Study of Pemetrexed+Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in Participants With First Line Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-3475-189/KEYNOTE-189)-Japan Extension Study

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Non-Small-Cell Lung Carcinoma

Treatments: Biological: Pembrolizumab 200 mg; Dietary Supplement: Vitamin B12 1000 μg; Drug: Dexamethasone 4 mg; Drug: Pemetrexed; Dietary Supplement: Folic acid 350-1000 μg; Drug: Cisplatin; Drug: Carboplatin; Drug: Saline solution

Study type: Interventional

Funder types: Industry

Identifiers

NCT03950674

163421 (Registry Identifier)

MK-3475-189 (Other Identifier)

3475-189 Japan Extension

KEYNOTE-189 (Other Identifier)

Details and patient eligibility

About

This is a Japan Extension Study of Global Study MK-3475-189 (NCT02578680). This is an efficacy and safety study of pembrolizumab (MK-3475) combined with pemetrexed/platinum chemotherapy versus pemetrexed/platinum chemotherapy alone in adult Japanese participants with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease. Participants will be randomly assigned to receive pembrolizumab combined with pemetrexed/platinum (Investigators choice of cisplatin or carboplatin), OR pemetrexed/platinum (Investigators choice of cisplatin or carboplatin).

With Amendment 11 (effective date 31-Jan-2022), once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.

The primary hypothesis is that pembrolizumab in combination with pemetrexed/platinum chemotherapy prolongs Progression-Free Survival (PFS) and Overall Survival (OS) compared to pemetrexed/platinum chemotherapy alone.

Full description

The MK-3475-189-Japan Extension Study will be identical to the global study (e.g. inclusion and exclusion criteria, study primary and secondary outcome measures and study procedures).

The MK-3475-189-Japanese Extension Study enrolled a total of 30 participants and the analyses included 10 participants (pembrolizumab =4; control = 6) that had been previously enrolled in the MK-3475-189 global study (NCT02578680), resulting in a total of 40 participants.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV nonsquamous NSCLC.
• Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated.
• Has measurable disease.
• Has not received prior systemic treatment for their advanced/metastatic NSCLC.
• Can provide tumor tissue.
• Has a life expectancy of at least 3 months.
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
• Has adequate organ function
• If female of childbearing potential, is willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents.
• If male with a female partner(s) of child-bearing potential, must agree to use adequate contraception starting with the first dose of study medication through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents.

Exclusion criteria

• Has predominantly squamous cell histology NSCLC.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab.
• Before the first dose of study medication: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease, b) Has received antineoplastic biological therapy (e.g. erlotinib, crizotinib, cetuximab), c) Had major surgery (<3 weeks prior to first dose)
• Received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study medication.
• Completed palliative radiotherapy within 7 days of the first dose of study medication.
• Is expected to require any other form of antineoplastic therapy while on study.
• Received a live-virus vaccination within 30 days of planned start of study medication.
• Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, peritoneal carcinomatosis.
• Known history of prior malignancy except if participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy, except for successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
• Known sensitivity to any component of cisplatin, carboplatin or pemetrexed.
• Has active autoimmune disease that has required systemic treatment in past 2 years.
• Is on chronic systemic steroids.
• Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
• Is unable or unwilling to take folic acid or vitamin B12 supplementation.
• Had prior treatment with any other anti-programmed cell death-1 (PD-1), or PD-ligand 1 (PD-L1) or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms. Has participated in any other pembrolizumab study and has been treated with pembrolizumab.
• Has an active infection requiring therapy.
• Has known history of Human Immunodeficiency Virus (HIV).
• Has known active Hepatitis B or C.
• Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
• Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
• Has symptomatic ascites or pleural effusion.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 2 patient groups

Pembrolizumab with Pemetrexed and Platinum Chemotherapy Followed by Pembrolizumab and Pemetrexed

Experimental group

Description:

Participants receive pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m\^2 IV Q3W until progression. Participants who receive pembrolizumab 200 mg IV Q3W for up to 2 years, but experience disease progression, are eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year.

Treatment:

Drug: Carboplatin

Drug: Cisplatin

Dietary Supplement: Folic acid 350-1000 μg

Drug: Pemetrexed

Drug: Dexamethasone 4 mg

Dietary Supplement: Vitamin B12 1000 μg

Biological: Pembrolizumab 200 mg

Placebo with Pemetrexed and Platinum Chemotherapy Followed by Placebo and Pemetrexed

Active Comparator group

Description:

Participants receive saline placebo IV PLUS pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin AUC 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by saline placebo IV PLUS pemetrexed 500 mg/m\^2 IV Q3W until progression. Participants who receive saline placebo, but experience disease progression, can switch over to pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to 2 years. The participants who switch over to pembrolizumab 200 mg IV Q3W, but experience disease progression, are eligible to receive a second course of pembrolizumab monotherapy 200 mg IV Q3W, at the investigator's discretion, for up to another year.

Treatment:

Drug: Saline solution

Drug: Carboplatin

Drug: Cisplatin

Dietary Supplement: Folic acid 350-1000 μg

Drug: Pemetrexed

Drug: Dexamethasone 4 mg

Dietary Supplement: Vitamin B12 1000 μg