dm+d

Unassigned

New Medicines

PadcevLocally advanced or metastatic urothelial cancer - third-line in patients previously treated with a PD-1/L1 inhibitor and a platinum-containing chemotherapy

Information

Padcev
New molecular entity
Astellas
Astellas and Seattle Genetics

Development and Regulatory status

None
Pre-registration (Filed)
Launched
Jul 21US approval converted from accelerated to regular approval [17]
Apr 21FDA grants priority review for enfortumab vedotin as part of the Real Time Oncology Review (RTOR) pilot program to convert accelerated approval granted in Dec 19 to regular approval [16]
Mar 21EMA accept MAA for accelerated assessment [15].
Sep 20Results of EV-301 will be submitted to US FDA as the confirmatory trial following accelerated approval in 2019. EV-301 is also intended to support global registrations [13].
Dec 19Launched in the US where a full course of Padcev will cost between $110,000 and $120,000 depending on patient´s weight and treatment duration [12].
Dec 19Continued FDA approval of Padcev may depend on confirmatory trials. The companies expect that an ongoing PIII confirmatory trial will support global registrations [10].
Dec 19Approved in US via accelerated approval process, based on tumour response rate; continued licensing may be conditional on confirmation of clinical benefit [9].
Jul 19Filed in US [8].
Apr 19Astellas is preparing to file enfortumab in urothelial cancer based on positive PII data [5
Sep 18PIII in US & EU [3].
Sep 18Granted breakthrough therapy status in US [4].

Category

Monoclonal antibody-drug conjugate (ADC). The ADC is composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE.
Overall incidence of bladder cancer in the UK is 11.4 per 100,000 population. In developed countries 90% of bladder cancers are transitional cell carcinomas (urothelial cancer); squamous cell carcinomas make up most of the remainder [1].
Locally advanced or metastatic urothelial cancer - third-line in patients previously treated with a PD-1/L1 inhibitor and a platinum-containing chemotherapy
Intravenous infusion

Further information

Yes

Trial or other data

Feb 21PIII RCT (NCT03474107) found enfortumab vedotin significantly prolonged survival vs standard chemotherapy in pts who had previously received platinum-based treatment and a PD-1 or PD-L1 inhibitor (n=608; median follow up 11.1 months; 12.88 vs 8.97 months; HR, 0.70; P=0.001) [14].
Sep 20PIII EV-301 trial is stopped early due to positive results at planned interim analysis (30% reduction in risk of death vs. chemotherapy; HR 0.70; 95% CI[0.56-0.89]; p=0.001) [13].
Dec 19PIII EV-301 study (NCT03474107) is recruiting; collection of primary outcome data still expected to complete Sep 21 [11].
Jun 19PII data (n=125) in patients with urothelial cancer that has locally spread or metastasised has shown that 44% of tumours shrink and 12% of tumours are eliminated on treatment with this drug. Overall survival is extended by 7.6 months, and progression free survival is increased by 6 months [7].
Apr 19PII EV-201 trial found a 44 percent objective response rate (ORR) in patients with locally advanced or metastatic urothelial cancer who have received previous treatment with both platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor [6].
Jun 18PIII EV-301 trial to evaluate overall survival of previously treated patients with locally advanced or metastatic urothelial cancer, following treatment with enfortumab vedotin starts (NCT03474107). 550 adults will be recruited in the US. Primary outcome is overall survival; collection of these data is due to complete Sep 21 [2].

PadcevLocally advanced or metastatic urothelial cancer - second-line or greater in patients ineligible for cisplatin

Information

Padcev
Licence extension/variation
Astellas
Astellas and Seattle Genetics

Development and Regulatory status

None
Phase II Clinical Trials
Launched
Jul 21FDA approves enfortumab vedotin for adult patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy [3]
Apr 21FDA grants priority review for the Supplemental Biologics Licence Application filed in the US based on the pivotal trial EV-201, requesting expansion of the current indication to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and are ineligible for cisplatin [1]

Category

Monoclonal antibody-drug conjugate (ADC). The ADC is composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE.
Overall incidence of bladder cancer in the UK is 11.4 per 100,000 population. In developed countries 90% of bladder cancers are transitional cell carcinomas (urothelial cancer); squamous cell carcinomas make up most of the remainder.
Locally advanced or metastatic urothelial cancer - second-line or greater in patients ineligible for cisplatin
Intravenous infusion

Trial or other data

Feb 21Efficacy and safety results from cohort 2 of the PII EV-201 trial (NCT03219333) were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU). Cohort 2 of the EV-201 trial evaluated Padcev in patients with locally advanced or metastatic urothelial cancer who had been previously treated with a PD-1/L1 inhibitor, had not received a platinum-containing chemotherapy in this setting, and were ineligible for cisplatin. In the trial, 52% of patients who received Padcev had an objective response (95%CI: 40.8, 62.4) and the median duration of response was 10.9 months (95%CI: 5.8, NR). 20% of patients had a complete response, the absence of detectable cancer, and 31% had a partial response. Adverse events were consistent with those observed in previous trial data [2].

Padcev Locally advanced or metastatic urothelial cancer - first-line in combination with pembrolizumab

Information

Padcev
Licence extension / variation
Astellas
Astellas and Seattle-Genetics

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Monoclonal antibody-drug conjugate (ADC). The ADC is composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE.
Urothelial cancer is the most common type of bladder cancer (90 percent of cases). Globally, approximately 549,000 people were diagnosed with bladder cancer last year, and there were approximately 200,000 deaths worldwide [1].
Locally advanced or metastatic urothelial cancer - first-line in combination with pembrolizumab
Intravenous infusion

Padcev Muscle-invasive bladder cancer - perioperative in combination with pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) in cisplatin-eligible patients

Information

Padcev
Licence extension / variation
Astellas
Astellas and Seattle-Genetics

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Monoclonal antibody-drug conjugate (ADC). The ADC is composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE.
There are around 10,200 new bladder cancer cases in the UK every year. It is the 10th most common cancer in the UK. In non-muscle invasive (also called superficial or early) bladder cancer, the cancer cells are only in the inner lining of the bladder. Carcinoma in situ means very early, high grade cancer cells that are only in the innermost layer of the bladder lining. Early bladder cancer may be diagnosed as low, medium or high risk [1].
Muscle-invasive bladder cancer - perioperative in combination with pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) in cisplatin-eligible patients
Intravenous infusion