1735O - PD-L1 expression on immune cells by SP142 co-localises with dendritic cells and is associated with improved overall survival (OS) with atezolizumab in patients with untreated metastatic urothelial cancer (mUC)

Background

PD-L1 assays use various methods (e.g., scoring tumour and/or immune cells) to predict PD-L1/PD-1 blockade outcomes. Data suggest that the clinically relevant PD-L1–expressing immune cells (IC) are dendritic cells (DCs) (Oh 2020). Here, we probed the clinical and immunologic basis underlying the trend toward favourable OS with atezolizumab alone (atezo; anti–PD-L1; Arm B) vs placebo + platinum/gemcitabine chemotherapy (chemo; Arm C) in patients (pts) with high PD-L1 by SP142 in the Ph 3 IMvigor130 trial (ITT: HR, 0.68, 95% CI: 0.43, 1.08; cisplatin ineligible: HR, 0.53, 95% CI: 0.30, 0.94) (Galsky ASCO-GU 2021; 31 May 2019 cutoff).

Methods

This post hoc analysis studied associations between 2 PD-L1 immunohistochemistry tests (VENTANA SP142 and Dako 22C3) and OS in pts with archival tumours (biomarker-evaluable [BioEval] pts) in IMvigor130 Arms B and C (14 Jun 2020 cutoff). Assay cutoffs were SP142 IC ≥5% (IC2/3)/<5% (IC0/1) and 22C3 combined positive score (CPS) ≥10/<10. Samples were also stained for IC subtypes.

Results

Demographics and OS of BioEval (n=627) and ITT (n=719) pts were similar. In deconvoluting the cellular components associated with PD-L1 staining, we found that SP142 preferentially co-localised with DCs (DC-LAMP, a DC-specific marker) as opposed to other myeloid subsets. Arm B OS by SP142 and/or 22C3 is shown in the table. Longer OS was associated with SP142 IC2/3 + 22C3 CPS ≥10 tumour status. Median OS was shortest in pts with tumours staining for 22C3 but not SP142 (SP142 IC0/1 + 22C3 CPS ≥10; Table).

Conclusions

This IMvigor130 exploratory analysis showed different OS trends with different PD-L1 assays. PD-L1–expressing DCs may underlie the longer OS with atezo in SP142 IC2/3 vs IC0/1 tumours in pts with mUC. These findings reinforce model system data demonstrating the particular importance of PD-L1–expressing DCs. Table: 1735O

Clinical trial identification

NCT02807636.

Editorial acknowledgement

Medical writing assistance was provided by Bena Lim, PhD, of MediTech Media 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

