Description:
A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to
pembrolizumab plus chemotherapy in cisplatin eligible patients.
Title
- Brief Title: 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)
- Official Title: A Phase 3, Randomized, Double-blind Study to Evaluate Perioperative Pembrolizumab (MK-3475) + Neoadjuvant Chemotherapy Versus Perioperative Placebo + Neoadjuvant Chemotherapy in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-866)
Clinical Trial IDs
- ORG STUDY ID:
3475-866
- SECONDARY ID:
2018-003808-39
- SECONDARY ID:
MK-3475-866
- SECONDARY ID:
KEYNOTE-866
- SECONDARY ID:
194870
- NCT ID:
NCT03924856
Conditions
- Urinary Bladder Cancer, Muscle-invasive
Interventions
| Drug | Synonyms | Arms |
|---|
| Pembrolizumab | MK-3475 | Pembrolizumab + Gemcitabine + Cisplatin + Surgery |
| Gemcitabine | | Pembrolizumab + Gemcitabine + Cisplatin + Surgery |
| Cisplatin | | Pembrolizumab + Gemcitabine + Cisplatin + Surgery |
| Placebo | | Placebo + Gemcitabine + Cisplatin + Surgery |
Purpose
A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to
pembrolizumab plus chemotherapy in cisplatin eligible patients.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Pembrolizumab + Gemcitabine + Cisplatin + Surgery | Experimental | Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab. | - Pembrolizumab
- Gemcitabine
- Cisplatin
|
| Placebo + Gemcitabine + Cisplatin + Surgery | Placebo Comparator | Participants received 4 preoperative cycles of placebo to pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative placebo to pembrolizumab. | - Gemcitabine
- Cisplatin
- Placebo
|
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Pathologic Complete Response (pCR) Rate |
| Time Frame: | Up to approximately 15 Weeks (Time of surgery) |
| Safety Issue: | |
| Description: | pCR rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0pT0N0) in examined tissue from RC and PLND, as assessed by blinded independent central review (BICR). |
Secondary Outcome Measures
| Measure: | Overall Survival (OS) |
| Time Frame: | Up to approximately 71 months |
| Safety Issue: | |
| Description: | Overall survival is defined as the time from randomization to death due to any cause. |
| Measure: | Disease-Free Survival (DFS) |
| Time Frame: | From approximately 20 weeks up to approximately 71 months |
| Safety Issue: | |
| Description: | DFS is defined as the time from post-surgery baseline scan until the first occurrence of either local or distant recurrence as assessed by CT or MRI (BICR) and/or computerized tomography (CT) or magnetic resonance imaging (MRI) by BICR and or biopsy or death from any cause. |
| Measure: | Pathologic Downstaging (pDS) Rate |
| Time Frame: | Up to approximately 15 Weeks (Time of surgery) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Number of Participants Who Experienced an Adverse Event (AE) |
| Time Frame: | Up to approximately 71 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Number of Participants Who Discontinued Study Treatment Due to an AE |
| Time Frame: | Up to approximately 12 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Number of Participants Who Experienced Perioperative Complications |
| Time Frame: | Up to approximately 12 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 71 months |
| Safety Issue: | |
| Description: | 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 can range from 0 to 108. |
| Measure: | Change in Patient-Reported Outcomes from Baseline in Total Score of FACT-Bladder- (FACT-BI-Cys) |
| Time Frame: | Baseline, Up to approximately 71 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Change in Patient-Reported Outcomes from Baseline in FACT-BI-Cys-Trial Outcome Index (TOI) |
| Time Frame: | Baseline, Up to approximately 71 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Change in Patient-Reported Outcomes from Baseline in EuroQol Five-Dimensional Questionnaire (EQ-5D-5L) Visual Analog Score (VAS) |
| Time Frame: | Baseline, Up to approximately 71 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Time to Deterioration (TTD) in the Total Score of FACT-G |
| Time Frame: | Up to approximately 71 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | TTD in EQ-5D-5L VAS |
| Time Frame: | Up to approximately 71 months |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Merck Sharp & Dohme Corp. |
Trial Keywords
- Programmed Cell Death-1 (PD1, PD-1)
- Programmed Death-Ligand 1 (PDL1, PD-L1)
- Pembrolizumab (MK-3475)
- Chemotherapy
Last Updated
August 23, 2021
