During the upcoming 2024 annual meeting of the American Society of Clinical Oncology (ASCO) Annual Meeting, been held from May 31st – June 4th, Astellas Pharma will share new research from across its innovative portfolio of approved and investigational cancer therapies.

A total of 11 abstracts focusing on enfortumab vedotin (Padcev®; Astellas/Pfizer) will be presented, including new data from pivotal trials supporting ongoing regulatory reviews. The data to be presented is expected to reinforce the company’s commitment to changing the course of cancer treatment through targeted therapies for hard-to-treat cancers.

“The data at ASCO demonstrate the strength and breadth of our growing oncology portfolio and provide new insights into our transformative therapies for patients living with some of the most devastating cancers,” noted Tadaaki Taniguchi, MD, PhD, Chief Medical Officer, Astellas

“Recent regulatory achievements mean our oncology medicines are reaching more patients than ever worldwide, and we are continuing to pursue novel targets and invest in research to improve overall survival and raise quality of life,” Taniguchi added.

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What to expect
During the 2024 ASO meeting, expect further data from the Phase 3 EV-302/KN-A39 trial (NCT04223856) evaluating enfortumab vedotin in combination with pembrolizumab (Keytruda®, Merck/MSD) versus chemotherapy (gemcitabine with either cisplatin or carboplatin) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC), including data in cisplatin-eligible and cisplatin-ineligible populations.

These results support the combination as a landmark advancement in the care of patients with la/mUC, regardless of cisplatin eligibility, and serve as the basis of ongoing regulatory reviews by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP), Japan’s Ministry of Health, Labour and Welfare (MHLW), and the China National Medical Products Administration (NMPA).

The U.S Food and Drug Administration (FDA) previously granted accelerated approval to this combination for patients with la/mUC who are ineligible for cisplatin-containing chemotherapy treatment.

Efficacy
As part of the regulatory approval, efficacy was evaluated in EV-302/KN-A39, an open-label, randomized trial of 886 patients with la/mUC and no prior systemic therapy for advanced disease. In this trial, patients were randomized 1:1 to receive either enfortumab vedotin with pembrolizumab or platinum-based chemotherapy. Randomization was stratified by cisplatin eligibility, PD-L1 expression, and presence of liver metastases.

The major efficacy outcome measures were overall survival (OS) and progression-free survival (PFS) as assessed by blinded independent central review.

Statistically significant improvements in both OS and PFS were demonstrated for the combintion enfortumab vedotin with pembrolizumab compared with platinum-based chemotherapy.  Median OS was 31.5 months (95% CI: 25.4, not estimable) for patients who received enfortumab vedotin with pembrolizumab and 16.1 months (95% CI: 13.9, 18.3) for those who received platinum-based chemotherapy (Hazard ratio [HR] 0.47 [95% CI: 0.38, 0.58]; p-value<0.0001). Median PFS was 12.5 months (95% CI: 10.4, 16.6) for patients who received enfortumab vedotin-ejfv with pembrolizumab and 6.3 months (95% CI: 6.2, 6.5) for those who received platinum-based chemotherapy (HR 0.45 [95% CI: 0.38, 0.54]; p-value<0.0001).

The most common (≥20%) adverse reactions, including laboratory abnormalities, in patients receiving enfortumab vedotin with pembrolizumab were increased aspartate aminotransferase, increased creatinine, rash, increased glucose, peripheral neuropathy, increased lipase, decreased lymphocytes, increased alanine aminotransferase, decreased hemoglobin, fatigue, decreased sodium, decreased phosphate, decreased albumin, pruritus, diarrhea, alopecia, decreased weight, decreased appetite, increased urate, decreased neutrophils, decreased potassium, dry eye, nausea, constipation, increased potassium, dysgeusia, urinary tract infection, and decreased platelets.

