Pembrolizumab (MK-3475) and pembrolizumab in combination with other investigational agents in high risk NMIBC patients unresponsive to BCG

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Mar 2016 → 6 Nov 2025

Decision date (initial)

2023-07-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-502526-41-00

EudraCT number

2014-004026-17

WHO UTN

U1111-1284-7618

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Pharmacoeconomic, Safety, Efficacy, Therapy

1. To evaluate anti-tumor activity of pembrolizumab by evaluating the absence of high-risk NMIBC or progressive disease, as determined by cystoscopy, cytology, biopsy (if applicable), and radiologic imaging by central pathology and radiology review

Secondary objectives 6

1. To evaluate anti-tumor activity of pembrolizumab by CR rate of any disease
2. To evaluate anti-tumor activity of pembrolizumab by Duration of Response (DOR) of high-risk NMIBC and any disease (responders only)
3. To evaluate anti-tumor activity of pembrolizumab in PD-L1 positive subjects by CR rate of high-risk NMIBC and any disease
4. To evaluate anti-tumor activity of pembrolizumab in PD-L1 positive subjects by DOR of high-risk NMIBC and any disease (responders only)
5. To evaluate anti-tumor activity of pembrolizumab in the study population and in PD-L1 positive subjects by the following endpoints: DOR rate, progression-free survival (to worsening of grade or state or death), progression-free survival (to muscle-invasive or metastatic disease or death), and overall survival (OS)
6. To evaluate anti-tumor activity of pembrolizumab in the study population and in PD-L1 positive subjects by the following endpoints: overall DFS and 3-/6-month DFS rates of high-risk NMIBC and any disease; progression-free survival (to worsening of grade or state or death), progression-free survival (to muscle-invasive or metastatic disease or death), and OS

Conditions and MedDRA coding

Non-Muscle Invasive Bladder Cancer (NMIBC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Histologically-confirmed diagnosis of high risk non-muscle-invasive (T1, high grade Ta and / or carcinoma in situ [CIS]) transitional cell carcinoma of the bladder (mixed histology tumors allowed if transitional cell histology is predominant histology)
2. Fully resected disease at study entry (residual CIS acceptable)
3. BCG-unresponsive high risk non-muscle-invasive bladder cancer after treatment with adequate BCG therapy
4. Ineligible for radical cystectomy or refusal of radical cystectomy
5. Available tissue from a newly obtained core biopsy of a tumor lesion not previously irradiated
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
7. Adequate organ function
8. Female participants of childbearing potential have a negative urine or serum pregnancy test and must be willing to use an adequate method of contraception
9. Male participants must be willing to use an adequate method of contraception

Exclusion criteria 15

1. Centrally assessed muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and / or stage IV)
2. Centrally assessed concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium
3. Currently participating or has participated in a study of an investigational agent and received study therapy or received investigational device within 4 weeks prior to the first dose of study treatment
4. Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy / Transurethral Resection of Bladder Tumor (TURBT) to starting study treatment
5. Received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment or not recovered from adverse events due to a previously administered agent
6. Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with definitive intent (surgically or through radiation therapy) is acceptable provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score ≤7 and prostatic-specific antigen (PSA) undetectable for at least 1 year while off androgen deprivation therapy that was either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation
7. Active autoimmune disease that has required systemic treatment in the past 2 years
8. Evidence of interstitial lung disease or active non-infectious pneumonitis
9. Active infection requiring systemic therapy
10. Pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial through 120 days after the last dose of study treatment
11. 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
12. Known human immunodeficiency virus (HIV)
13. Known active Hepatitis B or C infection
14. Received a live virus vaccine within 30 days of planned start of study treatment
15. Has had an allogeneic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Cohort A: Complete Response (CR) Rate of High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC)
2. Cohort B: 12-month Disease-Free Survival (DFS) Rate of High-Risk NMIBC
3. Cohort A and B: Number of Participants Who Experience an Adverse Event (AE)
4. Cohort A and B: Number of Participants Who Discontinue Study Treatment Due to an AE

Secondary endpoints 8

1. Cohort A: CR Rate of Any Disease
2. Cohort A: CR Rate of High-Risk NMIBC in Programmed Cell Death 1 (PDL-1) Positive Participants
3. Cohort A: Duration of Response (DOR)
4. Cohort A and B: Progression-Free Survival (PFS)
5. Cohort A and B: Overall Survival (OS)
6. Cohort B: DFS Rate of Any Disease
7. Cohort B: 12-month DFS Rate of Any Disease
8. Cohort B: 12-month DFS Rate of High-Risk NMIBC in PDL-1 Positive Participants

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Hema Dave

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Hema Dave

Third parties 8

Locations

7 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

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

Documents 51 files

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

Application history

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