Padcev Demonstrates Significant Efficacy in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer Patients

News on February 15, 2022 /BioValleyBIOON/ -- Astellas and Seagen recently announced preliminary results from Cohort H of the Phase 1b/2 EV-103 trial. The trial is investigating the antibody-drug conjugate (ADC) Padcev (enfortumab vedotin) as a monotherapy for the treatment of patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy.

MIBC is a stage of bladder cancer, characterized byTumorMarked by diffusion to the bladder wall muscle. The treatment of MIBC typically combines cisplatin-based chemotherapy, radical cystectomy, and pelvic lymph node dissection. Cohort H of the EV-103 trial enrolled MIBC patients who were eligible for surgical treatment but ineligible for cisplatin chemotherapy. In the study, these patients received Padcev as neoadjuvant (preoperative) treatment on days 1 and 8 of each cycle for a total of 3 cycles.

Preliminary analysis results of 22 patients show that,36.4% of patients achieved pathological complete response (pCR)., the primary endpoint of the trial, indicates that microscopic examination of the tissue cells removed during surgery showed no signs of cancer.Half (50%) of all patients experienced a pathological stage reduction, orTumorVolume reduction, which is the secondary endpoint of the trial.All patients underwent surgery without any surgical delays after receiving Padcev treatment.The most common (≥20%) adverse events (AEs) associated with Padcev treatment were fatigue (45.5%), alopecia (36.4%), dysgeusia (36.4%), diarrhea (27.3%), nausea (27.3%), peripheral sensory neuropathy (27.3%), dry eye (22.7%), and maculopapular rash (22.7%), which is consistent with the known safety profile of Padcev.

Neoadjuvant chemotherapy based on cisplatin aims to shrink tumors before surgery to extend the survival of patients with MIBC. However, up to half of these MIBC patients are not eligible for cisplatin treatment and usually have to undergo surgery without cisplatin chemotherapy. The results of Cohort H of the EV-103 trial showed that when patients were treated with Padcev before surgery, more than a third of the patients had residual bladder and microscopic examination after cystectomy.TumorThere were no signs of cancer at the time. All patients underwent surgery after treatment with Padcev. Given the lack of standard neoadjuvant care for patients ineligible for cisplatin chemotherapy, these results are significant and support further research.

Padcev is a first-in-class ADC drug that targets Nectin-4 (a cell surface protein highly expressed in bladder cancer).This drug is composed of enfortumab, a human IgG1 monoclonal antibody targeting Nectin-4, conjugated with the cytotoxic agent MMAE (monomethyl auristatin E, a microtubule disruptor). Nectin-4 is expressed in various solid tumors, including urothelial cancer (UC).TumorModerately to highly expressed therapeutic targets. In this drug, the ADC linker technology comes from Seagen.GeneticsSeagen, Inc., target identification completed by Astellas Pharma, Inc.

In December 2019, Padcev was granted accelerated approval by the U.S. FDA for the treatment of adult patients with locally advanced or metastatic UC, specifically: patients who have previously received a PD-1/L1 inhibitor and have also received a platinum-based chemotherapy regimen either before surgery (neoadjuvant) or after surgery (adjuvant) or in the treatment of locally advanced or metastatic disease. In July 2021, Padcev received regular approval from the FDA and obtainedFDAApproval for expanded indications: For the treatment of adult patients with locally advanced or metastatic UC who are ineligible for cisplatin chemotherapy and have previously received first-line or multiple lines of therapy.

Notably, Padcev is the world's first ADC drug approved for the treatment of UC, and it is also the first drug approved for patients with locally advanced or metastatic UC who have previously received platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.FDAPadcev has been granted Breakthrough Therapy Designation for the treatment of the aforementioned UC patients. (Bioon.com)

Source of the original text:Astellas and Seagen Announce Initial Results of PADCEV (enfortumab vedotin-ejfv) in Patients With Muscle-Invasive Bladder Cancer Not Eligible for Cisplatin Chemotherapy