A Study of Pembrolizumab in Combination With Cisplatin an... | NCT04153565

NCT04153565

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
MK-3475-A17	Other Identifier	Merck Protocol Number
195054	Registry Identifier	JAPIC-CTI

Status Module

Label	Type	Description	Intervention Names
Pembrolizumab + Cisplatin + Pemetrexed	Experimental	Pembrolizumab 200 mg IV every 3 weeks (Q3W) in combination with Cisplatin 75 mg/m^2 IV, and Pemetrexed 500 mg/m^2 IV for 4-6 cycles followed by monotherapy of Pembrolizumab up to 35 cycles from the first dose of the study in treatment phase (approximately 2 years).	Drug: Pembrolizumab Drug: Pemetrexed Drug: Cisplatin

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Drug	Participants will receive Pembrolizumab 200 mg IV every 3 weeks (Q3W) until disease progression, or until participant has received 35 administrations of Pembrolizumab (approximately 2 years).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 1, Per Common Terminology Criteria for Adverse Events (AEs), Version 5.0 (CTCAE)	DLTs were assessed during Cycle 1 (21 days) and defined as any of the following, if considered by investigator to be related to any of the study interventions: Grade 4 hematologic toxicities, except neutropenia and febrile neutropenia; Grade 4 neutropenia lasting >7 days despite appropriate supportive treatment; Grade 4 febrile neutropenia only if the event considered as clinically significant by investigator and sponsor; any Grade 4 non-hematologic toxicity (except laboratory test abnormal including transient electrolyte abnormalities); any Grade 3 non-hematologic toxicity lasting >72 hours despite appropriate supportive treatment (not laboratory); and any Grade 4 laboratory test value abnormality; any Grade 3 laboratory test value abnormality lasting >7 days; delay in start of second course of more than 2 weeks (more than 35 days after the first dose) due to toxicity related to study procedures; any Grade 5 toxicity.	Up to 3 weeks (through Cycle 1 [21 days])
Number of Participants With One or More Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE.	Up to approximately 34 months
Number of Participants Discontinuing Study Treatment Due to an AE	An AE was defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE.

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the percentage of participants who have a Complete Response (CR: disappearance of target and non-target lesions and normalization of tumor markers) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions). ORR was based on modified Response Evaluation Criteria In Solid Tumors (RECIST) for Malignant Pleural Mesothelioma (MPM) as assessed by investigator.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has histologically confirmed diagnosis of advanced/unresectable malignant pleural mesothelioma (MPM)
Have at least one measurable disease, which is systemic therapy naïve, radiologically assessed by the local site investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) using imaging scanned within 28 days prior to the first dose in this study
Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
Has a life expectancy of at least 3 months
Demonstrate adequate organ function
Male participants are eligible to participate if they agree to remain abstinent or agree to use contraception unless confirmed to be azoospermic
A female participant is eligible to participate if she is not pregnant or breastfeeding, using contraceptives or is not a woman of child bearing potential (WOCBP)

Exclusion Criteria:

A WOCBP who has a positive pregnancy test within 72 hours prior to treatment allocation
Has received prior therapy with an anti-programmed cell-death 1 (anti PD-1), anti programmed cell-death ligand 1 (anti-PD-L1), or anti programmed cell-death ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
Has previously received systemic anti-cancer therapy (including investigational agents) for MPM
Participants who received (neo) adjuvant previously may be eligible, only if the last dose of chemotherapy was completed at least 6 months before registration. Such participants must have recovered from all adverse events (AEs) due to previous (neo) adjuvant therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible
Received radiation therapy to the lung that is > 30 gray (Gy) within 6 months of the first dose of trial treatment
Completed palliative radiotherapy within 7 days of the first dose of trial treatment
Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
Had a major surgery within 3 months prior to the first administration in this study
Has received a live vaccine within 30 days prior to the first dose of study drug
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has had a severe hypersensitivity reaction (≥Grade 3) to treatment a monoclonal antibody/components of the study intervention
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
Is being treated for pericardial effusion, or has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible
Has an active infection requiring systemic therapy
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Hyogo College of Medicine Hospital ( Site 0003)		Nishinomiya	Hyōgo	663-8501	Japan
Kanagawa Cancer Center ( Site 0004)

PubMed Identifier	Type	Citation	Retractions
40407381	Result	Kijima T, Kato T, Goto Y, Kuribayashi K, Mikami K, Negi Y, Murakami S, Yoshida T, Homma M, Wakana A, Noguchi K, Fujimoto N. KEYNOTE-A17: First-Line Pembrolizumab Plus Cisplatin-Pemetrexed in Japanese Participants With Advanced Pleural Mesothelioma. Cancer Sci. 2025 Aug;116(8):2208-2217. doi: 10.1111/cas.70082. Epub 2025 May 23.

Label	URL
Merck Clinical Trials Information	View source

ID	Title	Description
FG000	Pembrolizumab + Pemetrexed + Cisplatin	Participants received pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) in combination with pemetrexed 500 mg/m^2 IV and cisplatin 75 mg/m^2 IV for 4-6 cycles, followed by pembrolizumab 200 mg/m^2 IV monotherapy Q3W for up to 35 cycles from the first dose of the study treatment (approximately 2 years). Each cycle was 21 days.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Pembrolizumab + Pemetrexed + Cisplatin	Participants received pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) in combination with pemetrexed 500 mg/m^2 IV and cisplatin 75 mg/m^2 IV for 4-6 cycles, followed by pembrolizumab 200 mg/m^2 IV monotherapy Q3W for up to 35 cycles from the first dose of the study treatment (approximately 2 years). Each cycle was 21 days.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) During Cycle 1, Per Common Terminology Criteria for Adverse Events (AEs), Version 5.0 (CTCAE)	DLTs were assessed during Cycle 1 (21 days) and defined as any of the following, if considered by investigator to be related to any of the study interventions: Grade 4 hematologic toxicities, except neutropenia and febrile neutropenia; Grade 4 neutropenia lasting >7 days despite appropriate supportive treatment; Grade 4 febrile neutropenia only if the event considered as clinically significant by investigator and sponsor; any Grade 4 non-hematologic toxicity (except laboratory test abnormal including transient electrolyte abnormalities); any Grade 3 non-hematologic toxicity lasting >72 hours despite appropriate supportive treatment (not laboratory); and any Grade 4 laboratory test value abnormality; any Grade 3 laboratory test value abnormality lasting >7 days; delay in start of second course of more than 2 weeks (more than 35 days after the first dose) due to toxicity related to study procedures; any Grade 5 toxicity.	All participants who received at least 1 dose of study intervention and who met the criteria for DLT evaluability by finishing Cycle 1 without a DLT or having experienced a DLT	Posted		Count of Participants		Participants		Up to 3 weeks (through Cycle 1 [21 days])

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab + Pemetrexed + Cisplatin	Participants received pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) in combination with pemetrexed 500 mg/m^2 IV and cisplatin 75 mg/m^2 IV for 4-6 cycles, followed by pembrolizumab 200 mg/m^2 IV monotherapy Q3W for up to 35 cycles from the first dose of the study treatment (approximately 2 years). Each cycle was 21 days.

ID	Term
D000236	Adenoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Term
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574

ID	Term
D008654	Mesothelioma
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body