2407TiP - SunRISe-3: TAR-200 plus cetrelimab (CET) or TAR-200 versus intravesical bacillus Calmette-Guérin (BCG) in patients (pts) with BCG-naive high-risk non-muscle-invasive bladder cancer (HR NMIBC)

Background

Standard of care for pts with HR NMIBC is transurethral resection of bladder tumor (TURBT; biopsy only for carcinoma in situ pts) followed by intravesical BCG. However, BCG is associated with toxicities and supply shortages and lacks a durable response in a significant proportion of pts. TAR-200 is an intravesical drug delivery system that provides local continuous gemcitabine release within the bladder. Preliminary data from SunRISe-1 ( AUA 2023, NCT04640623) support further investigation of TAR-200 with or without CET in pts with BCG-naive HR NMIBC. SunRISe-3 (NCT05714202) is an open-label, multicenter, randomized phase 3 study assessing efficacy and safety of TAR-200 + CET or TAR-200 vs BCG in pts with BCG-naive HR NMIBC.

Trial design

Eligibility: ≥18 y, ECOG PS 0, 1, or 2, histologically confirmed HR NMIBC (high grade Ta, any T1 or CIS) in BCG-naive pts (no prior BCG or stopped >3 y prior to randomization). All papillary disease must be fully resected prior to randomization. Pts (N≈1050) are randomized 1:1:1 to receive TAR-200 + CET (Group A), TAR-200 (Group C) or BCG (Group B). In Groups A and C, TAR-200 (225 mg gemcitabine) is dosed Q3W during an induction phase, then Q12W during a maintenance phase. In Group B, BCG is dosed QW for 6 wks and QW for 3 wks at Wks 12, 24, 48, 72, and 96. Pts may continue in Y3 at investigator discretion. Disease recurrence or progression assessments are by cystoscopy, urine cytology, TURBT/bladder biopsy, and CT/MR urography. The primary end point is event-free survival (time from randomization to HR disease first recurrence [high grade Ta, any T1 or CIS], progression or any-cause death, persistent disease at 6 mo in CIS pts). Progression is defined as increase of stage (Ta to T1, or CIS to T1) or progression to MIBC (T ≥2 or to N+ or M+ disease). Secondary end points include overall complete response rate (CIS only), recurrence-free survival, time to progression, overall survival, cancer-specific survival, safety, and pt-reported outcomes. As of May 3, 2023, 1 pt has been randomized, with 16 in screening; recruitment is planned at 254 sites.

Clinical trial identification

NCT05714202.

Editorial acknowledgement

Medical writing assistance was provided by Ira Mills, PhD, of Parexel and was funded by Janssen Global Services, Llc.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Reseach & Development.

Disclosure

A. Necchi: Financial Interests, Institutional, Research Grant: Merck Gilead BMS; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Merck, Roche, Bayer, AstraZeneca, Astellas, BMS, Janssen, Pfizer, Incyte. J.W.F. Catto: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: AstraZeneca, Ferring, Roche, and Janssen; speaker fees from Bristol Myers Squibb, Merck Sharp & Dohme, Janssen, Astellas, Nucleix, and Roche; Financial Interests, Personal, Advisory Board, Honoraria: Ferring, Roche, Gilead, Photocure, Bristol Myers Squibb, QED Therapeutics, and Janssen; Financial Interests, Personal, Research Funding: Roche. T.B. Powles: Financial Interests, Personal, Research Grant: AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas Pharma, Johnson & Johnson, and Eisai; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: BMS, Merck, AstraZeneca, Ipsen, Pfizer, Novartis, Incyte, Seattle Genetics, Roche, Exelixis, MSD, Merck Serono, Astellas Pharma, Johnson & Johnson, and Eisai; Financial Interests, Personal, Other, Travel: Pfizer, MSD, AstraZeneca, Roche, and Ipsen. MB reports consulting fees from Roche/Genentech, BMS, MSD Oncology, Novartis, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech, MSD Oncology, BMS, and AstraZeneca. BE reports an institutional research grant from BMS; consulting fees from Pfizer, BMS, Ipsen, AVEO, Oncorena, and Eisai; Financial Interests, Personal, Other, Honoraria: Pfizer, BMS, Ipsen, Oncorena, and Eisai; and travel support from BMS, Ipsen, and MSD. F. Guerrero-Ramos: Financial Interests, Personal, Other, Employment: Sermas; Financial Interests, Personal, Research Funding: Combat Medical; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Janssen, Pfizer, Merck, Roche; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Other, Travel Reimbursment: Janssen, Nucleix, Pfizer, Recordati, Ipsen, Combat Medical; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Combat Medical, Janssen, Nucleix, Pfizer, Taris. N.D. Shore: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Bayer, Janssen Scientific Affairs, Dendreon, Tolmar, Ferring, Medivation/Astellas, Amgen, Pfizer, AstraZeneca, Myovant Sciences, Astellas Pharma, AbbVie, Merck, Bristol Myers Squibb/Sanofi, Boston Scientific, Clovis Oncology, Exact Imaging, FerGene, Found; Financial Interests, Personal, Speaker’s Bureau: Janssen, Bayer, Dendreon, Astellas Pharma, AstraZeneca, Clovis Oncology, Pfizer, Guardant Health, Merck, Foundation MedicineResearch Funding: AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Boston Scientific, Clovis Oncolo; Financial Interests, Personal, Advisory Role: AbbVie, Astellas, AstraZeneca, Bayer, Ferring, GE, GSK, Ipsen, Janssen, SanofiSpeakers' Bureau: AbbVie, Astellas, AstraZeneca, Bayer, GE, Janssen, OrionResearch Funding: AbbVie, Astellas, AstraZeneca, Ipsen, JanssenTravel, Accommodations, Expe. A.S. Merseburger: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen Astellas Bayer Merck AstraZeneca Myovant Pfizer Lantheus/progenics; Financial Interests, Personal, Other, Trabve support: AstraZeneca, Astellas, Bayer, Bristol Myers Squibb, Eisai, Ferring, Ipsen, MSD, Merck Serono, Janssen, Takeda, TEVA, Astellas, Novartis, Pfizer, Recordati and Roche. D. Morris: Financial Interests, Personal, Speaker’s Bureau: Janssen Astellas Bayer Merck AstraZeneca Myovant Pfizer Lantheus/progenics. F. Korkes: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Janssen, AstraZeneca, Adium; Financial Interests, Personal, Other, Honoraria: Janssen, AstraZeneca, Adium, Bayer. M. Hasan: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Other, Employment: Janssen. S. Jin, J. Maffeo, C. Hammond, H. Sweiti, R. Somer: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. All other authors have declared no conflicts of interest.