1964MO - Alliance A031501: AMBASSADOR study of adjuvant pembrolizumab (Pembro) in muscle-invasive urothelial carcinoma (MIUC) vs observation (Obs): Extended follow-up disease-free survival (DFS) results and metastatic (met) disease recurrence distribution

Background

The AMBASSADOR study (NCT03244384) demonstrated a significant improvement in DFS for adjuvant Pembro vs Obs in patients (pts) with high-risk MIUC after radical surgery. We report extended DFS (19 additional median (m) months (mo)) follow-up data, sites of met recurrence, and lymph node (LN) status outcomes.

Methods

This is an open label, randomized, phase 3 trial that enrolled pts with MIUC of the bladder, upper tract (UT), or urethra. Pts were randomized 1:1 to receive Pembro 200 mg every 3 weeks for 1 year or Obs. The dual primary endpoints were DFS and OS. Final OS analysis requires additional events.

Results

702 pts were randomized. mDFS follow-up was 41.3 mo. DFS benefit was seen in most subgroups analyzed including pathologic stage, +margins, NAC (yes/no), PD-L1 status (+/-), age, and ECOG PS. DFS benefit for UT ureter tumors was observed but not for renal pelvis tumors. DFS benefit with Pembro was seen in all pts with N0 and N+ stage and UT tumors with N+ stage. Common sites of met included LN, pelvic mass, lung, bone, liver (Table, *non-mutually exclusive; NE-Not Estimable). Table: 1964MO

Conclusions

With extended DFS follow-up, Pembro continues to show DFS benefit vs Obs. All pts, including UT pts (trend) had DFS benefit with Pembro regardless of LN status (N0 or N+). Met recurrences were more common in pts on Obs vs Pembro and the sites of distribution were similar.

Clinical trial identification

NCT03244384.

Editorial acknowledgement

Legal entity responsible for the study

Alliance.

Funding

U10CA180821, U10CA180882; U10CA180820; U10CA180888; Merck Sharp & Dohme Corp.

Disclosure

G.P. Sonpavde: Financial Interests, Personal, Advisory Board: EMD Serono, Bristol Myers Squibb, Genentech, Merck, Seattle Genetics, Exelixis, Janssen, Bicycle Therapeutics, Gilead, Scholar Rock, G1 Therapeutics, Loxo Oncology, Lucence, Tempus, Syapse, Astellas, Pfizer, Atkis, Kura, Syncorp, Vial, PrecisCa; Financial Interests, Personal, Advisory Board, Editor of Bladder cancer virtual center of excellence for Practice Update: Elsevier; Financial Interests, Personal, Other, Member of data safety monitoring board: Mereo; Financial Interests, Personal, Other, Author of chapter: Uptodate; Financial Interests, Personal, Invited Speaker: Research to practice, Seattle Genetics, Gilead, Exelixis, Janssen, Astellas, Merck, Aveo, Pfizer, Natera, Bayer, PeerView, Ideology Health, Grand Rounds in Urology, Onviv; Financial Interests, Personal, Advisory Board, to develop a trial in bladder cancer: Servier Pharmaceuticals; Financial Interests, Personal, Advisory Board, Investigational drug development for HER2+ cancers: Daiichi Sankyo/AstraZeneca; Financial Interests, Institutional, Research Grant: Gilead, EMD Serono, Jazz Pharma; Financial Interests, Institutional, Local PI: BMS; Non-Financial Interests, Principal Investigator, Steering committee of trial: Bristol Myers Squibb; Non-Financial Interests, Other, steering committee of trial: Merck; Other, Spouse employment: Myriad Genetics; Other, Travel: BMS, Astellas. S. Berg: Financial Interests, Personal, Advisory Board: Pfizer, Exelixis. W. Kim: Financial Interests, Personal, Advisory Board: Focal Medical, OncoRev, GeneCentric; Financial Interests, Personal, Other, Founder (spouse): Focal Medical; Financial Interests, Personal, Stocks/Shares: AbbVie, Amgen, Apellis, Arvin's, BeiGene, Bristol Myers Squibb, Eli Lilly, Moderna, Novo Nordisk, Revolution Medicine, Tango, Viking Therapeutics; Financial Interests, Personal, Ownership Interest: Focal Medical; Financial Interests, Personal and Institutional, Research Grant: Merck; Other, Have held Natera stock within last 2 years. Do not currently own: Natera. M.Y. Teo: Financial Interests, Personal, Research Funding: Astellas; Financial Interests, Personal, Research Grant: BMS. R.F. Sweis: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, BMS, EMD serono, Exelixis, Eisai, Janssen, Mirati, Pfizer, Seattle Genetics; Financial Interests, Personal, Invited Speaker: Aveo; Financial Interests, Personal, Stocks/Shares: AbbVie; Financial Interests, Institutional, Local PI: AbbVie, Aduro, Ascendis, Astellas, BMS, Bayer, CytomX, Eisai, Genentech/Roche, Immunocore, Merck, Mirati, Moderna, Novartis, QED, Pyxis Oncology, ALX Oncology; Financial Interests, Institutional, Research Grant: Epivax; Financial Interests, Institutional, Steering Committee Member: Gilead. D. Geynisman: Financial Interests, Personal, Advisory Board: Pfizer, Merck, Exelixis, Astellas, Genentech, Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Genentech, Merck, Harpoon, Seattle Genetics, Arvin's. P. Grivas: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Bristol Myers Squibb, Asieris Pharmaceuticals, Merck KGaA, Seattle Genetics, Aadi Bioscience, Pfizer, Janssen, Boston Gene, Genentech/Roche, Gilead Sciences, CG Oncology, ImmunityBio, Lucence Health, G1 Therapeutics, Fresenius Kabi, PureTech, Strata Oncology, Astellas Pharma, AbbVie; Financial Interests, Institutional, Local PI: Pfizer, Gilead Sciences, Bristol Myers Squibb, MSD, QED Therapeutics, GSK, Mirati Therapeutics, G1 Therapeutics, Merck KGaA, Acrivon Therapeutics, ALX Oncology, Genentech. Z. Reichert: Financial Interests, Personal, Advisory Board: Huff Powell Bailey, Astrazeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Cellgene. J.W. Kim: Financial Interests, Institutional, Local PI: Regeneron, Janux, Cosmo, Genentech/Roche, Antengene Biologics Limited, Hummingbird Bioscience, Acrivon Therapeutics, IGM Biosciences, Inc; Financial Interests, Institutional, Research Grant: Dendreon; Financial Interests, Personal, Local PI: AstraZeneca; Non-Financial Interests, Principal Investigator: AstraZeneca, Takeda. M.A. Bilen: Financial Interests, Personal, Advisory Board: Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Nektar, EMD Serono, Seagen, Sanofi; Financial Interests, Institutional, Local PI: Merck, Xencor, Bayer, Bristol Myers Squibb, Genentech/Roche, Seagen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, Pfizer. B.A. McGregor: Financial Interests, Personal, Advisory Board: Exelixis, BMS, Dendreon, Seagen, Astellas, Eisai, Pfizer, Gilead, Arcus, Loxo/Lily; Financial Interests, Personal, Invited Speaker: EMD Serono, Seagen; Financial Interests, Institutional, Trial Chair: Pfizer, Exelixis, Exelixis, BMS, Gilead; Financial Interests, Institutional, Local PI: Calithera, Seagen, Aveo; Non-Financial Interests, Member: ASCO. S. Srinivas: Financial Interests, Personal, Advisory Board: Janssen, Novartis; Financial Interests, Local PI: Seagen; Financial Interests, Institutional, Local PI: Novartis, REGN, Merck. S. Halabi: Financial Interests, Personal, Other, Member of DSMB: Sanofi, Aveo Oncology, BMS, Janssen, CG Oncology; Financial Interests, Institutional, Funding: ASCO; Financial Interests, Institutional, Coordinating PI, co-PI on Funded Research: Astellas. M.J. Morris: Financial Interests, Personal, Advisory Board: Oric, Pfizer, Exelixis, Lantheus, AstraZeneca, Amgen, Daiichi, Convergent, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix, Z-alpha; Financial Interests, Personal, Invited Speaker: Progenics, ITM Isotope Technologies; Financial Interests, Personal, Stocks/Shares: Doximity; Financial Interests, Institutional, Coordinating PI: Novartis, Celgen; Financial Interests, Institutional, Local PI: Corcept, Janssen, Astellas; Non-Financial Interests, Advisory Role: Bayer, Janssen Oncology, Novartis; Other, Travel to conference: AstraZeneca; Other, Travel/lodging at conference: APCCC. J.E. Rosenberg: Financial Interests, Personal, Advisory Board: Aadi Biosciences, Alligator Biosciences, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, EMD-Serono, Genentech, Gilead, IMVax, Janssen, Lilly Oncology, Merck, Mirati, NCCN, Pfizer, Tyra Biosciences, Aktis, Samsung Bioepis, Century Therapeutics, Bayer, Kalivir; Financial Interests, Personal, Invited Speaker, Medical Education: Clinical Care Options, Peer Direct; Financial Interests, Personal, Invited Speaker, Medical education: MJH Associates, Physicians Education Resource, Research to Practice; Financial Interests, Personal, Invited Speaker: Pfizer, Medscape, Mashup Media; Financial Interests, Personal, Advisory Board, + travel funding to attend meeting: Seagen; Financial Interests, Personal, Royalties: Wolters Kluyer/Uptodate; Financial Interests, Institutional, Coordinating PI, Coordinating PI of rogaratinib/atezolizumab trial; consultant: Bayer; Financial Interests, Personal and Institutional, Steering Committee Member, EV-201, EV- 103; consultant, trial open at my institution: Seagen; Financial Interests, Personal and Institutional, Steering Committee Member, EV-301, consultant, trial open at my institution: Astellas; Financial Interests, Personal and Institutional, Coordinating PI, Consultant, PI of trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, PI of IMVIGOR210 (still open at my institution): Genentech; Financial Interests, Institutional, Coordinating PI, PI of trial, consultant to company: Loxo Oncology; Non-Financial Interests, Leadership Role, Genitourinary Committee Chair: Alliance for Clinical Trials in Oncology. All other authors have declared no conflicts of interest.