CHICAGO — Enfortumab vedotin appeared well tolerated in patients with locally advanced or metastatic urothelial cancer who were previously treated with checkpoint inhibitors, according to data presented at the ASCO Annual Meeting.
Jonathan E. Rosenberg, MD, Enno W. Ercklentz Chair of genitourinary oncology service at Memorial Sloan Kettering Cancer Center, and colleagues evaluated the safety and efficacy of the antibody-drug conjugate enfortumab vedotin (ASG-22ME; Seattle Genetics, Astellas) for the treatment of metastatic urothelial carcinoma.
The analysis included data from 112 patients (median age, 67 years; 73% men) who received 1.25 mg/kg of IV enfortumab vedotin on days 1, 8, and 15 every 28 days.
Almost half of the patients (48%) had lung metastases at baseline, and 29% had liver metastases.
Almost all patients (94%) received at least one prior platinum-based therapy, and 79% had received at least one prior checkpoint inhibitor.
The most common all-grade adverse events included fatigue (54%), alopecia (45%) and decreased appetite (40%).
Anemia (8%), hyponatremia (7%) and urinary tract infection (7%) were the most common grade 3 or higher adverse events.
Grade 5 adverse events that were considered treatment-related included diabetic ketoacidosis, multiple organ dysfunction syndrome, respiratory failure and urinary tract obstruction.
Enfortumab vedotin induced a response in 41% (95% CI, 31.9-50.8) of patients, with partial responses occurring in 37% of patients.
Researchers observed a response in 39% (95% CI, 22.9-57.9) of patients with liver metastases, and a response in 43% (95% CI, 23.2-65.5) of patients who did not receive a prior checkpoint inhibitor.
“I think most compellingly, although a smaller cohort, patients with liver metastases had a confirmed objective response rate of 39%, something we do not generally see in urothelial cancer trials,” Rosenberg said during his presentation.
Median PFS was 5.4 months (95% CI, 5.1-6.2) in all patients treated with enfortumab vedotin.
Median OS among all patients was 13.6 months (95% CI, 11-15.4) and 14 months (95% CI, 11-16.1) in patients previously treated with at least one checkpoint inhibitor.
Rosenberg said that it was important to note that the survival data is not complete, considering that 58 patients were alive at the cutoff point and had not yet reached a median.
Additionally, Rosenberg said that the median OS data was encouraging.
“The preliminary OS of 14 months is encouraging given historical median OS for checkpoint inhibitors reported between 8.9 months and 10.3 months in patients after platinum-based chemotherapy,” he said.
The FDA has granted enfortumab vedotin breakthrough therapy designation as a result of this preliminary data, according to Rosenberg. – by Ryan McDonald
Rosenberg JE, et al. Abstract 4504. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Rosenberg reports stock and ownership interests with Illumina and Merck; honoraria with AstraZeneca and Bristol-Myers Squibb; consulting and advisory roles with Agensys, AstraZeneca, Bayer, Bristol-Myers Squibb, EMD Serono, Inovio Pharmaceuticals, Eli Lilly, Merck, Roche/Genentech, Sanofi and Seattle Genetics.