Pfizer and Astella’s Padcev (enfortumab vedotin) and MSD’s Keytruda (pembrolizumab) administered perioperatively extended survival in certain patients with muscle-invasive bladder cancer (MIBC).
The Phase III EV-303/KEYNOTE-905 trial (NCT03924895) showed both clinically and statistically significant improvement in event-free survival (EFS), the study’s primary endpoint, and overall survival (OS), a key secondary endpoint, with the combination used before and after surgery versus surgery alone.
An additional secondary endpoint of pathologic complete response (pCR) rate was also met.
The combination is being investigated as a neoadjuvant and adjuvant treatment (before and after surgery) in MIBC patients who are not eligible for or declined cisplatin-based chemotherapy, with Dr Moitreyee Chatterjee-Kishore, head of oncology development at Astellas, claiming the Phase III success to be a “breakthrough”.
Chatterjee-Kishore said: “These results from EV-303 represent a breakthrough for cisplatin-ineligible patients with muscle-invasive bladder cancer, demonstrating the potential of Padcev in combination with Keytruda when used before and after surgery as a new standard of care.”
Standard of care (SoC) for MIBC patients is neoadjuvant cisplatin-based chemotherapy followed by surgery. Only around 50% of patients are eligible for this, as half cannot tolerate cisplatin, so they typically undergo surgery without any pharmacological interventions.
The companies claim the combination to be the first and only regimen to improve survival when used before and after surgical cystectomy in cisplatin-ineligible patients with MIBC.
The ongoing trial will continue to evaluate the secondary EFS, OS and pCR endpoints for neoadjuvant and adjuvant Keytruda versus surgery alone.
Pfizer added Padcev, an antibody-drug conjugate (ADC), to its portfolio through a $43bn acquisition of Seagen in 2023, but the medicine is sold as part of a partnership with Astellas.
Pfizer and Astellas hope to broaden Padcev’s use
While Keytruda, a PD-L1 inhibitor, holds approvals in dozens of oncology indications, Padcev has received three approvals from the US Food and Drug Administration (FDA) to date.
It was first granted accelerated approval by the FDA in December 2019 for use in locally advanced or metastatic urothelial cancer for patients who had already received platinum-based chemotherapy and an immune checkpoint inhibitor.
In April 2023, it was granted accelerated approval for use in combination with Keytruda in patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. In December 2023, the combination gained full approval for the first-line treatment of adult patients with locally advanced or metastatic urothelial cancer.
While EV-303/KEYNOTE-905 sets Pfizer and Astellas up for submission of the combo as a neoadjuvant and adjuvant therapy in MIBC, the Phase III EV-304/KEYNOTE-B15 trial (NCT04700124), sponsored by MSD, which is investigating the same combination as a neoadjuvant and adjuvant treatment with surgery in cisplatin-eligible MIBC patients, will also be used in the submission.
GlobalData predicts sales of Padcev to grow from a forecast of $2.61bn in 2025 to $6.3bn in 2031. This sales jump will be bolstered by potential approvals in other indications, including prostate cancer.
GlobalData is the parent company of Clinical Trials Arena.
