and adequate hepatic function.
Key inclusion criteria will include mixed small cell lung cancer and NSCLC histology; prior treatment with an anticancer biologic agent within 4 weeks of enrollment; prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 2 weeks of enrollment; prior treatment with topoisomerase 1 inhibitors, TROP2-targeted therapy, or docetaxel at any time; unresolved adverse effects due to a previous treatment; known secondary malignancies or cardiac disease; active central nervous system metastases or carcinomatous meningitis; active chronic inflammatory bowel disease or gastrointestinal perforation within 6 months of enrollment; or the presence of an active serious infection requiring treatment.
The study will enroll approximately 520 patients who will be randomized 1:1 to receive 10 mg/kg of intravenous (IV) sacituzumab govitecan on days 1 and 8 of each 21-day cycle or 75 mg/m2 of IV docetaxel on day 1 of every 21-day cycle. Patients will remain on their respective treatment until progression or unacceptable toxicity. Stratification factors include histology (squamous vs nonsquamous), response to last prior ICI therapy (progressive disease/stable disease vs complete response/partial response), and prior targeted therapy for an actionable genomic alteration (yes vs no).
Secondary end points include investigator-assessed progression-free survival, ORR, duration of response, and disease control rate, per RECIST v1.1 criteria. Safety and tolerability, plus quality of life, will also serve as secondary end points.
Enrollment for EVOKE-01 began in November 2021 and is ongoing with 220 active sites open as of July 2022, and the trial is expected to expand approximately 250 sites across Asia, Australia, Europe, North America, and South America.
In April 2021, the FDA granted regular approval to sacituzumab govitecan for the treatment of with unresectable locally advanced or metastatic triple-negative breast cancer who have previously received 2 or more systemic therapies, including at least 1 of them for metastatic disease.2 Later in April 2021, the FDA granted an accelerated approval to sacituzumab govitecan for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor.3