Perioperative Pembrolizumab (MK-3475) Plus Neoadjuvant Chemotherapy Versus Perioperative Placebo Plus Neoadjuvant Chemotherapy for Cisplatin-eligible Muscle-invasive Bladder Cancer (MIBC) (MK-3475-866/KEYNOTE-866)

Phase 3Active Not RecruitingNCT03924856

Merck Sharp & Dohme LLC907 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

907

Conditions

Bladder Cancer

Interventions

PembrolizumabDRUG

Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle

GemcitabineDRUG

Gemcitabine 1000 mg/m\^2, IV infusion on Days 1 and 8 of each 21-day cycle

CisplatinDRUG

Cisplatin 70 mg/m\^2, IV infusion on Day 1 of each 21-day cycle

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology. * 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. * Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND). * Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Have adequate organ function. * Male and female participants are eligible to participate if they agree to the contraception use as per study protocol. Exclusion Criteria: * Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions. * 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). * Has ≥N2 disease or metastatic disease (M1) as identified by imaging. * Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol. * Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder. * Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC. * Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention. * 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. * Has a known psychiatric or substance abuse disorder. * Has had an allogenic tissue/solid organ transplant.

Locations (175)

Outcomes

Primary Outcomes

Event-Free Survival (EFS)

EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery; failure to undergo RC surgery in participants with residual disease and any radiographical disease present; gross residual disease left behind at the time of surgery; local or distant recurrence based on investigator assessments and/or biopsy, or death due to any cause.

Time frame: Up to approximately 60 months

Secondary Outcomes

Pathologic Complete Response (pCR) Rate

pCR rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as assessed by blinded independent central review (BICR).

Time frame: Up to approximately 72 months

Overall Survival (OS)

Overall survival is defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 72 months

Disease-Free Survival (DFS)

DFS is defined as the time from post-surgery baseline scan until the first occurrence of either local or distant recurrence as assessed by investigator by CT or MRI and/or computerized tomography (CT) or magnetic resonance imaging (MRI) and or biopsy or death from any cause.

Time frame: From approximately 20 weeks up to approximately 72 months

Pathologic Downstaging (pDS) Rate

pDS rate is defined as the percentage of participants having pDS. pDS is defined as participants with a tumor classification of \<pT2 (includes pT0, pTis, pTa, pT1) and N0 in examined tissue from RC plus PLND as assessed by BICR.

Time frame: Up to approximately 72 months

Number of Participants Who Experienced an Adverse Event (AE)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.

PlaceboDRUG

Placebo to pembrolizumab by IV infusion, given on Day 1 of each 21-day cycle

Scripps MD Anderson ( Site 0010)

La Jolla, California, United States

Providence Saint John's Health Center ( Site 0075)

Santa Monica, California, United States

Georgetown University Medical Center ( Site 0022)

Washington D.C., District of Columbia, United States

AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlando ( Site 0005)

Orlando, Florida, United States

Parkview Cancer Institute ( Site 0077)

Fort Wayne, Indiana, United States

Indiana University Melvin and Bren Simon Cancer Center ( Site 0004)

Indianapolis, Indiana, United States

Ochsner Medical Center ( Site 0049)

New Orleans, Louisiana, United States

New England Cancer Specialists ( Site 0070)

Scarborough, Maine, United States

UMass Memorial Medical Center ( Site 0051)

Worcester, Massachusetts, United States

Henry Ford Hospital ( Site 0039)

Detroit, Michigan, United States

...and 165 more locations

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Time frame: Up to approximately 72 months

Number of Participants Who Discontinued Study Treatment Due to an AE

Time frame: Up to approximately 12 months

Number of Participants Who Experienced Perioperative Complications

Time frame: Up to approximately 12 months

Change in Patient-Reported Outcomes from Baseline in Total Score of Functional Assessment of Cancer Therapy - General (FACT-G)

Time frame: Baseline, Up to approximately 72 months

Change in Patient-Reported Outcomes from Baseline in Total Score of FACT-Bladder- (FACT-BI-Cys)

Total Score of FACT BI-Cys is the sum of FACT-G total score and FACT-Bl-Cys score. FACT-Bl-Cys contains 17 items on the bowel, bladder, and sexual symptoms following cystectomy. The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 to 4, with higher scores indicating higher HRQoL. The total score of FACT-Bl-Cys can range from 0 to 168.

Time frame: Baseline, Up to approximately 72 months

Change in Patient-Reported Outcomes from Baseline in FACT-BI-Cys-Trial Outcome Index (TOI)

FACT-Bl-Cys Trial Outcome Index (TOI) is the sum of FACT-G PWB score, FWB score, and FACT-Bl-Cys score. FACT-Bl-Cys contains 17 items on the bowel, bladder, and sexual symptoms following cystectomy. The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 to 4, with higher scores indicating higher HRQoL. The total score of FACT-Bl-Cys TOI can range from 0 to 116.

Time frame: Baseline, Up to approximately 72 months

Change in Patient-Reported Outcomes from Baseline in EuroQol Five-Dimensional Questionnaire (EQ-5D-5L) Visual Analog Score (VAS)

The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. In the EQ-5D-5L VAS, the participant rates his or her general state of health at the time of the assessment on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

Time frame: Baseline, Up to approximately 72 months

Time to Deterioration (TTD) in the Total Score of FACT-G

The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0-4, with higher scores indicating higher HRQoL. TTD is defined as the time from baseline to the first onset of patient-reported outcomes (PRO) deterioration. For the FACT-G questionnaire, deteriorations are defined as a decrease of 7 points or more (out of 108) from baseline in total score.

Time frame: Up to approximately 72 months

TTD in EQ-5D-5L VAS

The EQ-5D-5L is a standardized instrument for use as a measure of health outcome and includes 5 health state dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In the EQ-5D-5L VAS, the participant rates his or her general state of health at the time of the assessment on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. TTD is defined as the time from baseline to the first onset of PRO deterioration. For the EQ 5D-5L, deterioration is defined as a decrease of 7 points or more from baseline in the VAS.

Time frame: Up to approximately 72 months