A Study of V940 Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Non-small Cell Lung Cancer (V940-002)

Non-small Cell Lung Cancer Clinical Trial

— INTerpath-002  

Official title:

A Phase 3, Randomized, Double-blind, Placebo- and Active-Comparator-Controlled Clinical Study of Adjuvant V940 (mRNA-4157) Plus Pembrolizumab Versus Adjuvant Placebo Plus Pembrolizumab in Participants With Resected Stage II, IIIA, IIIB (N2) Non-small Cell Lung Cancer (INTerpath-002)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06077760
• Other study ID #: V940-002
• Secondary ID: 2023-504923-20U1
• Status: Recruiting
• Phase: Phase 3
• Start date: December 6, 2023
• Est. completion date: December 21, 2035

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to evaluate V940 plus pembrolizumab versus placebo plus pembrolizumab for the adjuvant treatment of completely resected (R0) Stage II, IIIA, IIIB (with nodal involvement [N2]) non-small cell lung cancer (NSCLC). The primary hypothesis is that V940 plus pembrolizumab is superior to placebo plus pembrolizumab with respect to disease-free survival (DFS) as assessed by the investigator.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 868
• Est. completion date: December 21, 2035
• Est. primary completion date: June 25, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Has surgically resected and histologically confirmed diagnosis of pathological Stage II, IIIA, IIIB (N2) squamous or nonsquamous NSCLC as per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines.

• Has no evidence of disease before randomization.

• Has received at least one dose of adjuvant treatment with standard of care platinum doublet chemotherapy.

• No more than 24 weeks have elapsed between surgical resection of curative intent and the first dose of pembrolizumab.

• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.

• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.

• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART).

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• Diagnosis of small cell lung cancer (SCLC) or, for mixed tumors, presence of small cell elements, or has a neuroendocrine tumor with large cell components or a sarcomatoid carcinoma.

• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.

• Received prior neoadjuvant therapy for their current NSCLC diagnosis.

• Received or is a candidate to receive radiotherapy for their current NSCLC diagnosis.

• Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-PD-ligand 1 (L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.

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

• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.

• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.

• 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 to the first dose of study medication.

• Known additional malignancy that is progressing or has required active treatment within the past 5 years.

• Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.

• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

• Active infection requiring systemic therapy.

Related Conditions & MeSH terms

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

Intervention

Biological:
• V940
IM injection
• Pembrolizumab
IV infusion

Other:
• Placebo
IM injection

Locations

Country	Name	City	State
Argentina	Clinica Adventista Belgrano-Oncology ( Site 2901)	Caba
Argentina	Instituto de Investigaciones Clínicas Mar del Plata ( Site 2908)	Mar del Plata	Buenos Aires
Argentina	Fundacion Estudios Clinicos-Oncology ( Site 2907)	Rosario	Santa Fe
Australia	Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0203)	Melbourne	Victoria
Australia	St Vincent's Hospital-Oncology Clinical Trials ( Site 0202)	Melbourne	Victoria
Australia	One Clinical Research ( Site 0200)	Nedlands	Western Australia
Canada	Centre Hospitalier de l'Université de Montréal ( Site 0104)	Montréal	Quebec
Canada	McGill University Health Centre ( Site 0100)	Montréal	Quebec
Chile	Bradfordhill-Clinical Area ( Site 3103)	Santiago	Region M. De Santiago
Chile	FALP-UIDO ( Site 3100)	Santiago	Region M. De Santiago
Chile	Orlandi Oncologia-Oncology ( Site 3102)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile-Centro del Cáncer ( Site 3104)	Santiago	Region M. De Santiago
Chile	ONCOCENTRO APYS ( Site 3105)	Viña del Mar	Valparaiso
Costa Rica	CIMCA ( Site 3300)	San José	San Jose
Costa Rica	ICIMED ( Site 3301)	San José	San Jose
Czechia	Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 0700)	Brno	Brno-mesto
Czechia	Fakultni nemocnice Olomouc-Klinika plicnich nemoci a tuberkulozy ( Site 0701)	Olomouc
Czechia	Nemocnice AGEL Ostrava - Vitkovice a.s.-Plicni odd ( Site 0702)	Ostrava	Ostrava Mesto
Estonia	North Estonia Medical Centre Foundation-Chemotherapy ( Site 0901)	Tallinn	Harjumaa
France	Institut de Cancérologie de l'Ouest ( Site 1101)	ANGERS cedex 02	Maine-et-Loire
France	CHU GABRIEL MONTPIED ( Site 1105)	Clermont-Ferrand	Puy-de-Dome
France	Hôpital Arnaud de Villeneuve - CHU Montpellier ( Site 1102)	Montpellier	Herault
France	CHU Bordeaux Haut-Leveque ( Site 1106)	Pessac	Aquitaine
France	Nouvel Hôpital Civil (NHC)-Service de pneumologie ( Site 1100)	Strasbourg	Alsace
Greece	European Interbalkan Medical Center-Oncology Department ( Site 1302)	Thessaloniki
Hungary	Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz - Pulmonologia Osztaly ( Site 1404)	Gyor	Gyor-Moson-Sopron
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 1407)	Kaposvár	Somogy
Hungary	Bacs-Kiskun Varmegyei Oktatokorhaz-Onkoradiologiai Kozpont ( Site 1401)	Kecskemét	Bacs-Kiskun
Hungary	Pécsi Tudományegyetem Klinikai Központ-Onkoterápiás Intézet ( Site 1402)	Pécs	Baranya
Italy	Azienda Ospedaliero Universitaria Maggiore della Carità ( Site 1502)	Novara
Italy	AO Santa Maria della Misericordia-Oncology Department ( Site 1501)	Perugia	Umbria
Italy	P.O. "S. Maria della Misericordia" Azienda Sanitaria Univers-Oncology Department ( Site 1506)	Udine	Friuli-Venezia Giulia
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno klinikos-Pulmonology ( Site 1701)	Kaunas	Kauno Apskritis
Lithuania	National Cancer Institute-Department of Thoracic Surgery and Oncology ( Site 1700)	Vilnius	Vilniaus Miestas
New Zealand	Harbour Cancer & Wellness ( Site 0301)	Auckland
New Zealand	New Zealand Clinical Research (Christchurch) ( Site 0300)	Christchurch	Canterbury
Norway	Drammen Sykehus, Vestre Viken HF ( Site 1903)	Drammen	Buskerud
Norway	Akershus Universitetssykehus-Avdeling for lungesykdommer ( Site 1900)	Lørenskog	Akershus
Norway	Stavanger Universitetssykehus ( Site 1901)	Stavanger	Rogaland
Poland	Bialostockie Centrum Onkologii ( Site 2005)	Bialystok	Podlaskie
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2003)	Bydgoszcz	Kujawsko-pomorskie
Poland	Wielkopolskie Centrum Pulmonologii i Torakochirurgii-Oddzial Onkologii Klinicznej z Pododdzialem Dz	Poznan	Wielkopolskie
Poland	Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 2001)	Przemysl	Podkarpackie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier	Warszawa	Mazowieckie
Portugal	Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 2702)	Porto
Spain	Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 2400)	Barcelona
Spain	Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 2401)	Hospitalet	Barcelona
Spain	HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA-Medical Oncology ( Site 2403)	Majadahonda	Madrid, Comunidad De
Spain	Hospital Quirón Málaga ( Site 2405)	Málaga	Malaga
Spain	HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 2402)	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Virgen Macarena-Unidad de Investigación Oncológica ( Site 2404)	Sevilla
Taiwan	Changhua Christian Hospital ( Site 0504)	Changhua County	Changhua
Taiwan	National Taiwan University Hospital - Hsinchu branch ( Site 0501)	Hsinchu
Taiwan	Taichung Veterans General Hospital-Chest ( Site 0503)	Taichung
Taiwan	National Cheng Kung University Hospital-Clinical Trial Center ( Site 0505)	Tainan
Taiwan	National Taiwan University Hospital-Oncology ( Site 0506)	Taipei
Taiwan	Taipei Medical University Hospital ( Site 0502)	Taipei
Taiwan	National Taiwan University Cancer Center (NTUCC) ( Site 0500)	Taipei City	Taipei
United States	St. Vincent Frontier Cancer Center ( Site 0043)	Billings	Montana
United States	Montefiore Medical Center- Montefiore Medical Park-Oncology ( Site 0080)	Bronx	New York
United States	Medical University of South Carolina-Hollings Cancer Center ( Site 0050)	Charleston	South Carolina
United States	University Hospitals Cleveland Medical Center ( Site 0023)	Cleveland	Ohio
United States	UCHealth Memorial Hospital-Heme Onc ( Site 0052)	Colorado Springs	Colorado
United States	Good Samaritan Regional Medical Center-Samaritan Pastega Regional Cancer Center ( Site 0082)	Corvallis	Oregon
United States	Altru Health System ( Site 0040)	Grand Forks	North Dakota
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 0036)	Hackensack	New Jersey
United States	The University of Louisville, James Graham Brown Cancer Center ( Site 0037)	Louisville	Kentucky
United States	Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0012)	Marietta	Georgia
United States	Perlmutter Cancer Center at NYU Langone Hospital - Long Island-Clinical Research Department ( Site 0	Mineola	New York
United States	Laura and Isaac Perlmutter Cancer Center ( Site 0010)	New York	New York
United States	Memorial Sloan Kettering Cancer Center ( Site 0029)	New York	New York
United States	Mid Florida Hematology and Oncology Center ( Site 0014)	Orange City	Florida
United States	Beacon Cancer Care ( Site 0044)	Post Falls	Idaho
United States	Sanford Cancer Center ( Site 0075)	Sioux Falls	South Dakota

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	ModernaTX, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  Costa Rica,  Czechia,  Estonia,  France,  Greece,  Hungary,  Italy,  Lithuania,  New Zealand,  Norway,  Poland,  Portugal,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease- Free Survival (DFS)	DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, as assessed by the investigator, or death due to any cause, whichever occurs first.	Up to ~78 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~12 years
Secondary	Distant Metastasis-Free Survival (DMFS)	DMFS is defined as the time from randomization to the first diagnosis of a distant metastasis as assessed by the investigator, or death due to any cause, whichever occurs first.	Up to ~12 years
Secondary	Lung Cancer Specific Survival (LCSS)	LCSS is defined as the time from randomization to death due to lung cancer.	Up to ~12 years
Secondary	Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" will be scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a better overall health status. The change from baseline in global health status/quality of life (EORTC QLQ-C30 Items 29 and 30) combined score will be presented.	Baseline and up to ~12 years
Secondary	Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a worse level of physical functioning. The change from baseline in physical functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.	Baseline and up to ~12 years
Secondary	Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and " Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a worse level of role functioning. The change from baseline in role functioning (EORTC QLQ-C30 Items 6 and 7) combined score will be presented.	Baseline and up to ~12 years
Secondary	Change from Baseline in the EORTC QLQ-C30 Dyspnea (Item 8) Score on the EORTC QLQ-C30	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a worse level of dyspnea. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented.	Baseline and up to ~12 years
Secondary	Change from Baseline in the EORTC QLQ-Lung Cancer Questionnaire (LC24) Coughing (Items 31 and 52) Combined Score on the EORTC QLQ-LC24	The EORTC QLQ-LC24 is a lung cancer specific health-related quality of life questionnaire. Participant responses to questions about coughing will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. A higher score indicates more coughing. The change from baseline in coughing (EORTC QLQ-LC24 Items 31 and 52) combined score will be presented.	Baseline and up to ~12 years
Secondary	Change from Baseline in the EORTC QLQ-LC24 Chest Pain (Item 40) Score on the EORTC QLQ-LC24	The EORTC QLQ-LC24 is a lung cancer specific health-related quality of life questionnaire. Participant responses to the question "Have you had pain in your chest?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. A higher score indicates more chest pain. The change from baseline in chest pain (EORTC QLQ-LC24 Item 40) score will be presented.	Baseline and up to ~12 years
Secondary	Number of Participants Who Experience 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.	Up to ~15 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an 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.	Up to ~12 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary