The antibody-drug conjugate enfortumab vedotin significantly improved overall survival versus chemotherapy in a phase 3 trial.
The antibody-drug conjugate (ADC) enfortumab vedotin-ejfv (Padcev) demonstrated a significant improvement in overall survival (OS) in one bladder cancer trial, and promising long-term OS data in another, according to recently reported results.
Findings from the phase 3 EV-301 trial showed that the ADC reduced the risk of death by 30% compared with chemotherapy in patients with locally advanced or metastatic urothelial cancer previously treated with platinum-based chemotherapy and a PD-1/PD-L1 inhibitor (HR, 0.70; P = .001).1 Enfortumab vedotin also reduced the risk of disease progression or death by 39% (HR, 0.61; P <.00001), according to a press announcement from Seattle Genetics and Astellas Pharma, the co-developers of the ADC.
Moreover, data from cohort 1 of the single-arm, phase 2 EV-201 trial presented during the 2020 ESMO Congress demonstrated OS rates of 50.4% at 12 months and 34.2% at 18 months with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer previously treated with platinum-based chemotherapy and immune checkpoint inhibitors.2
Cohort 1 of the pivotal phase 2 EV-201 trial (NCT03219333) included 125 patients with a median age of 69 years and a median of 3 prior systemic treatments. The median duration of treatment with the ADC was 4.6 months, with a maximum duration of treatment of 27.3 months (ongoing as of data cutoff).
The OS data from EV-201 presented during the 2020 ESMO Congress showed that at a median follow-up of 22.3 months, the median OS was 12.4 months.
Based on previously reported data from EV-201, the FDA granted enfortumab vedotin an accelerated approval in this setting in December 2019.3,4 The data the FDA reviewed showed an objective response rate of 44% with the ADC, comprising a 12% complete response rate and a 32% partial response rate. The median duration of response was 7.6 months.
The safety profile showed that the most common treatment-related adverse events (AEs) included alopecia (49.6%), fatigue (49.6%), and decreased appetite (44%). The most common treatment-related AEs that were grade 3 or higher included neutropenia (8.0%), anemia (7.2%), and fatigue (6.4%). Twelve percent of patients discontinued treatment due to AEs, with peripheral sensory neuropathy (6%) being the most common. The investigators did report 1 treatment-related death from interstitial lung disease, confounded by high-dose corticosteroid use and suspected Pneumocystis jiroveci pneumonia.
The EV-301 trial (NCT03474107) is the confirmatory trial for the accelerated approval of enfortumab vedotin, and the positive OS findings will support the co-developers’ application for a full FDA approval of the ADC.
The global, multicenter, open-label, phase 3 trial randomized patients to enfortumab vedotin or physician's choice of either docetaxel, paclitaxel, or vinflunine. The target enrollment was approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1 or PD-L1 inhibitor and platinum-based therapies. The primary end point was OS, with key secondary endpoints including progression-free survival, duration of response, ORR, safety, and QoL.
The most frequent (≥5% of patients) grade ≥3 AEs were rash, hyperglycemia, decreased neutrophil count, fatigue, anemia, and decreased appetite.
Given the OS benefit observed with enfortumab vedotin, patients randomized to the chemotherapy arm will now be eligible to receive enfortumab vedotin.
According to the co-developers, the data from EV-301 will be submitted for presentation at an upcoming scientific congress.
1. Seattle Genetics and Astellas Announce PADCEV® (enfortumab vedotin-ejfv) Significantly Improved Overall Survival in Phase 3 Trial in Previously Treated Locally Advanced or Metastatic Urothelial Cancer [news release]. Bothell, Washington and Tokyo. Published September 18, 2020. https://bwnews.pr/3343rxD. Accessed September 18, 2020.
2. O’Donnell MD, Galsky JE, Petrylak DP, et al. EV-201: Long-term results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial caner previously treated with platinum and PD-1/PD-L1 inhibitors. Poster presented at: European Society of Medical Oncology Virtual Congress 2020; September 17-20, 2020. Abstract 746P.
3. FDA grants accelerated approval to enfortumab vedotin-ejfv for metastatic urothelial cancer. FDA. Published December 18, 2019. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-enfortumab-vedotin-ejfv-metastatic-urothelial-cancer. Accessed September 18, 2020.
4. Rosenberg J, Sridhar SS, Zhang J, et al. EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma. J Clin Oncol. 2020;38(10):1041-1049. doi:10.1200/JCO.19.02044