Urinary Bladder Neoplasms

The purpose of this study is to evaluate the overall complete response (CR) rate in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease; and disease-free survival (DFS) in participants treated with TAR-200 alone with papillary disease only (Cohort 4).

A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guérin Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy

Bladder Cancer

Genitourinary Cancer

Advanced Solid Tumors

Prostate Neoplasms

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

Cetrelimab

TAR-200

Phase 2b Clinical Study Evaluating Efficacy and Safety of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guérin (BCG) Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy

Overall CR rate was defined as the percentage of participants who met at least one of the following: negative cystoscopy and negative (including atypical) centrally read urine cytology, or positive cystoscopy with biopsy-proven benign or low-grade non-muscle invasive bladder cancer (NMIBC) and negative (including atypical) centrally read cytology at any time point.

DFS was defined as the time from the date of first dose of study treatment to the time of one of the following events, whichever occurred first: (1) The first recurrence of high-risk disease (high-grade Ta, any T1 or CIS), (2) progression to muscle invasive bladder cancer (MIBC) (T greater than or equal to [>=] 2) or to lymph node (N+) or to distant disease (M+), whichever occurred first, (3) Death due to any cause.

DOR was defined as the date of first complete response (CR) achieved to the date of first evidence of recurrence or progression or death, using cystoscopy, centrally read bladder biopsy and urine cytology, and imaging, if available. Complete response was defined as having a negative cystoscopy and negative (including atypical) centrally assessed urine cytology, or positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative (including atypical) centrally assessed cytology at any time point. Number of participants with at least 12 months duration of response were reported.

Plasma concentrations of gemcitabine and dFdU were reported.

Cmax was defined as maximum observed urine concentration.

Urine concentrations of gemcitabine and dFdU were reported.

Serum concentration of cetrelimab were reported.

Number of participants positive to anti-cetrelimab antibodies was reported using validated immunoassay for anti-drug antibody (ADA) analysis.

TAR-200 is placed into the bladder through a urinary placement catheter in participants with carcinoma in situ (CIS), with or without papillary disease, on Day 0 and will be dosed every 3 weeks (Q3W) for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2). In addition, Cetrelimab will be dosed Q3W through Week 78 (18 months).

TAR-200 is placed into the bladder through a urinary placement catheter in participants with CIS, with or without papillary disease, on Day 0 and will be dosed Q3W for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2).

Participants with CIS, with or without papillary disease, will receive Cetrelimab which will be dosed Q3W through Week 78 (18 months).

TAR-200 is placed into the bladder through a urinary placement catheter in participants with papillary disease only, on Day 0 and will be dosed Q3W for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2).

The purpose of this study is to evaluate the overall complete response (CR) rate in
      participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone
      (Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without
      concomitant high-grade Ta or T1 papillary disease; and disease-free survival (DFS) in
      participants treated with TAR-200 alone with papillary disease only (Cohort 4).

Urological Associates of Southern Arizona, P.C.

University of Southern California

The Urology Center of Colorado

Foothills Urology - Golden Off

DuPage Medical Group

Michigan Institute of Urology

NYU Langone Health

SUNY Upstate Medical University

Associated Medical Professionals

Levine Cancer Institute

The Urology Group

Urologic Consultants of Southeastern Pennsylvania

Thomas Jefferson University

Urology Associates, PC

Vanderbilt University Medical Center

University of Texas Southwestern Medical Center

Urology San Antonio Research

Spokane Urology

Flinders Medical Centre

Eastern Health Research

Macquarie University Hospital

Algemeen Ziekenhuis Sint-Jan

AZ St.-Jan Brugge-Oostende AV

Hopital Erasme

Universitair Ziekenhuis Gent

Algemeen Ziekenhuis Delta

AZ Nikolaas

Exdeo Clinical Research Inc

William Osler Health System

Princess Margaret Hospital- UHN

McGill University Health Centre

Universite de Sherbrooke

Polyclinique Bordeaux Nord Acquitaine

CHU Grenoble

Clinique Sainte Marguerite

Polyclinique de Limoges - Francois Chenieux

Hôpital Edouard Herriot

Institut Paoli-Calmettes

CHU Nîmes

Hôpital Universitaire Pitié-Salpêtrière

Hopital Saint-Louis

Hopital Europeen Georges-Pompidou

Groupe Hospitalier Diaconesses Croix Saint Simon

Hopital Bichat Claude Bernard

Hopital Pontchaillou

CHP Saint Gregoire

Institut de Cancerologie Strasbourg Europe (ICANS)

Hopital Foch

Hopital Rangueil

Urologicum Duisburg

Klinikum Herne - Urologie

Urologische Partnerschaft Köln UPK

Matthias Schulze - Germany

Urologie Neandertal Praxis Mettmann

Universitätsklinikum Münster

Schön Klinik Nürnberg Fürth

Studienpraxis Urologie Nürtingen - Germany

Urologische Praxis am Wasserturm - Germany

Metropolitan General A.E.

Athens Medical Center

Bioclinic - Thessaloniki

General Hospital of Thessaloniki G. Gennimatas

Euromedica General Clinic

'Papageorgiou' General Hospital of Thessaloniki

Azienda Ospedaliera Universitaria Careggi

Ospedale San Martino

Ospedale San Raffaele

Azienda Ospedaliero Universitaria Pisana

Azienda Ospedaliera Sant Andrea

Istituto Nazionale Tumori Regina Elena

Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino

Ospedale di Circolo e Fondazione Macchi

Ospedale San Bortolo

Aso Co.,Ltd Iizuka Hospital

St.Marianna University Hospital

Nara Medical University Hospital

Kimitsu Chuo Hospital

Nagasaki University Hospital

JOHAS Osaka Rosai Hospital

Toranomon Hospital

Toyama University Hospital

Fujita Health University Hospital

University of Tsukuba Hospital

Yokohama City University Medical Center

Inje University Haeundae Paik Hospital

Kyungpook National University Chilgok Hospital

Keimyung University Dongsan Hospital

National Cancer Center

Chonnam National University Hospital

Seoul National University Hospital

Severance Hospital

Gangnam Severance Hospital

The Catholic University of Korea, Seoul St. Mary's Hospital

Pusan National University Yangsan Hospital

NKI-AVL, Amsterdam

Catharina Ziekenhuis

Canisius-Wilhelmina Ziekenhuis

The Julius Center - Utrecht Science Park - Stratenum

Hospital Garcia de Orta

Chbv - Hosp. Infante D. Pedro

Overall CR rate is defined as the percentage of participants achieving a CR at any time post-treatment. It will be measured by determining the percentage of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point.

DFS will be measured as the time from the date of first dose of study treatment to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first.

DOR is defined from the date of first CR achieved to the date of first evidence of recurrence or progression or death (whichever is earlier) for participants who achieve a CR.

OS, defined as the time from the date of first dose of study treatment to death; if a participant has not died at the time of analysis, the participant will be censored at the date last known alive.

Concentrations of gemcitabine and its metabolite dFdU in urine and plasma will be assessed.

Serum concentration of anti-cetrelimab antibodies will be assessed using a validated immunoassay for anti-drug antibody (ADA) analysis.

Number of participants with anti-cetrelimab antibodies will be reported.

EORTC QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. It incorporates 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 symptom scales (fatigue, pain, and nausea or vomiting), and a global health status or HRQoL scale. Ratings for each item range from 1 (not at all) to 4 (very much).

EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with superficial (non-muscle-invasive) bladder cancer. The questionnaire is designed to supplement the QLQ-C30 and incorporates 6 multi-item scales and 5 single items. Ratings for each item range from 1 (not at all) to 4 (very much).

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity grades ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guérin Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy

Trials at a glance

Trials at a glance

A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guérin Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy

Outcome measures

Primary outcome measures

Secondary outcome measures