Pembrolizumab (MK-3475) and Pembrolizumab in combination with other agents in High Risk Non-muscle Invasive Bladder Cancer (NMIBC) Patients Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy

Phase 1

• Conditions: on-Muscle Invasive Bladder Cancer (NMIBC); MedDRA version: 20.0Level: PTClassification code 10005003Term: Bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-004026-17-SE
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-11-27
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

1. Have a histologically-confirmed diagnosis of high risk non-muscleinvasive
(T1, High Grade Ta and/or CIS) transitional cell carcinoma of
the bladder.
2. In subjects who have papillary tumors (Ta and T1), a complete TURBT
must have been performed, as characterized by:
-Attainment of a visually complete resection of all papillary tumors (Ta and T1)
-Residual CIS not amenable to complete resection is allowed
-The most recent cystoscopy/TURBT must have been performed within 12 weeks of randomization
-For Cohort C: subjects with T1 disease should have undergone a restaging TURBT procedure within 12 weeks prior to randomization to confirm complete resection.
3. Have been treated with adequate BCG therapy and have developed
high risk NMIBC that is unresponsive to BCG therapy.
4. Have elected not to undergo, or are considered ineligible for radical
cystectomy, as determined by the treating surgeon.
5. Have provided tissue for biomarker analysis from the most recent
cystoscopy/TURBT procedures from which tumor sample is available.
6. Have a performance status of 0, 1 or 2 on the Eastern Cooperative
Oncology Group (ECOG) Performance Scale. (Max of 5% ECOG of 2.) (for cohorts A and B only)
7. Have adequate organ function.
8. A female participant is eligible if not pregnant or breastfeeding, and at least one of the following applies:
- Is not a WOCBP; or
- Is a WOCBP and using a contraceptive method as described in the
protocol. A WOCBP must have a negative pregnancy test as described in
the protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 106
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 214

Exclusion Criteria

1 . Has centrally-assessed muscle invasive (i.e. T2, T3, T4) locally advanced nonresectable
or metastatic urothelial carcinoma.
2 . Has centrally-assessed concurrent extra-vesical (i.e. urethra, ureter or renal pelvis)
non-muscle invasive transitional cell carcinoma of the urothelium.
3 . Is currently participating and receiving study therapy or has
participated in a study of an investigational agent and received study
therapy or used an investigational device within 4 weeks of the first
dose of treatment.
4 . Has undergone any intervening intravesical chemotherapy or
immunotherapy from the time of the most recent cystoscopy/TURBT to
starting trial treatment.
5. Has had prior chemotherapy, targeted small molecule therapy, or
radiation therapy within 2 weeks prior to Cycle 1, Day 1 or who has not
recovered (ie, = Grade 1 or at baseline) from adverse events due to a previously administered agent.
6. Has a known additional malignancy that has had progression or has required active treatment in the last three years
7. Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks
before randomization/study allocation for Cohort C.
8. Has severe hypersensitivity to pembrolizumab (all cohorts), MK-7684A (Cohort C arm 1), MK-4280A (Cohort C Arm 2), and/or any of their excipients.
9. Has an active autoimmune disease that has required systemic treatment in past 2 years
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone
equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study intervention. The use of
physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
11. Has a history of (non-infectious) pneumonitis/or interstitial lung disease that required steroids or has current pneumonitis.
12. Has an active infection requiring systemic therapy, including active or intractable UTI in the last month.
13. Has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the trial,
interfere with the subject's participation, or is not in the best interest of the subject to participate, in the opinion of the investigator.
14. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the
requirements of the trial.
15. Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit through
120 days after the last dose of trial treatment.
16. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL2 agent, or with an agent directed to another co-inhibitory T-cell receptor
(e.g. CTLA-4, OX-40, CD137).
17. Has received previous treatment with another agent targeting the TIGIT and/or LAG3 receptor pathway (Cohort C only).
18. Has a known history of Human Immunodeficiency Virus (HIV) (HIV- 1/2 antibodies).
19. Has known active Hepatitis B or Hepatitis C.
20. Has received a live virus vaccine within 30 days of planned start of trial treatment.
21. Has had an allogeneic tissue/solid organ transplant.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified