Clinical trial NCT06726265: 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)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)
Lead sponsor: Immutep S.A.S.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-12-10
Enrollment: 756
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: TACTI-004 is a double-blinded, randomized phase 3 trial in patients with advanced/metastatic non-small cell lung cancer (NSCLC) receiving eftilagimod alfa (major histocompatibility complex (MHC) class II agonist) in combination with pembrolizumab (programmed cell death protein 1 (PD-1) antagonist) and chemotherapy.

The proposed clinical trial aims to compare the efficacy and to demonstrate the superiority of efti combined with standard of care (SoC, pembrolizumab and histology-based chemotherapy) compared to placebo combined with SoC in programmed death-ligand 1 (PD-L1) unselected population as assessed by:

* Overall survival \[OS\]
* Progression-free survival \[PFS\] per RECIST 1.1

The trial is planned to be conducted in countries in Asia, Australia, Europe and North and South America in approximately 175 experienced clinical sites.

Eligibility criteria: Inclusion Criteria

Participants may be enrolled if they meet all of the following criteria at screening:

1. Willing to give written informed consent and to comply with the protocol.
2. 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.
3. 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.
4. 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).
5. Be ≥ 18 years of age on the day of signing the informed consent.
6. Participants capable of producing sperm 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.
7. 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.
8. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization.
9. Expected survival \> 3 months.
10. Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by site.
11. 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.
12. 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.
13. 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.
14. 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.
15. Human immunodeficiency virus (HIV) infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease.
16. Adequate organ function.

Exclusion Criteria

Participants are to be excluded from the trial at the time of screening for any of the following reasons:

1. 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).
2. Received prior radiotherapy within 2 weeks of start of trial intervention, or has radiation-related toxicities, requiring corticosteroids.
3. Participants whose tumor harbors any of the following actionable molecular alterations:

   1. Epidermal growth factor receptor (EGFR)-sensitizing (activating) mutation
   2. Anaplastic lymphoma kinase (ALK) gene fusion positive (ALK translocation)
   3. c-ROS oncogene 1 (ROS1) translocation
4. For any indication has received any of the following therapies

   1. 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, radiation therapy or had major surgery;
   2. 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;
   3. within 6 months prior to cycle1 day 1 received lung radiation therapy of \>30 Gray (Gy).
5. 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.
6. 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.
7. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
8. 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.
9. Active infection requiring parenteral systemic therapy within 4 weeks prior to cycle 1 day 1 and/or significant acute or chronic infection in screening and/or on cycle 1 day 1.
10. Evidence of severe or uncontrolled cardiac disease within 6 months prior to first dose of trial treatment including: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 5.0 Grade ≥ 2, atrial fibrillation \> Grade 2 not controlled by a pacemaker, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association (NYHA) III-IV), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
11. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
12. Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
13. 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 trial intervention.
14. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
15. HIV-infected patients with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
16. History of allogenic tissue/solid organ transplant.
17. Known additional malignancy that is progressing or has required active treatment within the past 3 years.
18. Has hypersensitivity to eftilagimod alfa and/or pembrolizumab (≥Grade 3) and/or any of its excipients.
19. Has hypersensitivity to any component of planned platinum-based doublet chemotherapy and/or any of its excipients.
20. Received a live or live-attenuated vaccine within 30 days before the first dose of trial intervention. Administration of killed vaccines is allowed
21. Has a life-threatening illness unrelated to cancer.
22. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.

Primary outcomes:
measure: Determination of Overall survival (OS)
timeFrame: Up to approximately 54 months
measure: Determination of Progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 54 months
Secondary outcomes:
measure: Determination of Objective response rate (ORR) per RECIST 1.1
timeFrame: Up to approximately 54 months
measure: Frequency of adverse events (AEs)
timeFrame: Up to approximately 27 months
measure: Severity of adverse events (AEs) according to the United States National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v5.0
timeFrame: Up to approximately 27 months
measure: Determination of Time to Response (TTR) by RECIST 1.1.
timeFrame: Up to approximately 54 months
measure: Determination of Duration of Response (DOR) by RECIST 1.1.
timeFrame: Up to approximately 54 months
measure: Determination of PFS on next line therapy (PFS2)
timeFrame: Up to approximately 54 months
Other outcomes:
Locations:
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
city: Greenslopes
country: Australia
facility: Greenslopes Private Hospital
city: Southport
country: Australia
facility: Tasman Oncology Research Ltd
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
city: Wollongong
country: Australia
facility: Cancer Care Wollongong Pty Limited
city: Gent
country: Belgium
facility: Algemeen Ziekenhuis Maria Middelares
city: Namur
country: Belgium
facility: Clinique et Maternité Sainte-Elisabeth
city: Dobrich
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Dobrich AD
city: Panagyurishte
country: Bulgaria
facility: MHAT Uni Hospital OOD
city: Ruse
country: Bulgaria
facility: Complex Oncology Center Ruse
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Serdika EOOD
city: Brampton
country: Canada
facility: Brampton Civic Hospital
city: St-Jerome
country: Canada
facility: Unite de recherche clinique du CISSS des Laurentides
city: Osijek
country: Croatia
facility: Klinički Bolnički Centar Osijek
city: Piraeus
country: Greece
facility: Metropolitan Hospital, Department of Oncology
city: Thessaloniki
country: Greece
facility: Bioclinic of Thessaloniki
city: Thessaloniki
country: Greece
facility: Interbalkan Medical Center of Thessaloniki
city: Thane
country: India
facility: Sunact Cancer Institute Pvt. Ltd.
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico (CRO)
city: Candiolo
country: Italy
facility: Istituto per la Ricerca e la Cura del Cancro (IRCC) - Istituto di Candiolo
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori (INT) "Fondazione G. Pascale" di Napoli
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Riga
country: Latvia
facility: Latvian Oncology Center
city: Riga
country: Latvia
facility: Paula Stradiņa Klīniskā Universitātes Slimnīca
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno Klinikos
city: Vilnius
country: Lithuania
facility: Nacionalinis Vezio Institutas
city: Lodz
country: Poland
facility: Instytut Medyczny Santa Familia Sp. z o. o. w Łodzi
city: Lodz
country: Poland
facility: IP Clinic Sp. z o.o.
city: Lisboa
country: Portugal
facility: Unidade Local de Saude de Santa Maria, EPE - Hospital Pulido Valente
city: Bucharest
country: Romania
facility: Centrul Medical Medicover Victoria
city: Bucharest
country: Romania
facility: Spitalul Memorial Healthcare International
city: Craiova
country: Romania
facility: Onco Clinic Consult SA
city: Iasi
country: Romania
facility: Victoria Hospital - Centrul de Oncologie Euroclinic SRL
city: Ovidiu
country: Romania
facility: Ovidius Clinical Hospital S.R.L.
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: HM Universitario Sanchinarro
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Málaga - Hospital General
city: Sabadell
country: Spain
facility: Parc Tauli Hospital Universitari
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario "Lozano Blesa"
Study officials:
References: