"Platinum free, targeted + immunotherapy" for bladder cancer! The total remission rate of the new ADC drug padcev combined with keytruda was 73.3%!

February 12, 2020 / BIOON / -- Seattle genetics and Astellas recently released the latest results of IB / phase II clinical trial ev-103 The trial was carried out in 45 patients with locally advanced or metastatic urothelial carcinoma (UC) who had not previously received treatment (initial treatment), and these patients were not suitable for cisplatin based chemotherapy In this study, the safety and efficacy of the combination of antibody drug coupling compound (ADC) padcev (enfortumab vedotin) and mexadone anti PD-1 therapy keytruda (Coretta, common name: pembrolizumab, pabolizumab) were evaluated The results showed that after 11.5 months of median follow-up, the safety indexes were met, and that padcev + keytruda, a platinum free combination drug, achieved encouraging clinical effects in the first-line treatment of UC: the objective response rate (ORR) was 73.3%, and the median progression free survival period (PFS) was 12.3 months 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 Urology and reproductive 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 " The detailed results of the ev-103 study will be presented at the 2020 urogenital cancer symposium on February 14 The specific data were: median follow-up of 11.5 months (range: 0.7-19.2), confirmed objective response rate (ORR) was 73.3% (n = 33 / 45, 95% CI: 58.1, 85.4); among them, complete response rate (CR) was 15.6% (n = 7 / 45), partial response rate (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 In the study, 58% (26 / 45) of patients had ≥ grade 3 treatment-related adverse events: lipase elevation (18%; 8 / 45), rash (13%; 6 / 45), hyperglycemia (13%; 6 / 45) and peripheral neuropathy (4%; 2 / 45); these rates were similar to those of padcev alone 18% (8 / 45) of the patients experienced grade 3 treatment-related immune-mediated adverse events requiring systemic steroids (arthralgia, bullous dermatitis, pneumonia, lipase elevation, erythema, macular papule, tubulointerstitial nephritis, myasthenia gravis) No patients experienced grade 5 adverse events Six patients (13%) stopped treatment due to treatment-related adverse events, the most common one was peripheral sensory neuropathy As mentioned earlier, the researchers believe that one death was related to treatment and attributed to multiple organ dysfunction syndrome 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 Source of original text: Seattle genetics and Atlas announcement updated results from phase 1B / 2 trial of padcev (envision vedotin ejfv) in combination with immune therapy pembrolizumab as investigative first line treatment for advanced blade cancer