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)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 3

Conditions: Bladder Cancer

Treatments: Drug: Gemcitabine; Drug: Placebo; Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND]); Drug: Pembrolizumab; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03924856

2080224790 (Registry Identifier)

2022-501970-20-00 (Other Identifier)

2018-003808-39 (EudraCT Number)

3475-866

MK-3475-866 (Other Identifier)

194870 (Registry Identifier)

KEYNOTE-866 (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 907 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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907 participants in 2 patient groups, including a placebo group

Pembrolizumab + Gemcitabine + Cisplatin + Surgery

Experimental group

Description:

Participants received 4 preoperative cycles of pembrolizumab PLUS gemcitabine PLUS cisplatin, followed by surgery, followed by up to 13 cycles of postoperative pembrolizumab.

Treatment:

Drug: Cisplatin

Drug: Pembrolizumab

Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])

Drug: Gemcitabine

Placebo + Gemcitabine + Cisplatin + Surgery

Placebo Comparator group

Description:

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.

Treatment:

Drug: Cisplatin

Procedure: Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])

Drug: Placebo

Drug: Gemcitabine