LBA84 - TAR-200 plus cetrelimab (CET) or CET alone as neoadjuvant therapy in patients (pts) with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant cisplatin-based chemotherapy (NAC): Interim analysis of SunRISe-4 (SR-4)

Background

Standard of care for MIBC is radical cystectomy (RC) with NAC, but ∼50% of pts are ineligible for NAC and the 5 y survival for RC alone is ≤50%, indicating a need for new treatments (tx). TAR-200 is an intravesical targeted releasing system designed to provide local sustained gemcitabine within the bladder. SR-4 (NCT04919512) is a randomized ph 2 study assessing the efficacy and safety of neoadjuvant TAR-200 + CET (anti-PD-1) or CET alone in pts with MIBC scheduled for RC who are ineligible/refusing NAC. We report results of a prespecified interim analysis.

Methods

Pts with ECOG PS 0-1, histologically confirmed cT2-T4a N0M0 MIBC, ineligible/refusing NAC, and scheduled for RC were randomized 5:3 to receive TAR-200 + CET (Cohort 1 [C1]) or CET alone (C2), stratified by visibly complete vs incomplete (≤3 cm) resection on TURBT and cT2 vs cT3-4a tumor stage at MIBC diagnosis. Primary outcome measure: pathologic complete response (pCR; ypT0N0) rate. Other outcomes: pathologic overall response (pOR; ≤ ypT1N0) rate and safety.

Results

At May 31, 2024, data cutoff, 120 pts (median age 73 y; 85% male; 20% ECOG PS 1; 81% cT2; 18% residual disease) were treated (C1 n=79; C2 n=41). In efficacy evaluable set, centrally confirmed pCR rates were 42% in C1 and 23% in C2 (pOR rates and cT2 subgroup in the table). 72% of pts in C1 and 44% in C2 had tx-related adverse events (TRAEs), most TRAEs were Gr 1-2. 8% of pts discontinued (d/c) TAR-200 and 8% d/c CET in C1 due to TRAEs; 0% d/c due to TRAEs in C2. Table: LBA84

Efficacy results

Conclusions

TAR-200 + CET neoadjuvant therapy revealed compelling pCR and pOR rates, with a manageable safety profile, supporting the addition of TAR-200 to anti-PD-1 tx in pts with MIBC. In the cT2 subgroup, >2/3 pts who received TAR-200 + CET tx were downstaged to ≤ T1 at RC and ∼1/2 pts achieved pCR. SR-4 interim results support further investigation of TAR-200 + CET in pts with MIBC.

Clinical trial identification

NCT04919512.

Editorial acknowledgement

Medical writing assistance was provided by Flint Stevenson-Jones, PhD, of Parexel, and was funded by Janssen Global Services, 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

A. Necchi: Financial Interests, Personal, Research Grant: Merck, Gilead, Bristol Myers Squibb; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Roche, Bayer, AstraZeneca, Astellas, BMS, Janssen, Pfizer, Incyte. F. Guerrero-Ramos: Financial Interests, Personal, Research Funding: 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; Financial Interests, Personal, Other, Travel Support: Johnson and Johnson, AstraZeneca, Janssen, Ipsen, and Pfizer.. B. Herrera Imbroda: Financial Interests, Personal, Research Grant: Johnson and Johnson and Myriad Genetics; Financial Interests, Personal, Speaker, Consultant, Advisor: Johnson and Johnson, Astellas, Bayer, Ipsen, Recordati, Accord, Novartis, MSD, Bristol Myers Squibb, AstraZeneca and GSK; Financial Interests, Personal, Other, Travel Support: Johnson and Johnson, Astellas, Bayer, Ipsen, Recordati and AstraZeneca.. R. garje: Financial Interests, Institutional, Research Funding: Exelixis and Janssen oncology. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Other, honoraria: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai; Financial Interests, Institutional, Other, Honoraria: Gilead. C.C. Peyton: Financial Interests, Personal, Speaker, Consultant, Advisor: UroGen Pharmaceutica. B. Pradere: Financial Interests, Personal, Speaker, Consultant, Advisor: Ipsen, Johnson and Johnson, MSD, Astellas, Bristol Myers Squibb, Photocure, Kranus Health, Pfizer, Ferring. N.D. Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Cold Genesys, Dendreon, Exact Imaging, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Propella, Sanofi Genzyme, Speciality Networks, Tolmar, Urogen, Clarity, Lantheus, Lilly, Photocure, Telix, Photocure, Asieris, Alessa Therapeutics, Arquer, Fize Medical, GConcology, Guardant, Ferring, Foundation Medicine, Immunitybio, Incyte, Minomic, NGM, Nonagen, Novartis, PlatformQ, Promaxo, Protara, Accord, Antev, Aura Biosciences, Sumitomo; Financial Interests, Personal, Member of Board of Directors: Photocure, Alessa Theraputics; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Bayer, Aura, Exact Imaging, Janssen, Merck, Myovant, Novartis, Pfizer, Propella, Bristol Myers Squibb, Dendreon, Pfizer, Urogen; Financial Interests, Institutional, Local PI: Alessa, GC oncology, FORMA therapeutics, Pacific Edge, Point Biopharma, The MT group, Theralase, Verity, Astellas, Palette Life Sciences, Steba, Zenflow. 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 Research Funding: Janssen-Cilag, Ipsen (Inst); Financial Interests, Personal, Research Funding: Janssen-Cilag, Ipsen (Inst); Financial Interests, Personal, Other, Travel Accommodations: Janssen-Cilag, Bayer, Amgen, BMS GmbH & Co. KG. M.A. Preston: Financial Interests, Personal, Speaker, Consultant, Advisor: NIH, DOD, Merck; Financial Interests, Personal, Advisory Board: Janssen, Pfizer. E. Xylinas: Financial Interests, Personal, Research Funding: Ferring; Financial Interests, Personal, Speaker, Consultant, Advisor: Boston Scientific, Ipsen, Janssen Oncology, MSD, Astellas, AstraZeneca, and Bristol Myers Squibb. C. Gong, S. Najmi, M. Hasan, H. Stitou, S. Bhanvadia, H. Sweiti: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. S.P. Psutka: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen, Medronic, and Merck; Financial Interests, Personal, Other, Honoraria: AstraZeneca. All other authors have declared no conflicts of interest.