Study of Eftilagimod Alfa (Efti) in Combination With Pembrolizumab and Chemotherapy Versus Placebo in Combination With Pembrolizumab and Chemotherapy in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC) (TACTI-004)
TACTI-004, a Double-Blinded, Randomized Phase 3 Trial in Patients With Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC) Receiving Eftilagimod Alfa (MHC Class II Agonist) in Combination With Pembrolizumab (PD-1 Antagonist) and Chemotherapy.
5 other identifiers
interventional
756
26 countries
145
Brief Summary
The purpose of this study is to compare eftilagimod alfa (efti) in combination with pembrolizumab and chemotherapy versus placebo in combination with pembrolizumab and chemotherapy with respect to overall survival (OS) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) among adults with metastatic non-small cell lung cancer (NSCLC). Participants will receive either efti plus standard treatment (pembrolizumab and platinum doublet chemotherapy) or placebo plus standard treatment and will be treated for up to 2 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2025
Typical duration for phase_3
145 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 3, 2024
CompletedFirst Posted
Study publicly available on registry
December 10, 2024
CompletedStudy Start
First participant enrolled
March 21, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2029
March 18, 2026
November 1, 2025
2.2 years
December 3, 2024
March 17, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Determination of Overall survival (OS)
Up to approximately 54 months
Determination of Progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Up to approximately 54 months
Secondary Outcomes (6)
Determination of Objective response rate (ORR) per RECIST 1.1
Up to approximately 54 months
Frequency of adverse events (AEs)
Up to approximately 27 months
Severity of adverse events (AEs) according to the United States National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v5.0
Up to approximately 27 months
Determination of Time to Response (TTR) by RECIST 1.1.
Up to approximately 54 months
Determination of Duration of Response (DOR) by RECIST 1.1.
Up to approximately 54 months
- +1 more secondary outcomes
Study Arms (2)
efti + Standard of Care arm
EXPERIMENTALCombination of efti, pembrolizumab (KEYTRUDA®) and histology-based platinum doublet chemotherapy
Placebo + Standard of Care arm
PLACEBO COMPARATORCombination of efti-matching placebo, pembrolizumab (KEYTRUDA®) and histology-based platinum doublet chemotherapy
Interventions
30 mg of efti every 2 weeks subcutaneously for the first 6 months, thereafter every 3 weeks for up to 24 months in total
For participants with squamous histology for 4 cycles (1 cycle = 3 weeks) as follows: every 3 weeks: carboplatin area under the curve (AUC) 5 or 6 in combination with paclitaxel 175 mg/m2 or 200 mg/m2
For participants with nonsquamous histology for 4 cycles (1 cycle = 3 weeks) as follows: every 3 weeks: cisplatin 75 mg/m2 or carboplatin AUC 5 or 6 in combination with pemetrexed 500 mg/m2. After the initial 4 cycles, pemetrexed 500 mg/m2 maintenance therapy will be administered every 3 weeks
200 mg pembrolizumab (KEYTRUDA®) every 3 weeks i.v. for up to approximately 24 months
efti-matching placebo every 2 weeks subcutaneously for the first 6 months, thereafter every 3 weeks for up to 24 months in total
Eligibility Criteria
You may qualify if:
- Participants may be enrolled if they meet all of the following criteria at screening:
- Willing to give written informed consent and to comply with the protocol.
- Histologically- or cytologically-confirmed diagnosis of advanced or metastatic (stage IIIB/C or stage IV) non-small cell lung cancer (NSCLC) not amenable to curative treatment or locally available oncogenic driver mutation-based first-line therapy, treatment naïve for systemic therapy given for advanced/metastatic disease.
- Archival tumor tissue sample or newly obtained core, or excisional biopsy of a tumor lesion not previously irradiated has been provided. Details pertaining to tumor tissue submission can be found in the Laboratory Manual.
- Availability of programmed death-ligand 1 (PD-L1) biomarker result from central laboratory, using the Food and Drug Administration (FDA) approved Dako standardized diagnostic test (PD-L1 IHC 22C3 pharmDx).
- Be ≥ 18 years of age on the day of signing the informed consent.
- Participants assigned male at birth must follow specific contraception guidelines during and after the trial intervention period. The required contraception duration varies by drug. Participants must refrain from donating sperm and either remain abstinent or use condoms with an additional contraceptive method during intercourse with a nonpregnant partner. Contraceptive measures must adhere to local regulations, with stricter local label requirements taking precedence over the trial's guidelines.
- A participant of childbearing potential (POCBP) is eligible if they are not pregnant, confirmed by a negative pregnancy test before the first trial dose. They must not breastfeed during the trial or for a defined duration after the last dose of each drug. POCBPs must use highly effective contraception, with low user dependency or long-term abstinence during and after the trial intervention, and refrain from egg donation or storage. The required contraception duration varies by drug. Local contraception regulations must be followed.
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization.
- Expected survival \> 3 months.
- Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by site.
- Participants must have recovered from all AEs due to previous anticancer therapies to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 ≤ Grade 1 or baseline. Participants with CTCAE ≤ Grade 2 neuropathy, alopecia, and elevated transaminases in case of liver metastases may be eligible.
- Participants who received major surgery prior to trial start must have recovered adequately from the toxicity and/or complications from the intervention prior to starting trial treatment.
- 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 and have completed curative antiviral therapy at least 4 weeks prior to randomization.
- +2 more criteria
You may not qualify if:
- Participants are to be excluded from the trial at the time of screening for any of the following reasons:
- Is expected to require any other form of systemic or localized antineoplastic therapy (other than the trial treatment) while on trial (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection).
- Received prior radiotherapy within 2 weeks of start of trial intervention, or has radiation-related toxicities, requiring corticosteroids.
- Participants whose tumor harbors any of the following actionable molecular alterations:
- Epidermal growth factor receptor (EGFR)-sensitizing (activating) mutation
- Anaplastic lymphoma kinase (ALK) gene fusion positive (ALK translocation)
- c-ROS oncogene 1 (ROS1) translocation
- For any indication has received any of the following therapies
- within 3 weeks prior to cycle 1 day 1: systemic cytotoxic chemotherapy, targeted small molecule therapy (e.g. kinase inhibitors), biological therapy, any other systemic cancer therapy or had major surgery;
- within 4 weeks prior to cycle 1 day 1 has been treated with an investigational agent or has used an investigational device, or is still a participant in the active phase of an investigational trial;
- within 6 months prior to cycle1 day 1 received lung radiation therapy of \>30 Gray (Gy).
- Has received any treatment as part of adjuvant, neoadjuvant therapy or definitive chemoradiation for the treatment of NSCLC within 12 months prior to the diagnosis of advanced/metastatic disease.
- Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX40, CD137) or Lymphocyte Activation Gene 3 (LAG-3) targeting therapy (e.g., anti-LAG-3 antibodies). Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent for nonmetastatic resectable NSCLC (e.g. in the neoadjuvant or adjuvant setting) or following definitive chemoradiation, is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.
- Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during trial screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of trial intervention.
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Immutep S.A.S.lead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (147)
Norton Cancer Institute - Audubon
Louisville, Kentucky, 40217, United States
New Mexico Oncology Hematology Consultants, Ltd.
Albuquerque, New Mexico, 87109, United States
Ascension Seton Infusion Center
Austin, Texas, 78712, United States
Centro de Endocrinologia y Diabetes Dr. Raul A. Gutman SRL
Buenos Aires, Argentina
Fundacion Respirar
Buenos Aires, Argentina
Hospital Británico de Buenos Aires
Buenos Aires, Argentina
Sanatorio Parque - Rosario
Rosario, Argentina
Clinica Viedma
Viedma, Argentina
Lyell McEwin Hospital
Elizabeth Vale, Australia
Greenslopes Private Hospital
Greenslopes, Australia
The Alfred Hospital
Melbourne, Australia
Tasman Oncology Research Ltd
Southport, Australia
St John of God Subiaco Hospital
Subiaco, Australia
Royal Darwin Hospital
Tiwi, Australia
Calvary Mater Newcastle
Waratah, Australia
Cancer Care Wollongong Pty Limited
Wollongong, Australia
Landeskrankenhaus-Universitätsklinikum Graz, KLinische Abteilung für Pulmonologie
Graz, Austria
Vienna General Hospital
Vienna, Austria
Antwerp University Hospital
Antwerp, Belgium
Algemeen Ziekenhuis Maria Middelares
Ghent, Belgium
Clinique et Maternité Sainte-Elisabeth
Namur, Belgium
Universidade de Caxias do Sul
Caxias do Sul, Brazil
Centro Integrado de Oncologia de Curitiba - CIONC
Curitiba, Brazil
Cetus Oncologia Hospital Dia - Belo Horizonte
Horizonte, Brazil
Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
Ijuí, Brazil
Hospital Nossa Senhora da Conceicao (HNSC)
Porto Alegre, Brazil
Santa Casa de Misericórdia de Porto Alegre
Porto Alegre, Brazil
Hospital Beneficencia Portuguesa - Mirante
São Paulo, Brazil
Hospital Santa Rita - Vitoria
Vitória, Brazil
Multiprofile Hospital for Active Treatment - Dobrich AD
Dobrich, Bulgaria
Multiprofile Hospital For Active Treatment "Dr. Tota Venkova" AD
Gabrovo, Bulgaria
MHAT Uni Hospital OOD
Panagyurishte, Bulgaria
Complex Oncology Center Ruse
Rousse, Bulgaria
Multiprofile Hospital for Active Treatment Serdika EOOD
Sofia, Bulgaria
Brampton Civic Hospital
Brampton, Canada
McGill University - Jewish General Hospital (JGH) - Lady Davis Institute for Medical Research
Montreal, Canada
Unite de recherche clinique du CISSS des Laurentides
Saint-Jérôme, Canada
Centro de Oncologia de Precision
Las Condes, Chile
Facultad Odontología Unipac
Santiago, Chile
Klinički Bolnički Centar Osijek
Osijek, Croatia
Klinicka Bolnica Centar - Sestre Milosrdnice - Klinika Za Tumore (University Hospital for Tumors)
Zagreb, Croatia
Klinički Bolnički Centar Sestre Milosrdnice
Zagreb, Croatia
Klinički Bolnički Centar Zagreb - Klinika Za Plućne Bolesti Jordanovac
Zagreb, Croatia
High-tech Hospital Med Center
Batumi, Georgia
High Technology Medical Center, University Clinic
Tbilisi, Georgia
Institute of Clinical Oncology
Tbilisi, Georgia
Mardaleishvili Medical Centre
Tbilisi, Georgia
Klinikum St. Marien
Amberg, Germany
Klinikum Augsburg
Augsburg, Germany
HELIOS Klinikum Bad Saarow
Bad Saarow, Germany
Evangelische Lungenklinik Berlin
Berlin, Germany
Universitätsklinikum Köln
Cologne, Germany
Agaplesion Medizinisches Versorgungszentrum - Frankfurt gGmbH
Frankfurt, Germany
Universitätsklinikum Frankfurt
Frankfurt, Germany
Krankenhaus Nordwest
Frankfurt am Main, Germany
Asklepios Fachkliniken München-Gauting
Gauting, Germany
Krankenhaus Martha-Maria Halle-Dölau
Halle, Germany
Facharztzentrum Eppendorf
Hamburg, Germany
Gemeinschaftspraxis für Hämatologie und Onkologie
Münster, Germany
Robert-Bosch-Krankenhaus
Stuttgart, Germany
General Hospital of Athens "Laiko"
Athens, Greece
Sotiria Chest Diseases Hospital
Athens, Greece
University of Thessaly- General University Hospital of Larissa
Larissa, Greece
University of Patras - Rio Regional University Hospital
Pátrai, Greece
Metropolitan Hospital, Department of Oncology
Piraeus, Greece
Bioclinic of Thessaloniki
Thessaloniki, Greece
Interbalkan Medical Center of Thessaloniki
Thessaloniki, Greece
St. Luke's Hospital S.A.
Thessaloniki, Greece
Debreceni Egyetem Klinikai Központ
Debrecen, Hungary
Tolna Vármegyei Balassa János Kórház
Szekszárd, Hungary
HCG Cancer Centre - Double Road (Bangalore Institute of Oncology (BIO))
Bangalore, India
All India Institute of Medical Sciences (AIIMS) - Bhubaneswar
Bhubaneswar, India
Geri Care Hospital T.Nagar
Chennai, India
Voluntary Health Services Hospital
Chennai, India
Chittaranjan National Cancer Institute
Kolkata, India
Maulana Azad Medical College
New Delhi, India
Sunact Cancer Institute Pvt. Ltd.
Thane, India
Regional Cancer Centre Thiruvananthapuram
Thiruvananthapuram, India
Tata Memorial Centre - Mahamana Pandit Madan Mohan Malaviya Cancer Centre
Varanasi, India
Cork University Hospital
Cork, Ireland
Beaumont Hospital
Dublin, Ireland
Mater Misericordiae University Hospital
Dublin, Ireland
Tallaght University Hospital
Dublin, Ireland
Azienda Ospedaliera San Giuseppe Moscati
Avellino, Italy
Centro di Riferimento Oncologico (CRO)
Aviano, Italy
Istituto per la Ricerca e la Cura del Cancro (IRCC) - Istituto di Candiolo
Candiolo, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Istituto Nazionale Tumori (INT) "Fondazione G. Pascale" di Napoli
Naples, Italy
Azienda Ospedaliera di Perugia - Ospedale Santa Maria della Misericordia
Perugia, Italy
Arcispedale Santa Maria Nuova
Reggio Emilia, Italy
Azienda Ospedaliera Santa Maria di Terni
Terni, Italy
Latvian Oncology Center
Riga, Latvia
Paula Stradiņa Klīniskā Universitātes Slimnīca
Riga, Latvia
Hospital of Lithuanian University of Health Sciences Kauno Klinikos
Kaunas, Lithuania
Nacionalinis Vezio Institutas
Vilnius, Lithuania
Hospital Tengku Ampuan Afzan
Kuantan, Malaysia
Hospital Umum Sarawak - Clinical Research Centre
Kuching, Malaysia
Gleneagles Medical Centre - Penang
Pulau Pinang, Malaysia
Hospital Pulau Pinang
Pulau Pinang, Malaysia
Szpital Morski im. PCK (Maritime Hospital) (Gdynskie Centrum Onkologii)
Gdynia, Poland
Przychodnia Lekarska "KOMED"
Konin, Poland
Instytut Medyczny Santa Familia Sp. z o. o. w Łodzi
Lodz, Poland
IP Clinic Sp. z o.o.
Lodz, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie
Warsaw, Poland
Hospital Garcia de Orta, EPE
Almada, Portugal
Hospital CUF Descobertas
Lisbon, Portugal
Hospital Lusíadas Lisboa
Lisbon, Portugal
Unidade Local de Saude de Santa Maria, EPE - Hospital Pulido Valente
Lisbon, Portugal
Unidade Local de Saude de Loures - Odivelas, E. P. E.
Loures, Portugal
Instituto Português Oncologia do Porto Francisco Gentil, EPE
Porto, Portugal
Centrul Medical Medicover Victoria
Bucharest, Romania
Spitalul Memorial Healthcare International
Bucharest, Romania
Onco Clinic Consult SA
Craiova, Romania
OncoLab
Craiova, Romania
Victoria Hospital - Centrul de Oncologie Euroclinic SRL
Iași, Romania
Ovidius Clinical Hospital S.R.L.
Ovidiu, Romania
Hospital Universitari Germans Trias i Pujol
Badalona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Universitario Vall d'Hebron
Barcelona, Spain
Instituto Oncologico Dr. Rosell - Hospital Universitari Quiron Dexeus Location
Barcelona, Spain
Hospital Universitario Reina Sofía
Córdoba, Spain
HM Universitario Sanchinarro
Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Hospital Regional Universitario de Málaga - Hospital General
Málaga, Spain
Hospital Universitario Central de Asturias
Oviedo, Spain
Parc Tauli Hospital Universitari
Sabadell, Spain
Hospital Universitario Virgen Macarena
Seville, Spain
Hospital Clinico Universitario de Valencia
Valencia, Spain
Hospital Clínico Universitario "Lozano Blesa"
Zaragoza, Spain
Phramongkutklao Hospital
Bangkok, Thailand
Faculty of Medicine Vajira Hospital
Dusit, Thailand
Prince of Songkhla University
Hat Yai, Thailand
Adana Medical Park Seyhan Hospital
Adana, Turkey (Türkiye)
Adana Sehir Training and Research Hospital
Adana, Turkey (Türkiye)
Ankara Universitesi Tip Fakultesi Hastaneleri - Cebeci Hastanesi
Ankara, Turkey (Türkiye)
Gulhane Egitim ve Arastirma Hastanesi
Ankara, Turkey (Türkiye)
Hacettepe Universitesi Kanser Enstitusu (Hacettepe University Cancer Institute)
Ankara, Turkey (Türkiye)
Uludağ Üniversitesi Tıp Fakültesi
Bursa, Turkey (Türkiye)
Istanbul Oncology Hospital
Cevizli, Turkey (Türkiye)
Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi Hastane
Edirne, Turkey (Türkiye)
Bahcelievler Memorial Hospital
Istanbul, Turkey (Türkiye)
T.C. S.B. Prof. Dr. Suleyman Yalcin Sehir Hastanesi
Istanbul, Turkey (Türkiye)
Sakarya Universitesi Tıp Fakultesi Dekanligi
Sakarya, Turkey (Türkiye)
University Hospitals Birmingham NHS Foundation Trust - New Queen Elizabeth Hospital Birmingham
Birmingham, United Kingdom
The Royal Surrey County Hospital NHS Foundation Trust
Guildford, United Kingdom
The Christie NHS Foundation Trust - Christie Hospital
Manchester, United Kingdom
Related Publications (1)
O'Byrne K, Esteban E, Lee CL, Hegmane A, Volovat C, Lo Russo G, Ziogas D, Atmaca A, Sebastian M, Majem M. A phase III placebo-controlled study of eftilagimod alfa plus pembrolizumab and chemotherapy in metastatic non-small cell lung cancer. Future Oncol. 2025 Dec;21(30):3885-3890. doi: 10.1080/14796694.2025.2597404. Epub 2025 Dec 12.
PMID: 41383151DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 3, 2024
First Posted
December 10, 2024
Study Start
March 21, 2025
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
September 1, 2029
Last Updated
March 18, 2026
Record last verified: 2025-11