Bladder cancer "platinum free, targeted + immune" program! The combination of padcev + keytruda obtained the breakthrough drug qualification, and the total remission rate of first-line treatment was 73.3%

February 21, 2020 / BIOON / -- Seattle genetics and Astellas recently announced that the U.S Food and Drug Administration (FDA) has awarded the antibody drug conjugate (ADC) padcev (enfortumab) The combination of vedotin and keysruda (coreda, common name: pembrolizumab, pabolizumab) is a breakthrough drug qualification (BTD) for the treatment of locally advanced or metastatic urothelial carcinoma (UC) patients who cannot receive cisplatin chemotherapy in the first-line treatment BTD is a new drug review channel established by FDA in 2012 It aims to accelerate the development and review of new drugs for the treatment of serious or life threatening diseases and there is preliminary clinical evidence that the drug can substantially improve the condition compared with existing treatment drugs The drugs that obtain BTD can receive more close guidance, including FDA senior officials, during the research and development, so as to guarantee to provide patients with new treatment options in the shortest time FDA awarded padcev + keytruda combined drug regimen BTD based on the results of the incremental dose cohort and extended cohort a of IB / phase II clinical trial ev-103 (nct03288545) These cohorts assessed whether padcev + keytruda regimens were not suitable for locally advanced or metastatic UC patients receiving cisplatin based chemotherapy regimens in the first-line treatment The latest results have been published at the 2020 urogenital cancer symposium The data showed that the median follow-up time was 11.5 months, and the results of the study continued to meet the safety indicators, and showed that padcev + keytruda, a platinum free combination regimen, achieved encouraging clinical efficacy in the first-line treatment of UC: the confirmed objective response rate (ORR) was 73.3% (n = 33 / 45, 95% CI: 58.1), 85.4); among them, Cr was 15.6% (n = 7 / 45), PR was 57.8% (n = 26 / 45) The median duration of remission (DOR) has not reached (1.2-12.9 months or more) At the time of data analysis, 8 of 33 patients with remission kept remission, 83.9% patients had remission duration ≥ 6 months, 53.7% patients had remission duration ≥ 12 months Median progression free survival (PFS) was 12.3 months (95% CI: 7.98, -) The overall 12-month survival (OS) rate was 81.6% (95% CI: 62-91.8%), and the median OS was not achieved Ev-103 is an ongoing multi cohort, open label, multi center Ib / II clinical trial to evaluate the safety, tolerability and efficacy of padcev + keytruda in the treatment of muscle invasive, locally advanced, first-line and second-line metastatic urothelial carcinoma Recently, Seattle genetics and Tailai have launched the phase EV-302 III trial to investigate the non platinum regimen Padcev+Keytruda in first-line treatment "Cisplatin based chemotherapy is the standard treatment for first-line and advanced urothelial cancer; however, it is not an option for many patients," said Jonathan E Rosenberg, MD, oncologist and director of urogenital oncology services at Memorial slonketlin cancer center in New York The mid-term results of the ev-103 study are very encouraging, including strong data on median PFS for up to a year in the first-line treatment of padcev + keytruda, a platinum free regimen " It is estimated that there will be about 81000 people diagnosed with bladder cancer in the United States by 2020 Urothelial carcinoma (UC) accounts for 90% of all bladder cancers The first-line treatment for patients with advanced UC is cisplatin based chemotherapy For patients who can not receive cisplatin treatment, such as patients with impaired renal function, carboplatin based treatment is recommended However, less than half of the patients responded to the carboplatin regimen and the outcome was generally poor compared to the cisplatin regimen Padcev is a first-in-class antibody drug conjugate (ADC), targeting a cell surface protein highly expressed in bladder cancer The drug is made by coupling the human IgG1 monoclonal antibody enfortumab targeting at the connexin-4 with the cytotoxic agent MMAE (monomethyl auristatin e, a microtubule destroying agent) Nectin-4 is a highly expressed therapeutic target in many solid tumors, including urothelial carcinoma (UC) In the drug, ADC link technology is from Seattle genetics company, and target identification is completed by anstar In December 2019, padcev was approved by the US FDA to treat patients with locally advanced or metastatic urothelial carcinoma (UC), the most common type of bladder cancer, specifically: patients who have previously received a PD-1 / L1 inhibitor treatment and who have received a platinum containing chemotherapy regimen in new adjuvant / adjuvant treatment or in the treatment of locally advanced or metastatic diseases It is worth mentioning that padcev is the first ADC drug approved to treat UC, and also the first drug approved to be used in patients with locally advanced or metastatic UC who have previously received chemotherapy containing platinum and a PD-1 or PD-L1 inhibitor The drug was approved through the FDA's priority review process, three months ahead of schedule Previously, FDA has granted padcev a breakthrough drug qualification to treat the above UC patients Original source: astras and Seattle genetics receive FDA break through therapy design for padcev Gamma (enfortumab vedotin-ejfv) in Combination with Pembrolizumab in First-Line Advanced Bladder Cancer