1980P - Association of PD-L1 expression with clinical response to TAR-200 in the phase IIb SunRISe-1 trial

Background

Recurrent non-muscle-invasive bladder cancer (NMIBC) tumors after BCG treatment are characterized by an immunosuppressive environment and increased PD-L1 expression. SunRISe-1 (NCT04640623) is an ongoing randomized, phase 2b study assessing efficacy and safety of TAR-200 + cetrelimab (CET) (anti-PD1) (Cohort 1 [C1]), TAR-200 alone (C2), or CET alone (C3) in pts with BCG-unresponsive high-risk (HR) NMIBC with carcinoma in situ (CIS), with or without papillary disease, who are ineligible for or refusing radical cystectomy. TAR-200 alone is also being assessed in BCG-unresponsive papillary-only HR NMIBC (C4). We previously reported C2 clinical results showing that TAR-200 monotherapy provides clinically meaningful efficacy and a favorable benefit-risk profile. This study evaluated whether there is an association between PD-L1 expression and response to TAR-200 monotherapy. Tumor mutational burden (TMB) and microsatellite instability (MSI) were also measured.

Methods

Tumor tissue was collected during screening by transurethral resection of bladder tumor or bladder biopsy from C2 in pts enrolled in SunRISe-1. PD-L1 was measured by immunohistochemistry (22C3) and scored for combined positive scores (CPS) with cutoffs of 1 and 10. DNA isolation and sequencing using the Illumina TSO-500 panel measured TMB and MSI scores.

Results

PD-L1 expression was measured in a subset of 27 pts in C2 with available tumor, with 26 yielding PD-L1 results. Of these, 12 (46%) tumors had PD-L1 CPS measurements ≥10 and 17 (65%) had CPS scores ≥1. As of a January 2, 2024 cutoff, 21 pts with PD-L1 data were evaluable for clinical efficacy. In the efficacy-evaluable population for TAR-200 monotherapy, we observed a CR rate of 81.0% (17/21). We observed a CR rate (95% CI) of 90.9% (58.7%-99.8%) in the CPS≥10 subgroup and 70% (34.8%-93.3%) in the CPS<10 subgroup. CR rates in the CPS≥1 and the CPS<1 subgroups were similar, 80% (51.9%-95.6%) and 83.3% (35.8%-99.6%), respectively.

Conclusions

In this study of SunRISe-1 PD-L1 expression limited by small sample size and number of clinical events, we observed high clinical response to TAR-200 monotherapy in HR NMIBC pts with BCG-unresponsive CIS irrespective of PD-L1 status.

Clinical trial identification

NCT04640623.

Editorial acknowledgement

Medical writing assistance was provided by Ira Mills, PhD, of Parexel, and was funded by Janssen Global Services, LLC. Data analysis assistance was provided by Rui Hong, PhD, of Janssen Research and Development, LLC.

Legal entity responsible for the study

Janssen Research & Development, LLC, a Johnson & Johnson Company.

Funding

Janssen Research & Development, LLC, a Johnson & Johnson Company.

Disclosure

E. Xylinas: Financial Interests, Personal, Research Grant: Ferring; Financial Interests, Personal, Speaker, Consultant, Advisor: Boston Scientific, Ipsen, Janssen Oncology, MSD, Astellas, AstraZeneca, Bristol Myers Squibb. C. Pieczonka: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, AstraZeneca Pharmaceuticals LP, Bayer Healthcare Pharmaceuticals Inc, Dendreon Pharmaceuticals LLC, Janssen Biotech Inc, Merck Sharp & Dohme Corporation, Pfizer, Sumitomo Dainippon Pharma Co Ltd, Sun Pharmaceutical Industries Inc. A. Necchi: Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Gilead, Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Incyte, Janssen, Merck, Pfizer, Roche. S. Daneshmand: Financial Interests, Personal, Research Grant: Photocure; Financial Interests, Personal, Speaker, Consultant, Advisor: Ferring, Photocure, QED Therapeutics, Taris; honoraria/speaker fees from Aduro Biotech, Allergan (immediate family member), Bristol Myers Squibb, Ferring, Janssen, Johnson & Johnson, Olympus, Photocure, Pacific Edge, QED Therapeutics; Financial Interests, Personal, Other, Travel Reimbursement: Photocure; Financial Interests, Personal, Stocks or ownership: Taris. K. Decaestecker: Financial Interests, Personal, Speaker, Consultant, Advisor, Travel Reimbursment: Intuitive Surgical, Medtronic, Conmed, MSD, Bristol Myers Squibb, Bayer, Photocure, Ipsen; Financial Interests, Personal, Research Grant: Ipsen. G. Kulkarni: Financial Interests, Personal, Research Grant: Janssen, Janssen, MSD, Astellas, AstraZeneca, EMD Serono, Pfizer, Ferring, Theralase, Verity, Knight Pharmaceuticals, Tolmar, Photocure, Bristol Myers Squibb. M. Boegemann: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen Cilag, Astellas, Sanofi, Bayer. F. Guerrero-Ramos: Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, Janssen, Roche, Combat Medical; Financial Interests, Personal, Other, Honoraria: Combat Medical, Janssen, Pfizer, Financial Interests, Personal, Advisory Board: Janssen, Pfizer, Bristol Myers Squibb, AstraZeneca. J. Callaway, N. Beeharry, J. Zhang, S. Hampras, H. Sweiti, K. Stromberg, J. Martin, A. Shukla, P. Raciti: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. M.S. van der Heijden: Financial Interests, Personal, Research Grant: 4SC, AstraZeneca, Bristol Myers Squibb, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Janssen, MSD/Merck, Pfizer, Seagen. All other authors have declared no conflicts of interest.