LBA73 - Study EV-103 Cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC)

Background

There is a critical need for effective and tolerable 1L treatment options in la/mUC. Both EV and P have independently shown an OS benefit in previously treated la/mUC. EV preclinical studies have shown hallmarks of immune cell death potentially augmented by PD-1/PD-L1 inhibitors. Results from a previous cohort formed the rationale for this randomized Cohort K.

Methods

Previously untreated cisplatin-ineligible pts with la/mUC were randomized 1:1 to EV (1.25 mg/kg) as monotherapy on Days 1 and 8 or in combination with P (200 mg) on Day 1 of 3-week cycles (EV-103, NCT03288545). The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by BICR. Secondary endpoints included duration of response (DOR) and safety (treatment-related adverse events, TRAEs). There were no formal statistical comparisons between treatment arms.

Results

149 pts were treated: EV+P n=76; EV n=73. Confirmed ORR (95%CI) for EV+P, 64.5% (52.7, 75.1), median DOR was not reached. Confirmed ORR (95%CI) for EV, 45.2% (33.5, 57.3) and median DOR (95%CI) 13.2 mos (6.1, 16.0). TRAEs of special interest included skin reactions (EV+P, n=51 [67.1%]; EV, n=33 [45.2%]), peripheral neuropathy (EV+P, n=46 [60.5%]; EV, n=40 [54.8%]), ocular disorders (eg, dry eye and blurred vision; EV+P, n=20 [26.3%]; EV, n=21 [28.8%]), and hyperglycemia (EV+P, n=11 [14.5%]; EV, n=8 [11.0%]). The majority of treatment-related AESIs were Grade ≤2. Table: 000LBA73

Data cutoff: June 10, 2022; +Pts remain on treatment.

Conclusions

EV+P showed high ORR with rapid responses and median DOR not reached in a 1L cisplatin-ineligible population. The safety profile was tolerable and generally consistent with the known profile for EV+P. EV monotherapy was consistent with prior experience. These data support ongoing investigations of 1L EV+P in patients with la/mUC who have a high unmet need.

Clinical trial identification

NCT03288545.

Editorial acknowledgement

Holly Tomlin, MPH, Ray Liao, and Nancy Chang (employees and stockholders, Seagen Inc.) provided writing and editorial assistance.

Legal entity responsible for the study

Seagen Inc., Astellas Pharma, and Merck & Co., Inc.

Funding

Seagen Inc., Astellas Pharma, Merck & Co., Inc.

