LBA85 - TAR-200 +/- cetrelimab (CET) and CET alone in patients (pts) with bacillus Calmette-Guérin-unresponsive (BCG UR) high-risk non-muscle-invasive bladder cancer (HR NMIBC): Updated results from SunRISe-1 (SR-1)

Background

Pts with BCG UR HR NMIBC have limited treatment (tx) options. TAR-200 is an intravesical targeted releasing system designed to provide sustained delivery of gemcitabine in bladder over 3 wks. SR-1 (NCT04640623) is an ongoing randomized, ph 2b study evaluating efficacy and safety of TAR-200 + CET (anti-PD-1) (Cohort 1 [C1]), TAR-200 alone (C2), or CET alone (C3) in pts with BCG UR HR NMIBC ineligible for/refusing radical cystectomy. TAR-200 alone is also being assessed in pts with papillary disease only (C4). We report results from C1, C2, and C3.

Methods

Eligible pts (≥18 y) had histologically confirmed carcinoma in situ (CIS) ± papillary disease (high-grade Ta, any T1) with last dose of adequate BCG ≤12 mo of CIS diagnosis, and ECOG PS 0-2. TAR-200 was dosed Q3W to Wk 24 then Q12W to Wk 96. CET was dosed Q3W to Wk 78. Primary end point: complete response (CR) rate at any time. Secondary end points: duration of response (DOR), overall survival, safety and tolerability. Assessments: local cystoscopy, centrally assessed urine cytology Q12W, centrally assessed biopsy at Wks 24/48.

Results

At May 13, 2024 data cutoff, 53 pts in C1, 85 in C2, and 28 in C3 were treated (median age 71.5 y, 80% male, 31% papillary disease). Centrally confirmed CR rates in C1, C2, and C3 were 68%, 84%, and 46%, respectively. Low discontinuation (d/c) rates due to tx-related adverse events (TRAEs) were seen with TAR-200 (C2, 6%) and CET (C3, 7%) alone, with higher rates in the combination (C1, TAR-200 26% or CET 23%). No tx-related deaths occurred. Table: LBA85

Efficacy and safety

^aKaplan-Meier estimates.

Conclusions

TAR-200 monotherapy is highly effective, with the highest single agent CR rate based on published data to date in pts with BCG UR HR NMIBC, durable responses and low d/c rate from TRAEs. CET alone provided modest CR rate comparable to other anti-PD-(L)1 agents. Results from C1, C2, and C3 support the continued development of TAR-200 monotherapy in pts with BCG UR HR NMIBC.

Clinical trial identification

NCT04640623.

Editorial acknowledgement

Writing assistance was provided by Nicolisha Narainpersad, PhD, of Parexel. This study is sponsored by Janssen Research & Development, LLC, a Johnson & Johnson company.

Legal entity responsible for the study

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

Funding

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

Disclosure

M.S. van der Heijden: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas, AstraZeneca, Bristol Myers Squibb, F Hoffmann-La Roche, Janssen Pharmaceuticals, Merck Sharp & Dohme Corporation, Pfizer, Seagen; Financial Interests, Personal, Research Grant: AstraZeneca, Bristol Myers Squibb, F. Hoffmann-La Roche. M. Boegemann: Financial Interests, Personal, Other, Honoraria: Janssen-Cilag, Astellas Pharma, Bayer/Vital, Sanofi/Aventis, MSD, Bristol Myers Squibb, Pfizer, Novartis, Ipsen, EUSA Pharma, Merck, Eisai, Amgen, AstraZeneca, Roche, Advanced Accelerator Applications; Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer, Janssen-Cilag, Astellas Pharma, AstraZeneca, MSD, Bristol Myers Squibb, Ipsen, Roche, Novartis, Merck, Sanofi, Eisai; Financial Interests, Personal, Other, Travel Accommodations: Janssen-Cilag, Bayer, Amgen, BMS GmbH & Co. KG. E. Xylinas: Financial Interests, Personal, Research Grant: Ferring; Financial Interests, Personal, Speaker, Consultant, Advisor: Boston Scientific, Ipsen, Janssen Oncology, MSD, Astellas, AstraZeneca, and Bristol Myers Squibb.. M. Roumiguié: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, AstraZeneca, Pfizer, Janssen Oncology, Bayer, Ferring, and Pierre Fabre. Peter C. Black has consulted for AbbVie, Astellas Pharma, AstraZeneca, EMD-Serono, Ferring, Pfizer, Janssen Oncology, Bayer, Merck, Sanofi Canada, Biosyent, Ferring; Financial Interests, Personal, Research Grant: iProgen; Financial Interests, Personal, Other, Patent: Decipher Biosciences. F. Guerrero-Ramos: Financial Interests, Personal, Research Grant: Combat Medical and Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, AstraZeneca, Johnson and Johnson, Nucleix, Bristol Myers Squibb, Roche, Combat Medical, and Janssen; Financial Interests, Personal, Speaker’s Bureau: Combat Medical, Nucleix, Palex, Astellas, Bristol Myers Squibb, Merck, Janssen, AstraZeneca, and Pfizer; and travel support from Johnson and Johnson, AstraZeneca, Janssen, Ipsen, and Pfizer. A. Necchi: Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Ipsen, BMS, Gilead; Financial Interests, Personal, Steering Committee Member: Roche, Janssen, Bayer, Astellas, AstraZeneca, Merck, Clovis Oncology; Financial Interests, Coordinating PI: Incyte; Financial Interests, Local PI: Pfizer; Non-Financial Interests, Leadership Role: Global society of Rare Genitourinary Tumors (GSRGT). S. Daneshmand: Financial Interests, Personal, Research Grant: Photocure; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Ferring, Janssen, Johnson & Johnson, Olympus, Photocure, Pacific Edge, and QED Therapeutics, Ferring, Photocure, QED Therapeutics, and Taris; honoraria/speaker fees from Aduro Biotech, Allergan; Financial Interests, Personal, Other, Travel Reimbursment: Photocure; Financial Interests, Personal, Stocks or ownership: Taris. P. Spiegelhalder: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen. K. Decaestecker: Financial Interests, Personal, Speaker, Consultant, Advisor: Intuitive Surgical, Medtronic, Conmed, MSD, Bristol Myers Squibb, Bayer, Photocure, and Ipsen; Financial Interests, Personal, Research Grant: Ipsen. D. Zainfeld: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb, and Immunity Bio. S. Hampras, C.J. Cutie, H. Sweiti, K. Stromberg, A. Shukla: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. J. Martin: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Advisory Board: Johnson & Johnson. All other authors have declared no conflicts of interest.