Groundbreaking trial data for patients with advanced bladder cancer

Reference: February 2024 | Issue 2 | Vol 10 | Page 48

Astellas Pharma recently announced results from the open-label, randomised controlled phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) for enfortumab vedotin in combination with pembrolizumab versus chemotherapy.

The combination improved overall survival (OS) and progression- free survival (PFS) with statistically significant and clinically meaningful results in patients with previously untreated locally advanced or metastatic urothelial cancer. The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2023 as part of the Presidential Session.

The EV-302 study enrolled 886 patients with previously untreated locally advanced or metastatic urothelial cancer who were eligible for cisplatin- or carboplatin-containing chemotherapy. It met its dual primary endpoints of OS and PFS, compared to platinum and gemcitabine chemotherapy. Patients treated with enfortumab vedotin and pembrolizumab experienced:

• Median OS of 31.5 months compared to 16.1 months in the chemotherapy arm.
• Significantly prolonged OS, reducing the risk of death by 53 per cent compared to treatment with chemotherapy.
• An independent data monitoring committee determined that OS crossed the pre-specified efficacy boundary at interim analysis.
• Median PFS of 12.5 months compared to 6.3 months in the chemotherapy arm.
• A 55 per cent reduction in the risk of cancer progression or death compared to treatment with chemotherapy.
• Consistent OS results across all pre-defined subgroups, including cisplatin eligibility and PD-L1 expression level.

The most common grade 3 or higher adverse events related to treatment with enfortumab vedotin and pembrolizumab were rash maculo-papular, hyperglycaemia, neutropaenia, peripheral sensory neuropathy, diarrhoea, and anaemia. The safety results in EV-302 are consistent with those previously reported with this combination in EV-103 in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer. No new safety issues were identified.

Dr Ahsan Arozullah, Senior Vice-President and Head of Oncology Development at Astellas said: “The remarkable findings presented today demonstrate that the combination of enfortumab vedotin and pembrolizumab could offer longer survival and more time without disease progression for patients with advanced urothelial cancer.

The presentation of this data is an important milestone for this patient population, and we look forward to continued discussions with regulatory authorities as we work to expedite this therapy to those who need it most.”

Among secondary endpoints, results demonstrated a 68 per cent confirmed objective response rate (ORR) in patients treated with enfortumab vedotin plus pembrolizumab, versus an ORR of 44 per cent in patients treated with chemotherapy.

In the enfortumab vedotin plus pembrolizumab group, 29.1 per cent of patients experienced a complete response, and 38.7 per cent of patients experienced a partial response, compared with 12.5 per cent and 32 per cent in the chemotherapy arm, respectively. The median duration of response was not reached in the enfortumab vedotin plus pembrolizumab arm, versus seven months in the chemotherapy arm.

The EV-302 trial is intended to serve as the basis for global submissions and as the confirmatory trial for the US accelerated approval of this combination.

In April 2023, the US Food and Drug Administration granted an accelerated approval to enfortumab vedotin in combination with pembrolizumab for the treatment of adult patients with locally advanced or metastatic urothelial cancer who are not eligible to receive cisplatin-containing chemotherapy based on tumour response rate and durability of response from the EV-103 trial. The EV-302 trial is part of an extensive programme evaluating this combination in multiple stages of urothelial cancer and other solid tumours.

EV-302 Primary Investigator Prof Thomas Powles, Professor of Genitourinary Oncology at Queen Mary University of London and Director at Barts Cancer Centre, London, added: “An advanced urothelial cancer diagnosis is difficult for patients and their families, and physicians have limited treatment options for these patients. The results of this phase 3 trial are unlike any we have seen so far and open a new chapter in advanced urothelial cancer treatment. This presents a great opportunity for this medicine to make a meaningful impact on advanced urothelial cancer patients, who face an urgent need for new therapies.”