83P - Evaluation of concordance between PD-L1 immunohistochemistry 28-8 and 22C3 pharmDx assays in metastatic urothelial carcinoma (mUC) in PIVOT-10

Background

PD-L1 testing of CPIs guides treatment decisions for mUC pts. However, there are different assays and methods. The tumor proportion score (TPS) method evaluates PD-L1 tumor cells, whereas combined positive score (CPS) captures tumor and immune cells. Two assays, PD-L1 immunohistochemistry (IHC) 22C3 (CPS) and 28-8 pharmDx (TPS) are approved for pembrolizumab and NIVO, respectively. In PIVOT-10, a phase 2 study of bempegaldesleukin + NIVO in cis-ineligible mUC, both assays are being tested contemporaneously to explore concordance.

Methods

Pts without prior systemic therapy or recurrence >12 mo from perioperative chemotherapy were eligible. Archival baseline tumor (≤12 mo prior to enrollment) or fresh samples (N=259) were tested using both assays and scored using CPS (no. of PD-L1-stained cells [tumor cells, lymphocytes, macrophages]/ total no. of viable tumor cells x 100). Samples were analyzed using a CPS cut-off < vs ≥10 and concordance was analyzed statistically.

Results

There was agreement between the assays (absolute mean difference= 0.96 [Lin’s Concordance Correlation Coefficient]). Similar % of PD-L1-low tumors were seen (28-8: 68%; 22C3: 67%) and binary results showed good quality of agreement (Cohen’s k value: 0.89). The overall % agreement (OPA), +ve % agreement (PPA), and –ve % agreement (NPA) (22C3 or 28-8 assay as ref) were 95%, 93%, and 97%, respectively (Table). Table: 83P

Agreement between the 28-8 and 22C3 assays in matched samples* in the overall population (CPS 10 cut-off)

*Pts with matched biopsy and single test results for 28-8 and 22C3 assays.CI, confidence interval; CPS, combined positive score; NPA, negative (–ve) % agreement; OPA, overall % agreement; PPA, positive (+ve) % agreement.

Conclusions

When evaluated in the controlled setting of a clinical trial, the PD-L1 IHC 22C3 and 28-8 pharmDx assays detected similar rates of PD-L1-low tumors in baseline biopsies from mUC pts and demonstrated high concordance at CPS cut-off < vs ≥10. This study is unique in that it was conducted contemporaneously on fresh or recently obtained archival tumors. These data suggest high concordance and potential interchangeability of the 28-8 and 22C3 assays for evaluating baseline PD-L1 status, based on CPS, for mUC pts.

Clinical trial identification

NCT03785925. Trial protocol: 18-214-10 / CA045-012 (February 6, 2020).

Editorial acknowledgement

Medical writing and editorial assistance was provided by Alison Lovibond PhD of Boldscience Inc. funded by Nektar Therapeutics.

Legal entity responsible for the study

Nektar Therapeutics, San Francisco, CA and Bristol Myers Squibb, Princeton, NJ.

Funding

This study is sponsored by Nektar Therapeutics, San Francisco, CA and Bristol Myers Squibb, Princeton, NJ.

