Pembrolizumab (MK-3475) 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-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-20
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 260

Inclusion Criteria

1.Have a histologically-confirmed diagnosis of high risk non-muscle-invasive (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 transurethral resection is acceptable
- The most recent cystoscopy / TURBT must have been performed within 12 weeks of the first dose of trial treatment
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.)
7.Demonstrate adequate organ function.
8.Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication and be willing to use contraception in accordance with 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 86
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 174

Exclusion Criteria

1.Has muscle invasive (i.e. T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma.
2.Has 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 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 (i.e., <= Grade 1 or at baseline) from adverse events due to a previously administered agent.
6.Has a known additional malignancy that is progressing or requires active treatment.
7.Has an active autoimmune disease that has required systemic treatment in past 2 years.
8 . Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned first dose of the study. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
9. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
10.Has an active infection requiring systemic therapy, including active or intractable urinary tract infection (UTI) in the last month.
11.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.
12.Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137).
13.Has a known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
14.Has known active Hepatitis B or Hepatitis C.
15.Has received a live virus vaccine within 30 days of planned start of trial treatment
16. Has had an allogeneic tissue/solid organ transplant.

Study & Design

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