Bladder Cancer : ASCO 2021

With ASCO 2021 here, DelveInsight’s consultants are analyzing breakthroughs in Bladder Cancer presented at ASCO21, penning down thoughts on the impact on the market. Here are some of the key abstracts covered from the space. 

Abstract# 4524: Astella’s Antibody Drug Conjugate (ADC), Enfortumab vedotin ready for label expansion through EV-201 Study

In December 2019, Enfortumab vedotin-ejfv (PADCEV; Astellas), a first-in-class Antibody–Drug Conjugate (ADC) directed against Nectin-4, received a green light from the US FDA based on the results from phase III EV-201 study (cohort 1), which evaluated the drug as a monotherapy for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/m UC) who had previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and platinum-containing chemotherapy in the neo-adjuvant/adjuvant, locally advanced or metastatic setting.

The company now seeks to expand the label expansion for the drug by investigating it in cohort 2, which is currently evaluating it in cisplatin-ineligible patients with prior anti-PD-1/L1 treatment and no prior platinum for la/mUC. The cisplatin ineligible status of the patients was due to impaired renal function with the creatinine clearance of ≥30 and <60 ml/min.

The company had already published data from this cohort at ASCO GU 2021, which was held earlier this year and presented an updated analysis from the cohort with three months of follow-up. In this cohort, overall, 91 patients were enrolled between October 2017, and February 2020 and the patients received 1.25 mg/kg of the drug on Days 1, 8, and 15 of each 28-day cycle. The primary endpoint was confirmed objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR). The median age of the patients was 75 years, with more than 70% of patients having the visceral disease.

The data readout revealed that the patients in the study showed a confirmed overall response rate (ORR) of 51% as per blinded independent central review (BICR), including 22% complete response (CR) among the treated patients. The median duration of response (mDOR) was 13.8 months with median progression-free survival (mPFS) and median overall survival (mOS) of 6.7 months and 16.1 months, respectively. The main highlight of the study was the progressive disease in which only 10% of the patients showed progression, and more than 90% of the patients showed clinical benefit. The responses seen in the patients were independent of their subgroup analysis, such as the primary location of the tumour and the presence of liver metastases.

As far as the safety of the drug was concerned, the drug showed no new safety signals and was consistent with the prior studies. All-grade and grade (G) ≥3 treatment-related adverse events (TRAEs) were reported in 97%, and 55% of patients, respectively and 16% of the patients discontinued the treatment due to TRAEs.


Since there is a huge medical unmet need for the patients who progress after immune checkpoint inhibitors and are cisplatin in-eligible, this drug could help patients show better response rates with lower rates of progression during the treatment. Seeing these promising results, the company has requested the US FDA for an expansion of the current label to include patients with la/m UC who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin. The company has also recently submitted a BLA to convert PADCEV’s accelerated approval to regular approval from EV-201 (cohort 1). The submission for this study is based on the phase III EV-301 confirmatory trial.

Abstract #4528: Will Enfortumab vedotin and Keytruda duo head for approval in first-line metastatic urothelial carcinoma (la/mUC)?

Advances for urothelial cancer has shown slow progress, especially for the cisplatin-ineligible patients with metastatic disease, even with the approval of PD-1 monotherapies, which highlights a significant clinical unmet need in the area. The patients with the disease generally show a poor prognosis with lower survival benefits.

Seeing this unmet need, back in late 2019, Seattle Genetics and Astellas Pharma announced a clinical collaboration agreement with Merck to evaluate the combination of Seattle Genetics’ and Astellas’ antibody-drug conjugate (ADC) enfortumab vedotin and Merck’s anti-PD-1 therapy, Keytruda (pembrolizumab), in patients with previously untreated metastatic urothelial cancer. The trio initiated a phase III study to validate the response rates with the combination in the patients with urothelial carcinoma (EV-103). This multi-cohort EV-103 study (NCT03288545) evaluates the safety/activity of enfortumab vedotin and pembrolizumab. (Dose Escalation/Cohort A). The initial results of this study were presented previously and showed remarkable activity, with an overall response rate of 73.3% and a manageable safety profile.

At ASCO 2021, the company presented the updated results with 24.9 months of median follow-up from Cohort A, which investigated the combination for the front-line UC patients. The cohort enrolled 45 patients, including almost 20% of patients who were ECOG performance status 2, as well as 84.4% of patients who had visceral metastases.

The results from the study showed that 93% of the patients showed tumour reduction with the median duration of response (mDOR) of 25.6 months which was not highly expected during the course of the study. The efficacy of the duo was also surprising in terms of median PFS and median OS, which came out to be 12.3 months and 26.1 months, respectively, for a cisplatin-ineligible metastatic urothelial cancer population. In terms of safety, the tolerability and safety profile was similar to what had been previously presented at ASCO GU 2020, with no new safety signals being identified. The patients with liver metastases showed an ORR of 57.1%.


The duo showed remarkable anti-tumour activity in the patients where there is a high unmet need and can prove to be one of the highly utilized combos among oncologists if approved. Moreover, in February 2020, the combo was granted Breakthrough Therapy designation for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting. The company also stated that the combo could potentially support registration under accelerated approval regulations in the United States. In addition to EV-103, the recently initiated EV-302 phase III randomized clinical trial is intended to support global registrations and potentially serve as a confirmatory trial if accelerated approval is granted based on EV-103.

Insightful, wasn’t it? We are covering more from the ASCO21 here.