Disclosure

A.O. Siefker-Radtke: Other, Personal, Advisory Role: Janssen; Other, Personal, Advisory Role: Merck; Other, Personal, Advisory Role: NCCN; Other, Personal, Advisory Role: Bristol Myers Squibb; Other, Personal, Advisory Role: AstraZeneca; Other, Personal, Advisory Role: Bavarian Nordic; Other, Personal, Advisory Role: Seattle Genetics; Other, Personal, Advisory Role: Nektar Therapeutics; Other, Personal, Advisory Role: Genentech; Other, Personal, Advisory Role: EMD Serono; Other, Personal, Advisory Role: Mirati Therapeutics; Other, Personal, Advisory Role: Basilea; Other, Personal, Licensing Fees, Methods of characterizing and treating molecular subsets of muscle-invasive bladder cancer: Patents, Royalties, Other Intellectual Property; Financial Interests, Personal, Funding, Research Funding: NIH; Financial Interests, Personal, Funding, Research Funding: Michael and Sherry Sutton Fund for Urothelial Cancer; Financial Interests, Personal, Funding, Research Funding: Janssen; Financial Interests, Personal, Funding, Research Funding: Takeda; Financial Interests, Personal, Funding, Research Funding: Bristol Myers Squibb; Financial Interests, Personal, Funding, Research Funding: BioClin Therapeutics; Financial Interests, Personal, Funding, Research Funding: Nektar Therapeutics; Financial Interests, Personal, Funding, Research Funding: Merck Sharp & Dohme; Financial Interests, Personal, Funding, Research Funding: Basilea. U. Hoch: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. Y. Loriot: Other, Personal, Advisory Role: Janssen; Other, Institutional, Advisory Role: Janssen; Other, Personal, Advisory Role: Astellas Pharma; Other, Personal, Advisory Role: Roche; Other, Personal, Advisory Role: MSD Oncology; Other, Institutional, Advisory Role: MSD Oncology; Other, Personal, Advisory Role: Seattle Genetics; Other, Personal, Advisory Role: Bristol Myers Squibb; Other, Personal, Advisory Role: Immunomedics; Other, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Astellas Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Seattle Genetics; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Institutional, Funding, Research Funding: Sanofi; Financial Interests, Institutional, Funding, Research Funding: Janssen Oncology; Financial Interests, Institutional, Funding, Research Funding: MSD Oncology; Financial Interests, Institutional, Funding, Research Funding: AstraZeneca; Financial Interests, Institutional, Funding, Research Funding: Clovis Oncology; Financial Interests, Institutional, Funding, Research Funding: Exelixis; Financial Interests, Institutional, Funding, Research Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding, Research Funding: Incyte; Financial Interests, Institutional, Funding, Research Funding: Pfizer; Financial Interests, Institutional, Funding, Research Funding: Oncogenex; Financial Interests, Institutional, Funding, Research Funding: Medivation; Financial Interests, Institutional, Funding, Research Funding: CureVac; Financial Interests, Institutional, Funding, Research Funding: Nektar Therapeutics. A.V. Balar: Other, Personal, Advisory Role: Genentech; Other, Personal, Advisory Role: Merck; Other, Personal, Advisory Role: Cerulean Pharma; Other, Personal, Advisory Role: AstraZeneca/MedImmune; Other, Personal, Advisory Role: Pfizer/EMD Serona; Other, Personal, Advisory Role: Incyte; Other, Personal, Advisory Role: Seattle Genetics/Astellas; Other, Personal, Advisory Role: Nektar Therapeutics; Other, Personal, Advisory Role: Dragonfly Therapeutics; Other, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Genentech/Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune; Financial Interests, Institutional, Funding, Research Funding: Merck; Financial Interests, Institutional, Funding, Research Funding: Genentech/Roche; Financial Interests, Institutional, Funding, Research Funding: AstraZeneca/MedImmune; Financial Interests, Personal, Funding, Research Funding: Seattle Genetics. M.A. Bilen: Other, Personal, Advisory Role: Exelixis; Other, Personal, Advisory Role: Sanofi; Other, Personal, Advisory Role: Nektar Therapeutics; Other, Personal, Advisory Role: EMD Serono; Other, Personal, Advisory Role: Eisai; Other, Personal, Advisory Role: Janssen; Other, Personal, Advisory Role: Genomic Health; Other, Personal, Advisory Role: Seattle Genetics; Other, Personal, Advisory Role: Pfizer; Other, Personal, Advisory Role: Bristol Myers Squibb; Other, Personal, Advisory Role: Bayer; Other, Personal, Advisory Role: Calithera Biosciences; Financial Interests, Institutional, Funding, Research Funding: Bayer; Financial Interests, Institutional, Funding, Research Funding: Brtisol-Myers Squibb; Financial Interests, Institutional, Funding, Research Funding: Genentech/Roche; Financial Interests, Institutional, Funding, Research Funding: Incyte; Financial Interests, Institutional, Funding, Research Funding: Nektar Therapeutics; Financial Interests, Institutional, Funding, Research Funding: AstraZeneca; Financial Interests, Institutional, Funding, Research Funding: Tricon Pharmaceuticals; Financial Interests, Institutional, Funding, Research Funding: Pfizer; Financial Interests, Institutional, Funding, Research Funding: Seattle Genetics; Financial Interests, Institutional, Funding, Research Funding: Xencor; Financial Interests, Institutional, Funding, Research Funding: Exelixis; Financial Interests, Institutional, Funding, Research Funding: Advanced Accelerator Applications; Financial Interests, Institutional, Funding, Research Funding: Genome & Company; Financial Interests, Institutional, Funding, Research Funding: Peloton Therapeutics; Other, Personal, Advisory Role: Exelixis. N.M. Tannir: Other, Personal, Advisory Role: Novartis; Other, Personal, Advisory Role: Exelixis; Other, Personal, Advisory Role: Bristol Myers Squibb; Other, Personal, Advisory Role: Nektar Therapeutics; Other, Personal, Advisory Role: Pfizer; Other, Personal, Advisory Role: Eisai; Other, Personal, Advisory Role: Ono Pharmaceutical; Other, Personal, Advisory Role: Oncorena; Other, Personal, Advisory Role: Surface Oncology; Other, Personal, Advisory Role: Neoleukin Therapeutics; Other, Personal, Advisory Role: Ipsen; Other, Personal, Advisory Role: Merck Sharp & Dohme; Other, Personal, Advisory Role: Calithera Biosciences; Other, Personal, Advisory Role: Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Nektar Therapeutics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Eisai; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Surface Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Calithera Biosciences; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Exelixis; Financial Interests, Personal, Other, Honoraria: Nektar Therapeutics; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceuitcal; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Oncorena; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Surface Oncology; Financial Interests, Personal, Other, Honoraria: Neoleukin Therapeutics; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria: Calithera Biosciences; Financial Interests, Personal, Funding, Research Funding: Bristol Myers Squibb; Financial Interests, Personal, Funding, Research Funding: Exelixis; Financial Interests, Personal, Funding, Research Funding: Pfizer; Financial Interests, Personal, Funding, Research Funding: Nektar Therapeutics; Financial Interests, Personal, Funding, Research Funding: Calithera Biosciences; Financial Interests, Personal, Funding, Research Funding: Lilly; Financial Interests, Personal, Funding, Research Funding: Mirati Therapeutics; Financial Interests, Personal, Funding, Research Funding: Arrowhead Pharmaceuticals; Financial Interests, Personal, Funding, Research Funding: Takeda; Financial Interests, Personal, Funding, Research Funding: Epizyme; Financial Interests, Personal, Funding, Research Funding: Eisai. D.C. Cho: Other, Personal, Advisory Role: HUYA Bioscience International; Other, Personal, Advisory Role: Nektar Therapeutics; Other, Personal, Advisory Role: Torque; Other, Personal, Advisory Role: PureTech; Other, Personal, Advisory Role: Pfizer; Other, Personal, Expert Testimony: Genentech; Other, Personal, Expert Testimony: Abbot/AbbVie. A. Choudhury: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. D. Chien: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Stocks/Shares: AbbVie. D. Yu: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. S.L. Currie: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. J. Novotny: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Stocks/Shares: GlaxoSmithKline. L. Santiago: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics; Financial Interests, Personal, Full or part-time Employment: Harpoon Therapeutics. M.A. Tagliaferri: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. J. Zalevsky: Financial Interests, Personal, Full or part-time Employment: Nektar Therapeutics; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics. R.A. Huddart: Other, Personal, Advisory Role: Roche; Other, Personal, Advisory Role: Merck Sharp & Dohme; Other, Personal, Advisory Role: Janssen Oncology; Other, Personal, Advisory Role: Nektar Therapeutics; Other, Personal, Advisory Role: Bayer; Financial Interests, Personal, Leadership Role: Cancer Clinic London LLP; Other, Personal, Speaker’s Bureau: MSD; Other, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Other, Travel/Accommodations, expenses: Roche/Genentech; Financial Interests, Personal, Other, Travel/Accommodations, expenses: Nektar Therapeutics; Financial Interests, Institutional, Royalties, Patents, Royalties, Other Intellectual Property: Jansen; Financial Interests, Institutional, Funding, Research Funding: Merck Sharp & Dohme; Financial Interests, Institutional, Funding, Research Funding: Roche; Financial Interests, Institutional, Funding, Research Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Research Funding: Janssen; Financial Interests, Institutional, Funding, Research Funding: Nektar Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Astellas Pharma; Financial Interests, Institutional, Funding, Research Funding: Basilea.