ASCO presentations

Presentation Lead AuthorWhen presented
Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancerD. PetrylakType: Oral Presentation
Abstract:
Date: June 3,
Time: 8:00-11:00 AM/CDT
Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC)S. GuptaType: Oral Presentation
Abstract: 4502
Date: June 3, 2024
Time: 8:00-11:00 AM / CDT
Enfortumab vedotin (EV) in triple-negative breast cancer (TNBC) and HR+/HER2-breast cancer (BC) cohorts of EV-202A. GiordanoType: Oral Presentation
Abstract: 1005
Date: June 1, 2024
Time: 3:00-6:00 PM / CDT
Enfortumab vedotin (EV) with pembrolizumab (P) versus chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): Analysis of cisplatin (cis)-eligible population from EV-302/KEYNOTE-A39J. BedkeType: Poster Presentation
Abstract: 4562
Date: June 2, 2024
Time: 9:00 AM-12:00 PM CDT
Enfortumab vedotin (EV) with pembrolizumab (P) versus chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): Analysis of the cisplatin (cis)-ineligible population from EV-302/KEYNOTE-A39M. Van Der HeijdenType: Poster Presentation
Abstract: 4563
Date: June 2, 2024
Time: 9:00 AM-12:00 PM CDT
Enfortumab vedotin (EV) in non-squamous and squamous non–small cell lung cancer (NSCLC) cohorts of EV-202K. MuroType: Poster Presentation
Abstract: 8585
Date: June 3,2024
Time: 1:30-4:30 PM/CDT
Enfortumab vedotin (EV) in previously treated gastric/esophageal cancers cohorts of EV-202K. MuroType: Poster Presentation
Abstract: 4046
Date: June 1, 2024
Time: 1:30-4:30 PM/CDT
Study EV-103: Neoadjuvant treatment with enfortumab vedotin monotherapy in cisplatin-ineligible patients with muscle invasive bladder cancer (MIBC): 2-year event-free survival and safety data for Cohort HP. O’DonnellType: Poster Presentation
Abstract: 4564
Date: June 2, 2024
Time: 9:00 AM-12:00 PM/CDT
Enfortumab vedotin and pembrolizumab as first-line treatment in recurrent or metastatic head and neck squamous cell carcinoma: a cohort of the EV-202 trialP. SwiecickiType: Poster Presentation
Abstract: TPS6116
Date: June 2, 2024
Time: 9:00 AM-12:00 PM CDT
Systematic Literature Review and Network Meta-Analysis of First-Line Therapies for Locally Advanced/Metastatic Urothelial CarcinomaL. BloudekType: Online publication
Abstract: e16547
Real-world first-line treatment patterns and outcomes in patients with locally advanced or metastatic urothelial carcinoma in the United StatesR. ChenType: Online Publication
Abstract: e23287

 

Recommend dose
The recommended enfortumab vedotin dose when given with pembrolizumab is 1.25 mg/kg (up to a maximum of 125 mg for patients ≥ 100 kg) administered as an intravenous infusion over 30 minutes on Days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity.

The recommended pembrolizumab dose when given with enfortumab vedotin is 200 mg administered as an intravenous infusion every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or two years of therapy.

Clinical trials
Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer (EV-302)
– ClinicalTrials.gov ID NCT04223856

Highlights of prescribing information
Enfortumab vedotin (Padcev®; Astellas/Pfizer) [Prescribing Information]
Pembrolizumab (Keytruda®, Merck/MSD)[Prescribing Information]

Reference
[1] Hoimes CJ, Flaig TW, Milowsky MI, Friedlander TW, Bilen MA, Gupta S, Srinivas S, Merchan JR, McKay RR, Petrylak DP, Sasse C, Moreno BH, Yu Y, Carret AS, Rosenberg JE. Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. J Clin Oncol. 2023 Jan 1;41(1):22-31. doi: 10.1200/JCO.22.01643. Epub 2022 Aug 30. PMID: 36041086; PMCID: PMC10476837.
[2] Powles T, Valderrama BP, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, Iyer G, Vulsteke C, Park SH, Shin SJ, Castellano D, Fornarini G, Li JR, Gümüş M, Mar N, Loriot Y, Fléchon A, Duran I, Drakaki A, Narayanan S, Yu X, Gorla S, Homet Moreno B, van der Heijden MS; EV-302 Trial Investigators. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024 Mar 7;390(10):875-888. doi: 10.1056/NEJMoa2312117. PMID: 38446675.

Featured image: Astellas Pharma. Exhibition booth during the 2019 annual meeting of the American Society of Medical Oncology (ASCO). Photo courtesy: © 2019 – 2024 Sunvalley Communication. Used with permission

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