Disclosure

J.E. Rosenberg: Financial Interests, Personal, Advisory Board: Seagen, Astellas, AstraZeneca, EMD-Serono, Mirati, Tyra Biosciences, Alligator Biosciences, Gilead, QED Therapeutics, Boehringer Ingelheim, Genentech, Pfizer, Infinity Pharmaceuticals, BMS, Janssen, Merck, Lilly Oncology, NCCN; Financial Interests, Personal, Invited Speaker: EMD-Serono; Financial Interests, Personal, Invited Speaker, Medical education: Research to Practice, Physicians Education Resource, MJH Associates; Financial Interests, Personal, Invited Speaker, Medical Education: Clinical Care Options; Financial Interests, Personal, Royalties: Wolters Kluyer/Uptodate; Financial Interests, Institutional, Invited Speaker, Coordinating PI of rogaratinib/atezolizumab trial; consultant, trial open at my institution: Bayer; Financial Interests, Personal and Institutional, Invited Speaker, EV-201, EV- 103; consultant, trial open at my institution: Seagen; Financial Interests, Personal and Institutional, Invited Speaker, EV-301, consultant, trial open at my institution: Astellas; Financial Interests, Institutional, Invited Speaker, Consultant, PI of trial, trial open at my institution: AstraZeneca; Financial Interests, Institutional, Invited Speaker, PI of IMVIGOR210 (still open at my institution): Genentech; Financial Interests, Institutional, Invited Speaker, Investigator initiated trial at my institution: QED; Non-Financial Interests, Leadership Role, Bladder Cadre leader for Alliance (NCTN): Alliance for Clinical Trials in Oncology. M. Milowsky: Financial Interests, Personal, Advisory Board: Loxo/Lilly; Financial Interests, Personal, Other, Co-Editor-in-Chief, Clinical Genitourinary Cancer: Elsevier; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Stocks/Shares: Pfizer, Merck, Gilead Sciences; Financial Interests, Institutional, Invited Speaker: Merck, Roche/Genentech, Bristol-Myers Squibb, Mirati Therapeutics, Incyte, Seagen, G1 Therapeutics, Alliance Foundation Trials, Alliance for Clinical Trials in Oncology, Clovis Oncology, Arvinas, Regeneron. C. Ramamurthy: Financial Interests, Advisory Board: Seagen; Financial Interests, Speaker’s Bureau: Gilead. N. Mar: Financial Interests, Speaker’s Bureau: Seagen, Astellas Pharma. R.R. McKay: Financial Interests, Advisory Board: Janssen, Novartis, Tempus, Exelixis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion Therapeutics, Calithera Biosciences, AstraZeneca, Myovant Sciences, Caris Life Sciences, Sorrento Therapeutics; Financial Interests, Funding: Pfizer, Bayer, Tempus. T. Friedlander: Financial Interests, Advisory Board: AbbVie, Dendreon, Dava Oncology, EMD Serono, Merck, Astellas Pharma, Foundation Medicine, Basilea; Financial Interests, Project Lead: Med BioGene; Financial Interests, Other, Travel Expenses: AstrtaZeneca/MedImmune, Genentech/Roche, Jounce Therapeutics; Financial Interests, Other, Honoria: EMD Serono, AstraZeneca/MedImmune, Astellas Scientific and Medical Affairs Inc; Financial Interests, Research Grant: Janssen, Seagen, Incyte, Bristol-Myers Squibb, Neon Therapeutics, Roche/Genetech. C. Ferrario: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Merck, Knights Therapeutics; Financial Interests, Institutional, Invited Speaker: Astellas, AstraZeneca, Lilly, Merck, Novartis, Roche - Genetech, Sanofi, Seattle Genetics, Sermonix, Zymeworks; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Bayer; Non-Financial Interests, Advisory Role: AstraZeneca, Knights Therapeutics, Merck. S. Bracarda: Financial Interests, Other, Travel Expenses: Astellas Pharma; Financial Interests, Other: Seagen. S. George: Financial Interests, Personal, Advisory Board, advisor/consultant: BMS, Bayer, pfizer, Exelixis, Corvus, Sanofi/ Genzyme, Seattle Genetics, EMD Serono, Eisai, Merck, Aveo, QED therapeutics; Financial Interests, Institutional, Invited Speaker: Pfizer, Merck, Agensys, Novartis, BMS, Bayer, Eisai, Seattle Genetics, Calithera, Corvus, Surface Oncology, Exelixis, Aravive, Aveo, Gilead. H. Moon: Financial Interests, Funding: Bristol-Myers Squibb, Amgen, Prometheus. D. Geynisman: Financial Interests, Personal, Advisory Board: Pfizer, Merck, Exelixis, Astellas, Genentech; Financial Interests, Institutional, Invited Speaker: Genentech, Merck, Harpoon, Seattle Genetics. D.P. Petrylak: Financial Interests, Advisory Role: Bayer, Exelixis, Pfizer, Roche, Astellas Pharma, AstraZeneca, Lilly, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Incyte, Janssen, Pharmacyclics, Seagen, Urogen pharma, Advanced Accelerator Applications, Ipsen, Bicycle Therapeutics, Mirati Therapeutics, Monopteros Therapeutics, Regeneron, Gilead Sciences; Financial Interests, Expert Testimony: Celgene, sanofi; Financial Interests, Stocks/Shares: Bellicum Pharmaceuticals, Tyme; Financial Interests, Funding: Progenics, Sanofi, Endocyte, Genentech, Merck, Astellas Medivation, Novartis, AstraZeneca, Bayer, Lilly, Innocrin Pharma, MedImmune, Pfizer, Roche, Seagen, clovis Oncology, Bristol-Meyers Squibb, Advanced Accelerator Applications, Agensys, BioXCel Therapeutics, Eisai, Mirati Therapeutics, Replimune, Medivation, Gilead Sciences. D. Borchiellini: Financial Interests, Advisory Role: Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Pfizer, Sanofi, Merck; Financial Interests, Other, Travel Expenses: Bristol-Myers Squibb, Janssen, Pfizer, Roche; Financial Interests, Funding: Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Infinity Pharmaceuticals, Janssen, MSD, Roche. E.F. Burgess: Financial Interests, Advisory Role: Johnson & Johnson; Financial Interests, Speaker’s Bureau: AstraZeneca, Exelixis; Financial Interests, Stocks/Shares: Exelixis, Becton Dickinson, Calithera Biosciences, Gilead Sciences, Medtronic, Macrogenics, Arvinas, Autolus; Financial Interests, Other, Honoraria: Exelixis, Janssen Oncology, Novartis, Pfizer, Merck; Financial Interests, Funding: Pfizer, Astellas Pharma. J.P. Maroto Rey: Financial Interests, Advisory Role: Astellas, Ipsen, Bristol-Myers Squibb. A. Carret: Financial Interests, Personal, Full or part-time Employment, Senior Medical Director in Clinical Development: Seagen; Financial Interests, Personal, Stocks/Shares, Stocks/Shares/ESPP: Seagen; Non-Financial Interests, Member, ASCO: Seagen; Non-Financial Interests, Member, SIOP: Seagen; Non-Financial Interests, Member, Histiocyte Society: Seagen. Y. Yu: Financial Interests, Stocks/Shares: Seagen; Financial Interests, Full or part-time Employment, Employee: Seagen. M.V. Guseva: Financial Interests, Stocks/Shares: Astellas Pharma. B. Homet Moreno: Financial Interests, Institutional, Full or part-time Employment: Merck Employee; Financial Interests, Institutional, Stocks/Shares: Merck. P.H. O'Donnell: Financial Interests, Stocks/Shares: Allergan; Financial Interests, Other, Honoraria: Genetech/Roche, Merck, Astellas Pharma, Seagen, Atheneum Partners, Health Advances, Janssen, Dedham Group, Pfizer, CLD, Axiom Healthcare Strategies, EMD Serono, IntrinsiQ Specialty Solutions, ISMIE; Financial Interests, Funding: Boehringer Ingelheim, Merck, Genentech/Roche, AstraZeneca/MedImmune, Acerta Pharma, Janssen, Seagen, Bristol-Myers Squibb, Astellas Pharma; Financial Interests, Other, Travel Expenses: Seagen, Astellas, Genentech/Roche; Financial Interests, Other: Janssen, Janssen, Nektar, NIH, Dragonfly Therapeutics, G1 THerapeutics.