A Phase 2, Open-Label, Multi-Center, Randomized Study of TAR-200 in Combination with Cetrelimab and Cetrelimab Alone in Participants with Muscle-Invasive Urothelial Carcinoma of the Bladder who are Scheduled for Radical Cystectomy and are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Jan 2022 → 31 Mar 2026

Decision date (initial)

2024-05-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Janssen Research & Development LLC

External identifiers

EU CT number

2023-507189-17-00

EudraCT number

2020-005565-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Pharmacokinetic, Pharmacodynamic

To determine the anti-tumor effects of TAR 200 + Cetrelimab (Cohort 1) and Cetrelimab alone (Cohort 2)

Secondary objectives 1

1. To evaluate the safety and tolerability of up to 4 dosing cycles of TAR200 + cetrelimab (Cohort 1) and cetrelimab (Cohort 2) alone prior to RC • To determine the recurrence-free survival (RFS) in participants receiving TAR-200 + cetrelimab (Cohort 1) and cetrelimab alone (Cohort 2)

Conditions and MedDRA coding

Muscle-Invasive Urothelial Carcinoma of the Bladder

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu URL: https://www.janssen.com/clinical-trials/transparency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. ≥18 years (or the legal age of consent where the study takes place)
2. 2. Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma (AJCC 2017) of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial predominance
3. 3. Participants with no residual tumor, or intravesical tumor size of ≤3 cm following TURBT are eligible; debulking TURBT for any residual disease is encouraged but not mandated. Participants with persistent tumors >3 cm at screening must undergo a second debulking, re-staging TURBT Participants will be ineligible if any individual tumor is >3 cm after debulking TURBT
4. 4. Deemed eligible for and willing to undergo RC by the attending urologist
5. 5. Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1
6. 6. Thyroid function tests within normal range or stable on hormone supplementation per Investigator assessment
7. 7. Adequate bone marrow, liver, and renal function (refer to study protocol for details)
8. 8.Participants must refuse cisplatin-based combination chemotherapy (and understand the risk and benefits of doing so) or be deemed ineligible for cisplatin-based chemotherapy by meeting at least one of the following criteria: • GFR <60 mL/min/1.73 m2 (assessed using the CKD-EPI equation) • Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade ≥2 audiometric hearing loss • CTCAE version 5.0 Grade ≥2 peripheral neuropathy
9. 9. Prior systemic chemotherapy for indications other than urothelial cell carcinoma of the bladder is permitted, but interval between this treatment and study enrollment must exceed 24 months. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI-CTCAE version 5.0) or baseline before administration of study treatment. Participants with toxicities attributed to prior anticancer therapy which are not expected to resolve and result in long lasting sequelae, such as peripheral neuropathy after platinum-based therapy or audiometric hearing loss, are ineligible.
10. 10. All adverse events associated with any prior surgery must have resolved to CTCAE version 5.0 Grade <2 prior to randomization
11. 11.Contraceptive use by participants should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. Investigators will advise participants on the options for banking of sperm and ova for reproductive conservation. A female participants must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment a. A female participant must be either of the following: i. Not of childbearing potential ii. Of childbearing potential and • practicing true abstinence, or have a sole partner who is vasectomized, or practicing at least 1 highly effective user independent method of contraception Participant must agree to continue the above throughout the study and for 6 months after the last dose of study treatment. Note: If a participant becomes of childbearing potential after start of the study, the participant must comply with point (ii) A female participant must also: • agrees to not donate eggs (ova, oocytes, or freeze for future use) for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study treatment • not be breastfeeding and not planning to become pregnant during the study and for at least 6 months after the last dose of study treatment b. A male participant must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 6 months after receiving the last dose of study treatment. His female partner, if of childbearing potential, must also be practicing a highly effective method of contraception. If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception. A male participant must also: • agree to not donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after the last dose of study treatment • not plan to father a child while enrolled in this study or within 6 months after the last dose of study treatment
12. 12. A female participant of childbearing potential must have a highly sensitive negative serum (β-human chorionic gonadotropin [β-hCG]) or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study, that may exceed those listed in the Schedule of Activities
13. 13. Must sign an ICF (or their legally acceptable representative must sign)

Exclusion criteria 39

1. 1. Active malignancies other than the disease being treated under study
2. 2. Must not have received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment
3. 3. Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder
4. 4. Participants must not have evidence of cT4b, or N1-3, or M1 disease based on central radiology staging within 42 days prior to randomization
5. 5. Presence of any bladder or urethral anatomic feature that, in the opinion of the Investigator, may prevent the safe placement, indwelling use, or removal of TAR-200
6. 6. Uncontrolled adrenal insufficiency
7. 7. A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4,000 mL
8. 8. History of uncontrolled cardiovascular disease
9. 9. Must not have active tuberculosis
10. 10. Criterion - deleted per Amendment 1
11. 11.Pyeloureteral tube externalized to the skin is exclusionary
12. 12. Indwelling catheters are not permitted
13. 13. Participants with an active autoimmune disease that required systemic treatment in the past 2 years
14. 14. Participants must not have clinically significant liver disease that precludes participant treatment regimens prescribed on the study
15. 15.Human immunodeficiency virus infection
16. 16.Evidence of active or chronic hepatitis B or C infection
17. 17.Concurrent urinary tract infection (UTI), that cannot be cleared with antibiotic therapy
18. 18.Criterion deleted per Amendment 2
19. 19.Evidence of interstitial lung disease or active non-infectious pneumonitis.
20. 20.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
21. 21.Participants with current acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation, and participants who have a history immune-mediated colitis
22. 22.Criterion deleted per Amendment 2
23. 23.Not recovered from adverse events due to a previously administered agent
24. 24.Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time.
25. 25.Pelvic radiotherapy administered less than 6 months prior to screening
26. 26.Received a live virus vaccine within 30 days of initiation of study treatment. Inactivated (non-live or non-replicated) vaccines approved or authorized for emergency use (eg, Coronavirus Disease 2019 [COVID19]) are allowed
27. 27.Criterion deleted per Amendment 2
28. 28.Active infection requiring systemic intravenous therapy within 14 days prior to randomization.
29. 29.Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/TURBT to starting study treatment. Immediate post-TURBT single-dose peri-operative intravesical chemotherapy is allowed per institutional guidelines in the screening phase.
30. 30.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, antiCD137, or anti cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
31. 31.Participants with a history of Grade ≥3 toxic effects when using antiTNF or anti-IL-6 agents are excluded.
32. 32.Participants still recovering from toxicity of prior anticancer therapy which was received more than 24 months prior to enrollment (except toxicities which are not clinically significant such as alopecia, skin discoloration).
33. 33.Participants who require immunosuppressive medications
34. 34.Participants with a history of allergy to protein-based therapies and participants with a history of any significant drug allergy are excluded.
35. 35.Known hypersensitivity to any study component including: a.Gemcitabine (or other drug excipients) or chemically-related drugs, b.TAR-200 device constituent materials, c.TAR-200 Urinary Placement Catheter materials, d.Cetrelimab excipients or chemically-related drugs Refer to the TAR-200 IB and cetrelimab IB for complete information on excipients
36. 36.Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment.
37. 37.Participants with evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has resolved prior to dosing.
38. 38.Bladder post-void residual (PVR) volume >350mL at screening after second voided urine.
39. 39.Participants who have not recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. pCR rate at radical cystectomy (RC)

Secondary endpoints 1

1. • Frequency and grade of AEs • Laboratory abnormalities • Recurrence-free survival (RFS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS point of Contact

Third parties 12

Locations

6 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 111 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications