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)

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: NCT05722015
• Other study ID #: 3475A-D77
• Secondary ID: 2022-501506-36-0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 14, 2023
• Est. completion date: May 22, 2028

Study information

• Verified date: February 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 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.

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
Argentina	Hospital Italiano de Buenos Aires-Clinical Oncology ( Site 1005)	ABB	Caba
Argentina	Instituto Argentino de Diagnóstico y Tratamiento (IADT) ( Site 1002)	Buenos Aires
Argentina	Clinica Adventista Belgrano-Oncology ( Site 1004)	Caba
Argentina	Instituto Alexander Fleming ( Site 1008)	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Hospital Italiano de Córdoba ( Site 1000)	Cordoba
Argentina	Instituto de Investigaciones Clínicas Mar del Plata ( Site 1001)	Mar del Plata	Buenos Aires
Argentina	Sanatorio Parque ( Site 1003)	Rosario	Santa Fe
Brazil	CRIO - CENTRO REGIONAL INTEGRADO DE ONCOLOGIA-Pesquisa Clínica ( Site 1102)	Fortaleza	Ceara
Brazil	Instituto Joinvilense de Hematologia e Oncologia ( Site 1101)	Joinville	Santa Catarina
Brazil	Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 1100)	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Câncer de Recife ( Site 1107)	Recife	Pernambuco
Brazil	A. C. Camargo Cancer Center ( Site 1106)	Sao Paulo
Chile	IC La Serena Research ( Site 1207)	La Serena	Coquimbo
Chile	Bradfordhill-Clinical Area ( Site 1202)	Santiago	Region M. De Santiago
Chile	FALP-UIDO ( Site 1203)	Santiago	Region M. De Santiago
Chile	Instituto Nacional del Cancer-CR Investigación ( Site 1211)	Santiago	Region M. De Santiago
Chile	Oncovida ( Site 1209)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 1210)	Santiago	Region M. De Santiago
Chile	Oncocentro Valdivia ( Site 1201)	Valdivia	Los Rios
China	Beijing Cancer hospital-intrathoratic deparmtment II ( Site 4510)	Beijing	Beijing
China	Beijing Chest Hospital,Capital Medical University ( Site 4511)	Beijing	Beijing
China	Beijing Peking Union Medical College Hospital-pneumology department ( Site 4501)	Beijing	Beijing
China	Fujian Provincial Cancer Hospital ( Site 4517)	Fuzhou	Fujian
China	Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine (	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University-Respiratory Department ( Site 4514)	Hangzhou	Zhejiang
China	Anhui Provincial Hospital-Cancer Chemotherapy Department ( Site 4503)	Hefei	Anhui
China	Jiangmen Center Hospital ( Site 4509)	Jiangmen	Guangdong
China	The First Affiliated Hospital of Nanchang University-Respiratory Medicine Department ( Site 4515)	Nanchang	Jiangxi
China	Fudan University Shanghai Cancer Center-Oncology ( Site 4512)	Shanghai	Shanghai
China	ShenZhen People's Hospital ( Site 4504)	Shenzhen	Guangdong
China	Shanxi Cancer Hospital ( Site 4521)	Taiyuan	Shanxi
China	Taizhou Hospital of Zhejiang Province-Respiratory ( Site 4508)	Taizhou	Zhejiang
China	Tianjin Chest Hospital ( Site 4518)	Tianjin	Tianjin
China	Chongqing Three Gorges Central Hospital ( Site 4516)	Wanzhou	Chongqing
China	Wuhan Union Hospital Cancer Center-Cancer center ( Site 4502)	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University ( Site 4520)	Xi'an	Shaanxi
France	Hopitaux Universitaires Paris Centre-Hopital Cochin ( Site 2603)	Paris
France	Centre Hospitalier de Cornouaille Quimper - Concarneau ( Site 2600)	Quimper	Finistere
France	Centre Hospitalier Régional Universitaire de Tours - Hôpital Bretonneau ( Site 2602)	Tours	Indre-et-Loire
Guatemala	Private Practice- Dr. Rixci Augusto Lenin Ramírez ( Site 1404)	Ciudad de Guatemala
Guatemala	MEDI-K CAYALA ( Site 1403)	Guatemala
Guatemala	Centro Medico Integral De Cancerología (CEMIC) ( Site 1400)	Quetzaltenango
Guatemala	Centro Regional de Sub Especialidades Médicas SA ( Site 1401)	Quetzaltenango
Hungary	Országos Korányi Pulmonológiai Intézet-VI. Tüdöbelosztály és Bronchológia ( Site 2100)	Budapest
Hungary	Semmelweis Egyetem-Pulmonológiai Klinika ( Site 2104)	Budapest
Hungary	Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2102)	Kecskemét	Bacs-Kiskun
Hungary	Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 2103)	Szolnok	Jasz-Nagykun-Szolnok
Hungary	Törökbálinti Tüdogyógyintézet ( Site 2105)	Törökbálint	Pest
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
Poland	Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 2801)	Koszalin	Zachodniopomorskie
Poland	Warminsko - Mazurskie Centrum Chorób Pluc w Olsztynie-Oddzial Onkologii z Pododdzialem Chemioterapii	Olsztyn	Warminsko-mazurskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier	Warszawa	Mazowieckie
Romania	Institutul Oncologic-Oncologie Medicala ( Site 2302)	Cluj
Romania	Centrul de Oncologie "Sfântul Nectarie"-Medical Oncology ( Site 2301)	Craiova	Dolj
Romania	SC Radiotherapy Center Cluj SRL-Oncologie Medicala ( Site 2303)	Flore?ti	Cluj
Romania	Cabinet Medical Oncomed ( Site 2305)	Timi?oara	Timis
South Africa	Cape Town Oncology Trials ( Site 2902)	Cape Town	Western Cape
South Africa	The Oncology Centre ( Site 2901)	Durban	Kwazulu-Natal
South Africa	Medical Oncology Centre of Rosebank ( Site 2907)	Johannesburg	Gauteng
South Africa	CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 2903)	Port Elizabeth	Eastern Cape
South Africa	Steve Biko Academic Hospital-Medical Oncology ( Site 2904)	Pretoria	Gauteng
South Africa	Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 2900)	Sandton	Gauteng
Spain	Hospital Universitari Vall d'Hebron-Oncology ( Site 2400)	Barcelona
Spain	Hospital Universitario Juan Ramon Jimenez-Oncología Medica ( Site 2402)	Huelva
Spain	HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 2401)	Madrid	Madrid, Comunidad De
Spain	CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 2404)	Santiago de Compostela	La Coruna
Taiwan	Changhua Christian Hospital ( Site 4203)	Changhua County	Changhua
Taiwan	E-Da hospital ( Site 4208)	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 4207)	Kaohsiung
Taiwan	Chang Gung Memorial Hospital at Kaohsiung ( Site 4200)	Kaohsiung Niao Sung Dist	Kaohsiung
Taiwan	National Cheng Kung University Hospital ( Site 4202)	Tainan
Taiwan	National Taiwan University Hospital-Oncology ( Site 4204)	Taipei
Taiwan	National Taiwan University Cancer Center (NTUCC) ( Site 4205)	Taipei City	Taipei
Thailand	Chulalongkorn University ( Site 4301)	Bangkok	Krung Thep Maha Nakhon
Thailand	Songklanagarind hospital ( Site 4302)	Hatyai	Songkhla
Thailand	Maharaj Nakorn Chiang Mai Hospital ( Site 4300)	Muang	Chiang Mai
Thailand	Division of Medical Oncology, Siriraj H ( Site 4303)	Siriraj	Krung Thep Maha Nakhon
Turkey	Ankara City Hospital-Medical Oncology ( Site 2501)	Ankara
Turkey	Gulhane Egitim Arastirma Hastanesi-Oncology ( Site 2504)	Ankara
Turkey	Hacettepe Universite Hastaneleri-oncology hospital ( Site 2506)	Ankara
Turkey	TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 2502)	Istanbul
Turkey	I.E.U. Medical Point Hastanesi-Oncology ( Site 2507)	Izmir, Karsiyaka	Izmir
Turkey	Memorial Kayseri Hastanesi ( Site 2500)	Kayseri
Turkey	Inönü Üniversitesi Turgut Özal Tip Merkezi-medical oncology depertmant ( Site 2503)	Malatya
United States	Central Care Cancer Center - Bolivar ( Site 0017)	Bolivar	Missouri
United States	University of Illinois at Chicago-University of Illinois Cancer Center ( Site 0022)	Chicago	Illinois
United States	Clermont Oncology Center ( Site 0018)	Clermont	Florida
United States	Hattiesburg Clinic Hematology/Oncology ( Site 0008)	Hattiesburg	Mississippi
United States	Franciscan Health Lafayette East ( Site 0020)	Lafayette	Indiana
United States	Mid Florida Hematology and Oncology Center ( Site 0010)	Orange City	Florida
United States	Mercy Health-Paducah Medical Oncology and Hematology ( Site 0006)	Paducah	Kentucky
United States	St. Joseph's Hospital and Medical Center-Dignity Health Cancer Institute ( Site 0023)	Phoenix	Arizona
United States	Orchard Healthcare Research Inc. ( Site 0011)	Skokie	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Chile,  China,  France,  Guatemala,  Hungary,  Japan,  Poland,  Romania,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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	Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)	The ORR is defined as the percentage of participants who achieve a confirmed CR or PR per RECIST 1.1 as assessed by BICR.	Up to~60 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~60 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to~60 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~60 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