Abstract 716TiP
Background
MIBC has few adjuvant treatment (tx) options. ctDNA analysis is a promising approach for selecting pts potentially suitable for checkpoint inhibitors. In IMvigor010, ctDNA positivity identified pts with high-risk muscle-invasive urothelial cancer who may derive disease-free and overall survival (DFS/OS) benefit from adjuvant atezo. ctDNA– pts had a low relapse risk without improved outcomes with atezo vs observation, suggesting they may be spared adjuvant tx (Powles ESMO IO 2020). Following on these data, IMvigor011 is studying adjuvant atezo vs pbo in pts with high-risk MIBC who are ctDNA+ post cystectomy.
Trial design
≈495 pts with histologically confirmed MIBC will be enrolled 6-14 w post cystectomy and must have had lymph node dissection and tumour sample for PD-L1 testing (VENTANA SP142 IHC assay) and whole exome sequencing (WES). Evaluable WES data for development of a personalised mPCR ctDNA assay from post-surgical blood samples (Signatera assay) are required. Adjuvant chemotherapy (AC) or postsurgical radiation are not allowed. Pts given neoadjuvant chemotherapy (NAC) must have ypT2−4a or ypN+ and M0 tumours. Pts not given NAC must be ineligible for or decline AC with cisplatin and have pT3−4a or pN+ and M0 tumours. Pts meeting these criteria will enter a surveillance phase for plasma ctDNA testing (q6w up to 36 w; q12w up to 21 mo). At the first ctDNA+ sample (≥2 mutations), pts with ECOG PS ≤2 and no radiographic recurrence may start a tx phase with 2:1 randomisation to atezo or pbo 1680 mg IV q4w for 12 cycles or up to 1 y or until recurrence (assessed q9w in y 1-2; less often up to y 6) or toxicity. Stratification factors are nodal status, tumour stage post resection, PD-L1 status and time from cystectomy to first ctDNA+ sample. The primary efficacy endpoint (EP) is DFS in pts ctDNA+ ≤20 w post cystectomy (primary analysis population). Key secondary EPs are OS (primary analysis population) and DFS (randomised population; including pts ctDNA+ >20 w post cystectomy). Safety and exploratory predictive, prognostic and pharmacodynamic biomarkers will also be assessed.
Clinical trial identification
NCT04660344.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Bena Lim, PhD, of Health Interactions, Inc., and funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers-Squibb; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Ipsen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Bristol Myers-Squibb; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Johnson & Johnson; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Ipsen. J.E. Gschwend: Financial Interests, Advisory Role: Amgen; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Bayer; Financial Interests, Advisory Role: Janssen-Cilag; Financial Interests, Advisory Role: Merck; Financial Interests, Advisory Role: MSD; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Roche; Financial Interests, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Janssen-Cilag; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb. S. Bracarda: Financial Interests, Advisory Role: Bayer Schering Pharma; Financial Interests, Advisory Role: Bristol-Myers Squibb; Financial Interests, Advisory Role: Ipsen; Financial Interests, Advisory Role: MSD Oncology; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Roche/Genentech; Financial Interests, Other, Travel, Accommodations, Expenses: Astellas Pharma; Financial Interests, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Other, Travel, Accommodations, Expenses: Bristol-Myers Squibb; Financial Interests, Other, Travel, Accommodations, Expenses: Exelixis/Ipsen; Financial Interests, Other, Travel, Accommodations, Expenses: Janssen Oncology; Financial Interests, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Other, Travel, Accommodations, Expenses: Ipsen. D. Castellano: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Astellas; Financial Interests, Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Local PI: Bayer; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Local PI: Clovis; Financial Interests, Institutional, Principal Investigator, Local PI: Eisai; Financial Interests, Institutional, Principal Investigator, Local PI: Exelisis; Financial Interests, Institutional, Principal Investigator, Local PI: GSK; Financial Interests, Institutional, Principal Investigator, Local PI: Ipsen; Financial Interests, Institutional, Principal Investigator, Local PI: Janssen; Financial Interests, Institutional, Principal Investigator, Local PI: Lilly; Financial Interests, Institutional, Principal Investigator, Local PI: MSD; Financial Interests, Institutional, Principal Investigator, Local PI: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: QED Therapeutics; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Non-Financial Interests, Other, Executive member: SOGUG (Spanish Oncology Genito-Urinary Group) Foundation. M. Gross-Goupil: Financial Interests, Personal, Other, Honoraria: Astellas; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria: Astellas; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Advisory Role: Janssen; Financial Interests, Advisory Role: MSD; Financial Interests, Advisory Role: BMS; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Ipsen; Financial Interests, Other, Travel/Accommodation/Expenses: Amgen; Financial Interests, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Other, Travel/Accommodation/Expenses: BMS; Financial Interests, Other, Travel/Accommodation/Expenses: MSD; Financial Interests, Other, Travel/Accommodation/Expenses: Ipsen; Financial Interests, Other, Travel/Accommodation/Expenses: Janssen; Financial Interests, Other, Travel/Accommodation/Expenses: Astellas; Financial Interests, Other, Travel/Accommodation/Expenses: Pfizer. J. Bjerggaard Jensen: Financial Interests, Other, Proctor: Intuitive Surgery; Financial Interests, Advisory Board: Olympus Europe; Financial Interests, Advisory Board: Cephaid; Financial Interests, Advisory Board: Ferring; Financial Interests, Sponsor/Funding. Medac; Financial Interests, Sponsor/Funding. Photocure ASA; Financial Interests, Sponsor/Funding. Cephaid; Financial Interests, Sponsor/Funding. Ferring. A. Kann: Financial Interests, Advisory Role: Janssen; Financial Interests, Advisory Role: Zodiac; Financial Interests, Advisory Role: Pfizer; Financial Interests, Speaker’s Bureau: Janssen. H. Nishiyama: Financial Interests, Advisory Role: Bayer; Financial Interests, Advisory Role: Chugai Pharma; Financial Interests, Advisory Role: Janssen; Financial Interests, Advisory Role: MSD; Financial Interests, Advisory Role: Astellas Pharma; Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Advisory Role: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Ono Pharmaceutical; Financial Interests, Institutional, Funding: Chugai Pharma; Financial Interests, Speaker’s Bureau: Chugai Pharma; Financial Interests, Speaker’s Bureau: MSD; Financial Interests, Speaker’s Bureau: Astellas Pharma; Financial Interests, Speaker’s Bureau: AstraZeneca. L. Makaroff: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Full or part-time Employment: Fight Bladder Cancer,; Financial Interests, Institutional, Funding: Arquer Diagnostics; Financial Interests, Institutional, Funding: Astellas; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Ferring; Financial Interests, Institutional, Funding: Great Bear Healthcare; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Seagen; Non-Financial Interests, Advisory Role: European Oncology Nursing Society Fund; Non-Financial Interests, Advisory Role: Roche; Non-Financial Interests, Member of the Board of Directors: World Bladder Cancer Patient Coalition; Non-Financial Interests, Training: Janssen; Non-Financial Interests, Member: Association of Chief Executives of Voluntary Organisations; Non-Financial Interests, Member: British Association of Urological Nurses; Non-Financial Interests, Member: European Cancer Patient Coalition. H. Lassidi: Financial Interests, Personal, Full or part-time Employment: Roche Products Limited. S. Mariathasan: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. J. Zhang: Financial Interests, Personal, Full or part-time Employment: Hoffmann-La Roche Ltd. V. Degaonkar: Financial Interests, Full or part-time Employment: Roche/Genentech; Financial Interests, Stocks/Shares: Roche/Genentech. J. Bellmunt: Financial Interests, Stocks/Shares: Rainier Therapeutics; Financial Interests, Other, Honoraria: UpToDate; Financial Interests, Advisory Role: Astellas Pharma; Financial Interests, Advisory Role: AstraZeneca/MedImmune; Financial Interests, Advisory Role: Bristol-Myers Squibb; Financial Interests, Advisory Role: Genentech; Financial Interests, Advisory Role: Merck; Financial Interests, Advisory Role: Novartis; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role: Pierre Fabre; Financial Interests, Institutional, Funding: Millennium; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Other, Travel, Accommodations, Expenses: MSD Oncology; Financial Interests, Institutional, Funding: Pfizer/EMD Serono; Financial Interests, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Other, Travel, Accommodations, Expenses: Ipsen.