A Study of Subcutaneous (SC) Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) vs Intravenous Pembrolizumab in Adult Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) (MK-3475A-D77)-Japan Extension

Metastatic Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase 3 Randomized, Open-label Clinical Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Versus Intravenous Pembrolizumab, Administered With Chemotherapy, in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06212752
• Other study ID #: 3475A-D77 Japan Extension
• Secondary ID: MK-3475A-D772022
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 13, 2023
• Est. completion date: May 22, 2028

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to assess the pharmacokinetics (PK) and safety of SC MK-3475A vs intravenous (IV) pembrolizumab, administered with chemotherapy in first line treatment of adult Japanese participants with metastatic non-small cell lung cancer. The primary hypotheses of this study are MK-3475A subcutaneous (SC) is noninferior to pembrolizumab IV with respect to PK parameters.

Description:

Japan extension study will require approximately six years which includes one additional year (beyond the global study's last participant last study related contact) from the time the first participant (or their legally acceptable representative) provides informed consent until the last participant's last study related contact to complete.

The Japan extension study will include participants previously enrolled in Japan in the global study for MK-3475A-D77 (NCT05722015) plus the study will continue to enroll participants in Japan until the sample size for participants in Japan reaches approximately 39.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 378
• Est. completion date: May 22, 2028
• Est. primary completion date: September 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has histologically or cytologically confirmed diagnosis of squamous or non-squamous Non-small Cell Lung Cancer (NSCLC).

• Must provide archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated.

• Has a life expectancy of at least 3 months.

Exclusion Criteria:

• Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.

• Has received prior systemic anticancer therapy for metastatic NSCLC.

• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.

• Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicity requiring corticosteroids.

• Has received radiation therapy to the lung (>30 Gray) within 6 months of start of study intervention.

• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

• Has an active autoimmune disease that has required systemic treatment in past 2 years.

• Has an active infection requiring systemic therapy.

• Has a history of human immunodeficiency virus (HIV) infection.

• Has a history of Hepatitis B or C.

• Has not adequately recovered from major surgery or has ongoing surgical complications.

• Has a history of allogenic tissue/solid organ transplant.

Related Conditions & MeSH terms

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

Intervention

Biological:
• Pembrolizumab coformulated with hyaluronidase
MK3475A SC will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.

Drug:
• Pemetrexed
Pemetrexed 500 mg/m² by IV Infusion will be administered for nonsquamous NSCLC as per the schedule specified in arm.
• Cisplatin
Cisplatin 75 mg/m² by IV Infusion will be administered for nonsquamous and squamous NSCLC as per the schedule specified in arm.
• Carboplatin
Carboplatin AUC 5 mg/mL/min in nonsquamous and AUC 6 mg/mL/min in squamous NSCLC will be administered as per the schedule specified in arm.
• Paclitaxel
Paclitaxel 200 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.
• Nab-paclitaxel
Nab-paclitaxel 100 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.

Biological:
• Pembrolizumab
Pembrolizumab by IV Infusion will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.

Drug:
• Filgrastim
Filgrastim will be administered as per the schedule specified for the arm.
• Pegylated filgrastim
Pegylated filgrastim will be administered as per the schedule specified for the arm.

