Study of Pembrolizumab (MK-3475) in Participants With Advanced Non-small Cell Lung Cancer (MK-3475-025/KEYNOTE-025)

Non-small Cell Lung Cancer Clinical Trial

Official title:

An Open-label, Non-randomized, Multi-center Phase Ib Study of MK-3475 in Subjects With PD-L1 Positive Advanced Non-small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02007070
• Other study ID #: 3475-025
• Secondary ID: 142500MK-3475-02
• Status: Completed
• Phase: Phase 1
• Start date: February 28, 2014
• Est. completion date: March 31, 2017

Study information

• Verified date: April 2020
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to evaluate the safety and efficacy of pembrolizumab (MK-3475) in participants with advanced non-small cell lung cancer (NSCLC) tumors that are positive for programmed cell death ligand 1 (PD-L1): the hypothesis is that treatment with pembrolizumab will result in a clinically meaningful Overall Response Rate (ORR).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: March 31, 2017
• Est. primary completion date: July 9, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is PD-L1 positive per central laboratory review

• At least one measurable lesion

• Radiographic progression of NSCLC after treatment with a platinum-containing doublet for Stage IIIB/IV or recurrent disease

• Eastern Cooperative Oncology Group (ECOG) Performance Scale 0 or 1

• Adequate organ function

Exclusion Criteria:

• Systemic cytotoxic chemotherapy, biological therapy, or major surgery within 3 weeks of the first dose of trial treatment

• Systemic steroid therapy within 3 days prior to the first dose of trial treatment or any other form of immunosuppressive medication

• Expected to require any other form of systemic or localized antineoplastic therapy while on trial

• History of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer

• Active central nervous system (CNS) metastases and/or carcinomatous meningitis

• Active autoimmune disease or documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents

• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody

• Concurrent or past history of interstitial lung disease

• Pregnant or breast-feeding, or expecting to conceive or father children within the projected duration of the study, starting with screening visit through 120 days after the last dose of pembrolizumab

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Biological:
• Pembrolizumab
Intravenous infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strongly PD-L1 Positive Participants	On-study imaging was to be performed every 9 weeks after the first dose of study drug, or more frequently if clinically indicated. ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). The percentage of strongly PD-L1 positive participants who experienced a CR or PR is presented.	Up to 2 years
Primary	Number of Participants Experiencing Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. 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 the study drug, was also an AE. After discontinuation of study drug, each participant was monitored for a minimum of 30 days for AE monitoring (serious AEs were monitored for up to 90 days after last dose of study drug). The number of participants who experienced an AE is presented.	Up to 27 months (Up to 90 days after last dose of study drug)
Primary	Number of Participants Discontinuing Study Drug Due to AEs	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. 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 the study drug, was also an AE. The number of participants who discontinued study drug due to an AE is presented.	Up to 2 years
Secondary	Progression Free Survival (PFS) by RECIST 1.1 in Strongly PD-L1 Positive Participants	PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central radiologists' review or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm in the sum of lesions, OR the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and is reported in months. The median PFS for all strongly PD-L1 positive participants is presented.	Up to 2 years
Secondary	Duration of Response (DOR) by RECIST 1.1 in Strongly PD-L1 Positive Participants	DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed using the Kaplan-Meier method and is reported in days. The median DOR for all strongly PD-L1 positive participants with a confirmed response is presented.	Up to 2 years
Secondary	Overall Survival (OS) in Strongly PD-L1 Positive Participants	OS was defined as the time from the first day of study treatment to death due to any cause. OS is reported for all strongly PD-L1 positive participants in months	Up to 2 years
Secondary	ORR Per Immune-Related Response Criteria (irRC) in Strongly PD-L1 Positive Participants	ORR per irRC was defined as the percentage of participants in the analysis population who had a Complete Response (irCR: Complete disappearance of all tumor lesions [whether measureable or not, and no new lesions; irCR must be confirmed by repeated, consecutive assessments made no less than 4 weeks from the date first documented]) or Partial Response (irPR: Decrease in sum of the products of the two largest perpendicular diameters [SPD] of 50% or greater by a consecutive assessment at least 4 weeks after first documentation). The percentage of strongly PD-L1 positive participants who experienced an irCR or irPR is presented.	Up to 2 years
Secondary	PFS Per irRC in Strongly PD-L1 Positive Participants	PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRC or death due to any cause, whichever occurred first. Using irRC, progressive disease was defined as at least a 25% increase in SPD relative to minimum recorded tumor burden. Confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented was required. Median PFS was analyzed using the Kaplan-Meier method and is presented in months for all strongly PD-L1 positive participants.	Up to 2 years
Secondary	DOR Per irRC in Strongly PD-L1 Positive Participants	DOR was measured from the time measurement criteria were first met for irCR/irPR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). PD was defined as at least a 25% increase in SPD relative to minimum recorded tumor burden. Confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented was required. DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. DOR was analyzed using the Kaplan-Meier method, is reported in days and is presented for all strongly PD-L1 positive participants who experienced an irCR or irPR.	Up to 2 years
Secondary	ORR Per RECIST 1.1 in PD-L1 Positive Participants	On-study imaging was to be performed every 9 weeks after the first dose of study drug, or more frequently if clinically indicated. ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). The percentage of PD-L1 positive participants who experienced a CR or PR is presented.	Up to 2 years
Secondary	PFS by RECIST 1.1 in PD-L1 Positive Participants	PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central radiologists' review or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm in the sum of lesions, OR the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and is reported in months. The median PFS for all PD-L1 positive participants is presented.	Up to 2 years
Secondary	DOR by RECIST 1.1 in PD-L1 Positive Participants	DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed using the Kaplan-Meier method and is reported in days. The median DOR for all PD-L1 positive participants with a confirmed response is presented.	Up to 2 years
Secondary	OS in PD-L1 Positive Participants	OS was defined as the time from the first day of study treatment to death due to any cause. OS is reported for all PD-L1 positive participants in months.	Up to 2 years
Secondary	ORR Per irRC in PD-L1 Positive Participants	ORR per irRC was defined as the percentage of participants in the analysis population who had a irCR (Complete disappearance of all tumor lesions [whether measureable or not, and no new lesions; irCR must be confirmed by repeated, consecutive assessments made no less than 4 weeks from the date first documented]) or irPR (Decrease in sum of the products of the two largest perpendicular diameters [SPD] of 50% or greater by a consecutive assessment at least 4 weeks after first documentation). The percentage of PD-L1 positive participants who experienced an irCR or irPR is presented.	Up to 2 years
Secondary	PFS Per irRC in PD-L1 Positive Participants	PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRC or death due to any cause, whichever occurred first. Using irRC, progressive disease was defined as at least a 25% increase in SPD relative to minimum recorded tumor burden. Confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented was required. Median PFS was analyzed using the Kaplan-Meier method and is presented in months for all PD-L1 positive participants.	Up to 2 years
Secondary	DOR Per irRC in PD-L1 Positive Participants	DOR was measured from the time measurement criteria were first met for irCR/irPR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). PD was defined as at least a 25% increase in SPD relative to minimum recorded tumor burden. Confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented was required. DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. DOR was analyzed using the Kaplan-Meier method, is reported in days and is presented for all PD-L1 positive participants who experienced an irCR or irPR.	Up to 2 years

External Links

•   Merck Oncology Clinical Trials Information