E. Grande Pulido: Financial Interests, Personal, Invited Speaker: Adacap, AstraZeneca, Bristol Myers Squibb, Eisai, Eusa Pharma, IPSEN, Janssen, Lilly, Merck KGa, Pfizer, Roche; Financial Interests, Personal, Advisory Board: Astellas, Bayer, MSD, Novartis, Sanofi-Genzyme; Financial Interests, Institutional, Advisory Board: Caris Life Sciences, ONCODNA (Biosequence); Financial Interests, Institutional, Research Grant, Independent research grant: Astellas, AstraZeneca, Lexicon, MTEM/Threshold, Nanostring Technologies, Pfizer, Roche, Merck; Financial Interests, Institutional, Invited Speaker, Independent research grant: Ipsen; Non-Financial Interests, Other, AD BOARD member: ENETS. M.D. Galsky: Financial Interests, Personal, Advisory Board: Janssen, Merck, GlaxoSmithKline, Eli Lilly, Astellas, Genentech, Bristol Myers-Squibb, Pfizer, EMD Serono, AstraZeneca, Seagen, Incyte, Alligator; Financial Interests, Personal, Other, Consultant: Rappta Therapeutics; Financial Interests, Institutional, Invited Speaker: Merck, AstraZeneca, Genentech, Jazz, Bristol Myers Squibb, Seagen. R. Van Elzen: Financial Interests, Personal, Full or part-time Employment: CellCarta. R. Banchereau: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. M. Peterson, C. Sedano, I. Mellman, S. Oh: Financial Interests, Personal, Full or part-time Employment: Genentech. H. Koeppen: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. H. Li, S. Bernhard, C.P. Lee: Financial Interests, Personal, Full or part-time Employment: Roche. A. Bamias: Financial Interests, Personal, Invited Speaker: Ipsen, Debiopharm; Financial Interests, Personal, Advisory Board: BMS, MSD, AstraZeneca; Financial Interests, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Roche, BMS, MSD; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer; Non-Financial Interests, Leadership Role: Hellenic GU Cancer Group. J.A. Arranz Arija: Financial Interests, Personal, Advisory Board: Astellas, BMS, Merck, Pfizer, Bayer, MSD, EISAI; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker, SOGUG: BMS. E. Kikuchi: Financial Interests, Personal, Other, Honoraria: Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Janssen, Kissei, Kyorin, Merck Biopharma, MSD, Nippon Kayaku, Nippon Shinyaku, Pfizer, Sanofi, Taiho, Takeda, Kyowa Kirin; Financial Interests, Personal, Advisory Role: Merck Biopharma, Astellas, Chugai, Bristol Myers Squibb; Financial Interests, Institutional, Sponsor/Funding: Kissei, Takeda, Taiho, Nippon Kayaku, Nippon Shinyaku. M. De Santis: Financial Interests, Personal, Advisory Board, Advisory functions, invited speaker,: Bioclin; Financial Interests, Personal, Advisory Board: AAA, Amgen, 4D, EISAI, Basilea, Merck/Serono, Bayer, BMS, Sanofi, Ipsen, Novartis/Sandoz, Immunomedics/Gilead, Roche, Ferring, SeaGen; Financial Interests, Personal, Advisory Board, invited speaker, advisory function: Astellas; Financial Interests, Personal, Advisory Board, invited speaker, steering committee member: AstraZeneca; Financial Interests, Personal, Advisory Board, invited speaker, advisory function, local PI: MSD; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board, Speaker fees: Pierre Fabre Oncology; Financial Interests, Personal, Invited Speaker, Steering committee, advisory Board: AAA; Financial Interests, Personal, Invited Speaker, advisory function: Amgen; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria: Astellas, AstraZeneca, 4D, Bayer, Novartis, Ipsen, Janssen; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria trial fees: EISAI; Financial Interests, Personal and Institutional, Invited Speaker, local PI, honoraria for advisory function, trial fees: Basilea; Financial Interests, Institutional, Invited Speaker: Calithera; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, local PI, honoraria, trial fees: MSD; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria,: Merck/Serono; Financial Interests, Personal and Institutional, Invited Speaker, Advisory function, honoraria, travel funding: BMS; Financial Interests, Institutional, Invited Speaker, trial fees: Nektar; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria: Sanofi; Financial Interests, Personal and Institutional, Invited Speaker, Advisory function, honoraria: Roche/Genentech; Financial Interests, Personal, Invited Speaker, advisory function, honoraria: Sandoz; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, local PI: Immunomedics/Gilead; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria, local PI: SeaGen; Financial Interests, Personal, Other, advisory function, honoraria: Ferring; Financial Interests, Personal and Institutional, Invited Speaker, advisory function, honoraria, local and coordinating PI: Pierre Fabre; Non-Financial Interests, Member, writing and discussing guidelines for treatment and diagnostics: EAU Guidelines group prostate cancer; Non-Financial Interests, Member, Guidelines for bladder cancer treatment: S3 Leitlinie Blasenkrebs; Non-Financial Interests, Member: ESMO Clinical practice guidelines panel bladder cancer. I.D. Davis: Financial Interests, Personal, Royalties, Authorship royalties for: Health Press; Financial Interests, Personal, Other, Remuneration for associate editor role in Therapeutic Advances in Medical Oncology: SAGE; Financial Interests, Institutional, Invited Speaker, Institutional support for clinical research: Movember Foundation, Merck/MSD, Bristol Myers Squibb, Exelixis, Astellas, Pfizer, AstraZeneca, Roche / Genentech, Eisai, Bayer, Janssen, Ipsen, Seagen; Non-Financial Interests, Invited Speaker, Director and Chair: ANZUP Cancer Trials Group; Non-Financial Interests, Advisory Role, All honoraria and payments are made directly to ANZUP Cancer Trials Group with no pass-through payment: Roche, Janssen, Astellas, Bayer, Ipsen, MSD, Merck/Pfizer, AstraZeneca, Eisai, Bristol Myers Squibb, Pio Therapeutics; Non-Financial Interests, Other, Member of Council: Clinical Oncology Society of Australia. P. Williams: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech/Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Genentech. M. Kockx: Financial Interests, Personal, Member of the Board of Directors: CellCarta; Financial Interests, Personal, Stocks/Shares: CellCarta. S. Mariathasan: Financial Interests, Full or part-time Employment: Genentech; Financial Interests, Stocks/Shares: Genentech.