Locations

Country	Name	City	State
Japan	Juntendo University Hospital ( Site 4413)	Bunkyo-ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center ( Site 4410)	Fukuoka
Japan	National Hospital Organization Kyushu Medical Center ( Site 4411)	Fukuoka
Japan	Kansai Medical University Hospital ( Site 4408)	Hirakata	Osaka
Japan	Saitama Prefectural Cancer Center ( Site 4402)	Ina-machi	Saitama
Japan	Kurashiki Central Hospital ( Site 4409)	Kurashiki	Okayama
Japan	Kurume University Hospital ( Site 4412)	Kurume	Fukuoka
Japan	Shizuoka Cancer Center ( Site 4405)	Nagaizumi-cho,Sunto-gun	Shizuoka
Japan	Miyagi Cancer Center ( Site 4401)	Natori	Miyagi
Japan	Osaka International Cancer Institute ( Site 4407)	Osaka
Japan	Gunma Prefectural Cancer Center ( Site 4416)	Otashi	Gunma
Japan	National Hospital Organization Hokkaido Cancer Center ( Site 4415)	Sapporo	Hokkaido
Japan	Sendai Kousei Hospital ( Site 4400)	Sendai	Miyagi
Japan	Osaka Medical and Pharmaceutical University Hospital ( Site 4414)	Takatsuki	Osaka
Japan	Nippon Medical School Hospital ( Site 4403)	Tokyo
Japan	Fujita Health University ( Site 4406)	Toyoake	Aichi
Japan	Tochigi Cancer Center ( Site 4417)	Utsunomiya	Tochigi
Japan	Kanagawa Cardiovascular and Respiratory Center ( Site 4404)	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	ORR was defined as the percentage of participants who have a confirmed 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) per RECIST 1.1 as assessed by BICR.	Up to ~72 months
Secondary	Area Under the Curve (AUC) of Pembrolizumab Measured After the First Dose	AUC is defined as area under curve exposure. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC.	At designated time points (Up to ~14 months)
Secondary	Trough Concentration (Ctrough) of Pembrolizumab Measured at Steady State	Ctrough is defined as the trough concentration at steady-state. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough.	At designated time points (Up to ~18 months)
Secondary	Maximum Serum Concentration (Cmax) of Pembrolizumab Measured After the First Dose	Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax.	At designated time points (Up to ~28 months)
Secondary	Trough Concentration (Ctrough) of Pembrolizumab Measured After the First Dose	Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough.	At designated time points (Up to ~28 months)
Secondary	Area Under the Curve (AUC) of Pembrolizumab Measured at Steady State	AUC is defined as area under curve exposure at steady state. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC.	At designated time points (Up to ~28 months)
Secondary	Maximum Serum Concentration (Cmax) of Pembrolizumab Measured at Steady State	Cmax is defined as the peak concentration over the dosing interval in steady-state. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax	At designated time points (Up to ~28 months)
Secondary	Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab	Blood samples are to be collected at designated time points for the determination of the presence or absence of anti-pembrolizumab antibodies. The percentage of participants who develop anti pembrolizumab antibodies will be reported.	At designated time points (Up to ~28 months)
Secondary	Progression-free Survival (PFS) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first.	Up to ~72 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~72 months
Secondary	Duration of Response (DOR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)	For participants who show confirmed CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.	Up to ~72 months
Secondary	Number of Participants Who Experienced at Least One Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with an AE will be reported for Arms 1 and 2.	Up to~28 months
Secondary	Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported for Arms 1 and 2.	Up to~25 months
Secondary	Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Score-Items 29 and 30	EORTC QLQ-C30 is a psychometrically and clinically validated instrument appropriate for assessing HRQoL in oncology studies. The EORTC QLQ-C30 is the most widely used cancer-specific HRQoL instrument, which contains 30 items and measures 5 functional dimensions (physical, role, emotional, cognitive and social), 3 symptom items (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. For the global health status or QoL and function scales, a higher value indicates a better level of function; for symptom scales and items, a higher value indicates increased severity of symptoms.	Baseline and up to ~28 months
Secondary	Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Physical Functioning Score-Items 1 to 5	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome and will provide data to develop health utilities for use in health economic analyses. The 5 health state dimensions in the EQ-5D-5L include the following: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension is rated on a 5-point scale from 1 (no problem) to 5 (unable to/extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates his or her general state of health at the time of the assessment. This instrument has been used extensively in cancer studies and published results from these studies support its validity and reliability.	Baseline and up to ~28 months
Secondary	Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Role Functioning Score-Items 6 and 7	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome and will provide data to develop health utilities for use in health economic analyses. The 5 health state dimensions in the EQ-5D-5L include the following: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension is rated on a 5-point scale from 1 (no problem) to 5 (unable to/extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates his or her general state of health at the time of the assessment. This instrument has been used extensively in cancer studies and published results from these studies support its validity and reliability.	Baseline and up to ~28 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary