Abstract 1770P
Background
Patients (pts) with locoregional advanced urothelial cancer (n=54) were pre-operatively treated with combined ipilimumab and nivolumab using different dosing regimens. Pts in cohort 1 and 2A were treated with ipilimumab 3 mg/kg (ipi-high) and pts in cohort 2B were treated with ipilimumab 1 mg/kg (ipi-low). A response, defined as ypT0/Tis/Ta, was achieved in 24/38 (63%) pts in the ipi-high cohorts and in 4/14 (29%) pts in the ipi-low cohort. Here, we present updated follow-up data and an exploratory biomarker analysis to better understand the difference between ipi-low and ipi-high. Using a multiplex PCR-based NGS assay (RaDaR), we aim to confirm pre-operative plasma ctDNA detection to predict response in cohort 1.
Methods
Somatic variants associated with response were investigated using WES on baseline tumor and whole blood DNA. Plasma ctDNA status was evaluated using the RaDaR assay. Baseline PD-L1 was determined by IHC using the 22C3 pharmDx test. Tumor immune cell infiltration was studied using multiplex immunofluorescence (mIF).
Results
In an updated survival analysis (cutoff March 2022), progression-free survival was numerically better in the ipi-high cohorts (cohort 1: 85% at 1yr and 2yr; cohort 2A: 75% at 1yr) vs ipi-low (cohort 2B 55% at 1yr; p=0.0880). At this early analysis, especially for cohort 2, OS was similar in ipi-high cohorts (cohort 1+2A: 90% at 1yr) vs the ipi-low cohort (cohort 2B: 85% at 1yr; ipi-high vs ipi-low p=0.7185).
Response rate in the ipi-high cohort was 69.6% in the PD-L1 positive group vs 42.9% in the PD-L1 negative group, and 42.8%% in the PD-L1 positive group vs 14.3% in the PD-L1 negative group in the ipi-low cohort.
In cohort 1, plasma ctDNA was undetectable after pre-operative treatment in 13/14 responders and in 4/10 non-responders (p=0.0088; presented AACR 2022). Confirmation of these observations on cohort 2 as well as mIF data on immune cell subsets are pending.
Conclusions
Pre-operative ipi+nivo stage III UC, particularly in the ipi-high cohorts, leads to encouraging PFS. PD-L1 does not predict response in ipi-high pts. Conclusions of the pending assays will be presented at the ESMO meeting.
Clinical trial identification
NCT03387761.
Editorial acknowledgement
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Bristol Myers Squibb.
Disclosure
C. Pipinikas, G. Jones, N. Rosenfeld: Financial Interests, Other, Ltd.: Inivata. J. de Feijter: Financial Interests, Personal and Institutional, Advisory Board: Janssen, Merck, Pfizer; Financial Interests, Personal and Institutional, Other, Travel expenses: Pfizer. R. Meijer: Financial Interests, Institutional, Advisory Role: Merck, MSD, Janssen, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Janssen, Astellas, Roche. N. Mehra: Financial Interests, Personal and Institutional, Advisory Board: Roche, MSD, Bristol Myers Squibb, Bayer, Astellas, Janssen; Financial Interests, Institutional, Funding: Astellas, Bristol Myers Squibb, Pfizer, Roche, Sanofi, Genzyme. B.B. Suelmann: Financial Interests, Personal and Institutional, Advisory Role: Pfizer, MSD, BMS, Novartis, Ipsen; Financial Interests, Institutional, Research Grant: Pfizer, Astellas, BMS. B.W.G. van Rhijn: Financial Interests, Institutional, Advisory Board: Ferring, QED Therapeutics. M.S. van der Heijden: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Jansssen, MSD, Pfizer, Seagen; Non-Financial Interests, Institutional, Other, Investigator-initiated trial: 4SC; Non-Financial Interests, Institutional, Other, Steering Committee Member, Local PI + SSC member: AstraZeneca, BMS; Non-Financial Interests, Institutional, Funding, Investigator-initiated trial: AstraZeneca, BMS; Non-Financial Interests, Institutional, Principal Investigator, Local PI: GSK, Seagen; Non-Financial Interests, Institutional, Other, Steering committee member, local PI + study co-PI: Janssen, MSD; Non-Financial Interests, Institutional, Funding, Investigator initiated trial: Roche. All other authors have declared no conflicts of interest.