2365MO - Study EV-103 cohort L: Perioperative treatment w/ enfortumab vedotin (EV) monotherapy in cisplatin (cis)-ineligible patients (pts) w/ muscle invasive bladder cancer (MIBC)

Background

Current SOC for pts w/ MIBC is neoadjuvant cis-based chemotherapy followed by radical cystectomy and pelvic lymph node dissection (RC+PLND). For pts who are cis-ineligible, SOC is RC+PLND alone but adjuvant therapy may be recommended. Due to high rates of recurrence in cis-ineligible pts, an urgent unmet need remains. Neoadjuvant EV showed promising antitumor activity in MIBC (pathological CR [pCR] of 36%, pathological downstaging [pDS] of 50%) in EV-103 Cohort H ( Petrylak 2022 ). Cohort L examines a perioperative approach.

Methods

Cohort L enrolled pts who are cis-ineligible w/ previously untreated MIBC (cT2-T4aN0M0 or cT1-T4aN1M0) who are medically fit for and agree to undergo curative intent RC+PLND within 12 wks. Pts received 3 cycles of neoadjuvant EV (1.25mg/kg) on Days 1 and 8 of each 3-week cycle followed by RC+PLND and then 6 cycles of adjuvant EV (1.25 mg/kg) on Days 1 and 8 of every 3 week cycle starting 8 weeks post-RC. Primary endpoint is pathological CR (pCR) per central pathology review; secondary endpoints include pathological downstaging (pDS) rate per central pathology review, safety and tolerability. Here we present initial results from the neoadjuvant/RC+PLND phase + 30 days post surgery.

Results

52 pts were enrolled. 51 pts were treated w/ EV in the neoadjuvant phase w/ a median of 3 cycles; 42 pts (82.4%) completed RC+PLND. One pt achieved clinical CR and elected not to undergo RC+PLND and was excluded from pCR and pDS analyses; 17/50 (34.0%) pts had a pCR. pDS was seen in 21/50 (42.0%) pts. In the neoadjuvant/RC+PLND phase, of 51 treated pts most common EV-related TEAEs were fatigue (52.9%), rash maculo-papular (31.4%), and nausea (29.4%). 39.2% of pts had an EV-related TEAE ≥ grade 3; 31.4% pf pts had a RC-related TEAE ≥ grade 3. No surgeries were delayed due to EV-related TEAEs. One pt (2.0%) experienced an EV-related death (Stevens-Johnson syndrome) before surgery.

Conclusions

EV continues to show promising activity and was tolerable in cis-ineligible pts w/ MIBC in this ongoing trial. Both the efficacy and safety profiles were consistent with previously reported data from Cohort H. These data support the ongoing phase 3 trials evaluating EV + pembrolizumab in MIBC.

Clinical trial identification

EudraCT 2018-001527-39; Release Date: Amendment 11, 15-Feb-2023.

Editorial acknowledgement

Sarah Canestaro, MS, of Populus Group, Troy, MI, supported by Seagen Inc. for providing medical writing and editorial support.

Legal entity responsible for the study

Astellas Pharma Global Development, Inc.

Funding

Seagen Inc., Bothell, WA, USA and Astellas Pharma, Northbrook, IL.

Disclosure

S. Sridhar: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, BMS, Eisai, EMD Serono, Hoffmann La Roche, Pfizer; Financial Interests, Institutional, Research Grant, Unrestricted Research grant to institution for developing a database: Seagen; Financial Interests, Institutional, Research Grant: Bayer, Janssen. P.H. O'Donnell: Financial Interests, Personal, Other, Honoraria: Merck, Astellas Pharma, Pfizer, CLD, Axiom Healthcare Strategies, EMD Serono, IntrinsiQ Specialty Solutions, ISMIE, NAMCP, Seagen, Curio Science, FirstWord Publications, MedLearning Group, Research to Practice, Great Debates and Updates, MJH Life Sciences, Peerview, Vaniam Group, EnquiringMinds; Financial Interests, Institutional, Funding, Research Funding: Boehringer Ingelheim, Merck, Genentech/Roche, AstraZeneca/MedImmune, Acerta Pharma, Janssen, Seagen, Bristol Myers Squibb, Astellas Pharma; Other, Personal, Expert Testimony: Oregon Health & Science University (OHSU); Other, Personal, Other, Travel, Accommodations, Expenses: Curio Science; Other, Personal, Other Relationship: Janssen, Nektar, NIH, Dragonfly Therapeutics, G1 Therapeutics. T.W. Flaig: Financial Interests, Personal, Other, Consulting and advisory: Seattle Genetics; Financial Interests, Institutional, Member of Board of Directors: Joint Venture between University of Colorado and UCHealth; Financial Interests, Personal, Stocks/Shares, I am founder and stockholder in this academic start up company. We are submitting SBIR grants for a patent on work done in our lab. There are no commercial products or current clinical trials - early stage: Aurora Oncology; Financial Interests, Personal, Other, We have a patent with the University of Colorado (from our lab) which has been licensed to Aurora Oncology (I am a cofounder of this faculty start up): Aurora Oncology; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Janssen Oncology, Sanofi, Pfizer, Roche - Genentech, AstraZeneca/MedImmune, Lilly, Astellas, Seattle Genetics, Seagen, Merck, La Roche - Posay, Myovant Sciences. J.E. Rosenberg: Financial Interests, Personal, Advisory Board: Alligator Biosciences, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, EMD-Serono, Genentech, Gilead, Infinity Pharmaceuticals, Janssen, Lilly Oncology, Merck, Mirati, NCCN, Pfizer, QED Therapeutics, Seagen, Tyra Biosciences, Hengrui; Financial Interests, Personal, Invited Speaker, Medical Education: Clinical Care Options; Financial Interests, Personal, Invited Speaker: EMD-Serono; Financial Interests, Personal, Invited Speaker, Medical education: MJH Associates, Physicians Education Resource, Research to Practice; 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. C.J. Hoimes: Financial Interests, Personal, Advisory Board: Astellas, BMS, Foundation Medicine, Merck &Co, Seagen, Tempus; Financial Interests, Personal, Invited Speaker: BMS, Eisai; Financial Interests, Institutional, Advisory Board: Dynavax; Financial Interests, Institutional, Invited Speaker: AbbVie, Alkermes, Astellas, BMS, Bayer, Bellicum, BioNTech, Dynavax, Genentech, Janssen, Mirati, NeoImmune Tech, Pfizer, Phosplatin, Prometheus; Financial Interests, Personal and Institutional, Invited Speaker: Merck &Co, Seagen. M.I. 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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. R.R. 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Coelho Barata: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Eisai, Exelixis, Janssen, EMD Serono, Dendreon, Pfizer, Seattle Genetics, BMS, Bayer; Financial Interests, Personal, Invited Speaker: Caris Life Sciences, UroToday. C. Hwang: Financial Interests, Personal, Other, Consultant: Tempus; Financial Interests, Personal, Advisory Board: EMD Sorono, Genzyme (Sanofi), Dendreon; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson; Financial Interests, Institutional, Invited Speaker: Merck, Seagen, AstraZeneca, Bayer; Non-Financial Interests, Sponsor/Funding: Henry Ford Health System Government Affairs Services Pac. M. Cruz-Correa: Financial Interests, Institutional, Research Grant: Merck, SeaGen, BMS, Taiho, Pfizer, Janssen, AbbVie, Genentech, Incyte, Huyabio, BeiGene. M. Iafolla: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Bayer, Canadian Urologic Association, Ipsen, Merck, Sanofi, Save Your Skin, Sermo Team; Financial Interests, Personal, Expert Testimony: CompassMD, MD Analytics; Financial Interests, Personal, Full or part-time Employment: William Osler Health System; Financial Interests, Institutional, Research Grant: EMD Serono, Pfizer, Bristol Myers Squibb, Novartis; Non-Financial Interests, Principal Investigator: Seagen, Pfizer, Bristol Myers Squibb, AstraZeneca, Astellas Pharma Global Development Inc. M. 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Moon: Financial Interests, Institutional, Invited Speaker, clinical trial PI: Seagen; Financial Interests, Personal and Institutional, Invited Speaker, Steering Committee: EMD Serono; Financial Interests, Institutional, Invited Speaker, PI for Clinical trial: Janssen; Financial Interests, Institutional, Invited Speaker, PI for Trial: Nektar; Financial Interests, Invited Speaker, Clinical trial PI: Huya; Non-Financial Interests, Other, Grant Proposal Review committee for NCCN/Pfizer Bladder cancer grant review committee: NCCN; Non-Financial Interests, Advisory Role, NCI Prostate Cancer task force: NCI.