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)
Purpose
A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to pembrolizumab plus chemotherapy in cisplatin eligible patients.
Condition
- Bladder Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- Double-blind
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Pembrolizumab + Gemcitabine + Cisplatin + Surgery |
Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab. |
|
|
Placebo Comparator Placebo + Gemcitabine + Cisplatin + Surgery |
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. |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Merck Sharp & Dohme LLC