A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to pembrolizumab plus chemotherapy in cisplatin eligible patients.

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

7 Jun 2019 → 19 May 2026

Decision date (initial)

2024-01-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501970-20-01

EudraCT number

2018-003808-39

WHO UTN

U1111-1282-6279

ClinicalTrials.gov

NCT03924856

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To compare event-free survival (EFS) between Arm A (perioperative pembrolizumab + neoadjuvant chemotherapy + Radical Cystectomy [RC] + Pelvic Lymph Node Dissection [PLND]) and Arm B (perioperative placebo + neoadjuvant chemotherapy + RC + PLND).

Secondary objectives 6

1. To compare pathologic complete response (pCR) rates obtained in Arm A (preoperative pembrolizumab + neoadjuvant chemotherapy + RC + PLND) and Arm B (preoperative placebo + neoadjuvant chemotherapy + RC + PLND).
2. To compare the overall survival (OS) between Arm A (perioperative pembrolizumab + neoadjuvant chemotherapy + RC + PLND) and Arm B (perioperative placebo + neoadjuvant chemotherapy + RC + PLND).
3. To assess disease-free survival (DFS) in participants from Arm A (perioperative pembrolizumab + neoadjuvant chemotherapy + RC + PLND) and Arm B (perioperative placebo + neoadjuvant chemotherapy + RC + PLND).
4. To compare the rate of pathologic downstaging (pDS) between Arm A (preoperative pembrolizumab + neoadjuvant chemotherapy + RC + PLND) and Arm B (preoperative placebo + neoadjuvant chemotherapy + RC + PLND).
5. To evaluate the safety and tolerability of pembrolizumab + chemotherapy + RC + PLND.
6. To evaluate changes in patient reported outcomes from baseline and time to deterioration (TTD) using the Functional Assessment of Cancer Therapy-Bladder-Cystectomy (FACT-BI-Cys instrument and European Quality of Life Questionnaire (EQ-5D-5L).

Conditions and MedDRA coding

Cis-eligible Muscle-invasive bladder cancer.

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology.
2. Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) of the chest/abdomen/pelvis.
3. Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND).
4. Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
5. Have adequate organ function.
6. Male and female participants are eligible to participate if they agree to the contraception use as per study protocol.

Exclusion criteria 10

1. Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions.
2. Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
3. Has ≥N2 disease or metastatic disease (M1) as identified by imaging.
4. Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol.
5. Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder.
6. Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.
7. Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention.
8. Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection, Hepatitis B infection or known active Hepatitis C infection.
9. Has a known psychiatric or substance abuse disorder.
10. Has had an allogenic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-Free Survival (EFS)

Secondary endpoints 13

1. Pathologic Complete Response (pCR) Rate
2. Overall Survival (OS)
3. Disease-Free Survival (DFS)
4. Pathologic Downstaging (pDS) Rate
5. Number of Participants Who Experienced an Adverse Event (AE)
6. Number of Participants Who Discontinued Study Treatment Due to an AE
7. Number of Participants Who Experienced Perioperative Complications
8. Change in Patient-Reported Outcomes from Baseline in the Total Score of Functional Assessment of Cancer Therapy – General (FACT-G)
9. Change in Patient-Reported Outcomes from Baseline in the Total Score of FACT-Bladder- (FACT-BI-Cys)
10. Change in Patient-Reported Outcomes from Baseline in FACT-BI-Cys-Trial Outcome Index (TOI)
11. Change in Patient-Reported Outcomes from Baseline in European Quality of Life Questionnaire (EQ-5D-5L) Visual Analog Score (VAS)
12. Time to Deterioration (TTD) in the Total Score of FACT-G
13. TTD in EQ-5D-5L VAS

Investigational products

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

Test 1

Placebo 1

Auxiliary 2

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

Ritesh Kataria

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Ritesh Kataria

Third parties 7

Locations

10 EU/EEA countries · 56 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 80 files

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

Application history

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