Clinical Trials Register

Summary
EudraCT Number:	2020-002646-16
Sponsor's Protocol Code Number:	17000139BLC2001
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2020-12-07
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2020-002646-16

A.3

Full title of the trial

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-Guerin (BCG) who are Ineligible for or Elected Not to Undergo Radical Cystectomy

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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 Unresponsive to Intravesical Bacillus Calmette-Guerin who are Ineligible for or Elected Not to Undergo Radical Cystectomy

A.3.2

Name or abbreviated title of the trial where available

SunRISe-1

A.4.1

Sponsor's protocol code number

17000139BLC2001

A.5.4

Other Identifiers

Name:

IND

Number:

149505

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen-Cilag International NV
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Janssen Research & Development LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 AG
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3171524 21 66
B.5.5	Fax number	+3171524 21 10
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	TAR-200
D.3.2	Product code	JNJ-17000139
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravesical use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	gemcitabine hydrochloride
D.3.9.1	CAS number	122111-03-9
D.3.9.2	Current sponsor code	JNJ-17000139-AAC
D.3.9.3	Other descriptive name	GEMCITABINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02324MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	225
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Cetrelimab
D.3.2	Product code	JNJ-63723283
D.3.4	Pharmaceutical form	Lyophilisate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not assigned
D.3.9.2	Current sponsor code	JNJ-63723283
D.3.9.3	Other descriptive name	CNTO 8470, anti-PD-1
D.3.9.4	EV Substance Code	SUB193853
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	240
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	monoclonal antibody

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Non-Muscle-Invasive Urothelial Carcinoma (NMIBC) of the Bladder

E.1.1.1

Medical condition in easily understood language

Bladder cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10046714
E.1.2	Term	Urothelial carcinoma bladder
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10046720
E.1.2	Term	Urothelial carcinoma bladder stage II
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10046721
E.1.2	Term	Urothelial carcinoma bladder stage III
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10046722
E.1.2	Term	Urothelial carcinoma bladder stage IV
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

- To evaluate the durability of CR in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with CIS (with or without concomitant Ta or T1 papillary disease) who achieve a CR.
- To determine the overall survival (OS) in all participants.
- To evaluate the pharmacokinetics (PK) of gemcitabine and major metabolite 2’,2’-difluorodeoxyuridine (dFdU) in urine and plasma in TAR-200 in
combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2).
- To evaluate the PK and immunogenicity of cetrelimab in serum in combination with TAR-200 (Cohort 1), or cetrelimab alone (Cohort 3).
- To evaluate health-related quality of life (HRQoL) in all participants.
- To assess the safety and tolerability of participants receiving TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥18 years male or female (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
2. Histologically confirmed diagnosis of high-risk, non-muscle invasive urothelial carcinoma in situ (CIS; Tis) [AJCC, 2017], with or without papillary disease (T1, high-grade Ta) within 12 months of completion of adequate BCG therapy.
3. Visible papillary disease must be fully resected (absent) prior to randomization (residual CIS acceptable) and documented at screening cystoscopy.
4. Participants must be willing to undergo all study procedures (e.g., multiple cystoscopies from Screening through the end of study and TURBT/bladder biopsy for assessment of recurrence/progression).
5. Participants must be ineligible for or have elected not to undergo radical cystectomy.
6. BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as a minimum of 5 of 6 doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or 2 of 6 doses of a second induction course.
7. All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to CTCAE version 5.0 Grade <2 prior to screening.
8. Participants must sign the informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study and agree to store samples when applicable.
9. Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2.
10. Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment.
11. Adequate bone marrow, liver, and renal function
12. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies.
13. A woman of childbearing potential must have a negative pregnancy test (β-hCG) (serum)
within the Screening period.

E.4

Principal exclusion criteria

1. Histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and/or Stage IV).
2. Concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.
3. Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study.
4. 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.
5. Evidence of bladder perforation during diagnostic cystoscopy.
6. Bladder post-void residual (PVR) volume > 350mL at Screening after second voided urine.
7. Participants should not have a history of acute ischemic heart disease within 30 days of cohort assignment, or history of uncontrolled cardiovascular disease.
8. A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 mL.
9. Participants with an active, known or suspected autoimmune disease. Participants with autoimmune disorders not requiring systemic treatment (e.g. skin conditions such as vitiligo, psoriasis, alopecia) or conditions requiring hormonal replacement therapies such as type 1 diabetes mellitus or hypothyroidism are permitted to enroll.
10. Received a live virus vaccine within 30 days of planned start of study treatment.
11. Active infection requiring systemic therapy.
12. Has had an allogeneic tissue/solid organ transplant.
13. Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to screening.
14. Indwelling catheters are not permitted; however, intermittent catheterization is acceptable.
15. Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/Transurethral Resection of Bladder Tumor (TURBT) to starting study treatment. Immediate post-operative intravesical chemotherapy prior to signing the ICF is allowed per local standard of care.
16. Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor.
17. Participants with a history of Grade ≥3 toxic effects when using anti-TNF or anti-IL-6 agents are excluded.
18. Not recovered from toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration).
19. Participants who require immunosuppressive medications including but not limited to systemic corticosteroid at doses >10 mg/day of prednisone or its equivalence, methotrexate, cyclosporine, azathioprine, and TNF α blockers.
20. Participants must not have clinically significant liver disease that precludes participant treatment regimens prescribed on the study.
21. Known human immunodeficiency virus (HIV) infection, unless the participant has been on a stable anti-retroviral therapy regimen for the last 6 months or more and has had no opportunistic infections and a CD4 count of >350 in the last 6 months.
22. Known active hepatitis B or C infection.
23. Concurrent urinary tract infection (UTI), defined as a symptomatic infection with a positive urine culture with a bacterial count of ≥105 colony forming units (CFU)/mL in urine voided from women, or >104 CFU/mL in urine voided from men, or in straight-catheter urine from women.
24. Participants with a history of allergy to protein-based therapies and participants with a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anemia) are excluded.
25. Known hypersensitivity to any component of the drug formulation for cetrelimab.
26. Known hypersensitivity to gemcitabine (or other drug excipients) or chemically-related drugs.
27. Known hypersensitivity to the device constituent or the (TAR-200) Urinary Placement
Catheter materials.
28. Evidence of interstitial lung disease or active non-infectious pneumonitis
29. Participants must not have active tuberculosis.
30. Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions.
31. Major surgery within 4 weeks before screening (TURBT is not considered major
surgery).
32. Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the participants (e.g., compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
33. The participant is unable to comply with the requirements of this protocol, including
any factors that are likely to affect the participant’s return for scheduled visits and
follow-up.

E.5 End points

E.5.1

Primary end point(s)

Overall CR rate will be measured by determining the proportion of participants without presence of high-grade disease using results from cystoscopy
and centrally read urine cytology at any time point.

E.5.1.1

Timepoint(s) of evaluation of this end point

date of disease progression/death

E.5.2

Secondary end point(s)

- Durability of response.
- OS
- Gemcitabine and dFdU concentrations in urine and plasma.
- Serum concentration and incidence of anti-cetrelimab antibodies.
- Change from baseline and time to symptom deterioration in EORTC
QLQ-C30 and EORTC QLQ-NMIBC24.
- Frequency and grade of adverse events (AEs) (according to Common
Terminology Criteria for Adverse Events [CTCAE] version 5).
- Laboratory abnormalities: CTCAE grades comparing baseline to the
worst post-baseline value; other safety data, such as vital signs, will be
considered as appropriate.
- assessment of product quality compliants.

E.5.2.1

Timepoint(s) of evaluation of this end point

- 12 months after achievement of a CR
- date of disease progression/death
- Week 24 and 48

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

113

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

European Union

Japan

Korea, Republic of

Russian Federation

Turkey

Ukraine

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The study is considered completed with the last follow-up overall survival assessment for the last participant participating in the study, or 5 years after the last participant is randomized. The final data from the study site will be sent to the sponsor (or designee) after completion of the final
participant’s survival assessment at that study site, in the time frame specified in the Clinical Trial Agreement.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

In case the subject is unable to read or write, witness signature will be required.

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

200

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-04-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-08

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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