Frontline Enfortumab Vedotin Plus Pembrolizumab Elicits Responses in Advanced Urothelial Cancer

Enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) induced encouraging responses when used in the frontline treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are not eligible to receive cisplatin-based chemotherapy, according to findings from cohort K of the phase 1/2 EV-103 trial (NCT03288545).¹

Those who received the doublet experienced a confirmed objective response rate (ORR) of 64.5% (95% CI, 52.7%-75.1%) per blinded independent central review (BICR), meeting the primary end point of the research. Moreover, the median duration of response (DOR) with the regimen had not yet been reached.

In terms of safety, the most common grade 3 or higher treatment-emergent adverse effects that were experienced by more than 5% of patients included maculopapular rash, anemia, increased lipase, urinary tract infection, hyperglycemia, fatigue, neutropenia, hematuria, diarrhea, acute kidney injury, hyponatremia, chronic kidney disease, decreased weight, syncope, hypophosphatemia, pneumonitis, sepsis, and increased alanine aminotransferase.

Findings were noted to be consistent with what was previously reported in the dose-escalation cohort and expansion cohort A of the trial. Additional data from cohort K of the trial will be shared at an upcoming medical meeting, according to Seagen Inc. and Astellas Pharma Inc.

“We are encouraged by the positive topline results of cohort K for the combination of enfortumab vedotin and pembrolizumab in first-line locally advanced or metastatic urothelial cancer, and we look forward to sharing results at an upcoming medical meeting,” Roger Dansey, MD, interim chief executive officer and chief medical officer of Seagen, stated in a press release.

The multicohort, open-label, multicenter, phase 1/2 trial is examining the safety, tolerability, and efficacy of enfortumab vedotin monotherapy or in combination with pembrolizumab and/or chemotherapy in the first- or second-line settings in patients with locally advanced or metastatic urothelial cancer and in those with muscle-invasive bladder cancer.

Cohort K of the trial enrolled adult patients with unresectable, locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-based chemotherapy and who have not received prior treatment for their disease.

These patients received either enfortumab vedotin alone (n = 73) or in combination with pembrolizumab (n = 76). The key outcome measures of cohort K include ORR per BICR using RECIST v1.1 criteria, and safety.

Enrollment to cohort K of the trial was completed in October 2021.²

“We intend to discuss cohort K results with regulatory authorities as we seek to develop a new first-line treatment combination for these patients,” Ahsan Arozullah, MD, MPH, senior vice president and head of Development Therapeutic Areas at Astellas, stated in a press release.

The combination of the antibody-drug conjugate and the immunotherapy are being examined as part of an extensive collaborative effort, which includes the following phase 3 studies: EV-302/KEYNOTE-A39 (NCT04223856), EV-304/KEYNOTE-B15 (NCT04700124), and EV-303/KEYNOTE-905 (NCT03924895).

In February 2020, the FDA granted a breakthrough therapy designation to enfortumab vedotin plus pembrolizumab in the first-line treatment of patients with unresectable, locally advanced or metastatic urothelial cancer who are not able to receive cisplatin-based chemotherapy.³ The designation was supported by findings from the dose-escalation cohort, and the expansion cohort A of the trial, which showed that the doublet elicited an ORR of 73% in this population.⁴

References

1. Seagen and Astellas announces positive topline results for Padcev (enfortumab vedotin-ejfv) with Keytruda (pembrolizumab) as first-line treatment for advanced urothelial cancer. News release. Seagen, Inc. and Astellas Pharma, Inc. July 26, 2022. Accessed July 26, 2022. https://bit.ly/3cMZlRO
2. Astellas and Seagen complete enrollment in EV-103 trial cohort K combining Padcev (enfortumab vedotin-ejfv) with pembrolizumab as first-line treatment for advanced urothelial cancer. News release. October 12, 2021. Accessed July 26, 2022. https://bit.ly/3owTGlb
3. Astellas and Seattle Genetics receive FDA breakthrough therapy designation for Padcev (enfortumab vedotin-ejfv) in combination with pembrolizumab in first-Line advanced bladder cancer. News release. Astellas Pharma Inc. and Seattle Genetics, Inc. February 19, 2020. Accessed July 26, 2022. https://prn.to/2SXzEQJ
4. Rosenberg JE, Flaig TW, Friedlander TW, et al. Study EV-103: preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. J Clin Oncol. 2020;38(suppl 6):441. doi:10.1200/JCO.2020.38.6_suppl.441