Phase 3 Randomized Trial of Eftilagimod Alfa, Pembrolizumab, and Chemotherapy in Advanced/Metastatic Non-Small Cell Lung Cancer Patients
- Trial ID
- 2024-513621-23-00
- Protocol
- TACTI-004
- Sponsor
- Immutep
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **efficacy** of eftilagimod alfa (efti) combined with pembrolizumab and chemotherapy against the standard of care (SoC) in a PD-L1 unselected population of patients with advanced/metastatic non-small cell lung cancer (NSCLC). This objective is clinically relevant as it aims to determine whether the combination therapy can provide superior outcomes in terms of tumor response and patient survival compared to existing treatment protocols.
Secondary objectives include:
- Evaluating the objective response rate (ORR) based on RECIST 1.1 in patients treated with efti combined with pembrolizumab and chemotherapy compared to SoC.
- Examining the safety and tolerability of efti in combination with pembrolizumab and chemotherapy compared to SoC.
- Assessing disease control rate (DCR), time to response (TTR), and duration of response (DOR) by RECIST 1.1.
- Assessing time to next treatment (TTNT).
- Assessing changes in health-related quality of life (QoL) assessments from baseline in patients treated with efti combined with pembrolizumab and chemotherapy compared to SoC.
- Assessing progression-free survival (PFS) on next line therapy (PFS2).
Participants
The clinical trial involves a total of **393 participants** diagnosed with **advanced/metastatic non-small cell lung cancer (NSCLC)**. The study population includes both male and female subjects, aged 18 years and older, who are part of a vulnerable population. Participants were selected based on their ability to provide informed consent and compliance with the protocol, as well as having a histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC. The trial does not restrict participation based on gender, and both males and females are included. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population is characterized by their general health status, which includes adequate organ function and recovery from any adverse events related to previous anticancer therapies. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to specific contraceptive guidelines if capable of reproduction. The trial does not provide additional information on specific lifestyle habits or dietary restrictions.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of **eftilagimod alfa** in combination with **pembrolizumab** and chemotherapy in patients with advanced/metastatic non-small cell lung cancer (NSCLC). The trial aims to compare this combination therapy against the standard of care in a PD-L1 unselected population. The study is expected to commence recruitment on April 1, 2025, and conclude by August 31, 2029, with a maximum treatment period of 103 weeks for the investigational products.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as measurable disease, recovery from previous therapies, and adequate organ function. Following randomization, participants will receive treatment and attend regular follow-up visits to monitor efficacy and safety outcomes. These visits will include assessments of overall survival, progression-free survival, and response rates according to RECIST 1.1 criteria. Safety evaluations will encompass adverse event monitoring, vital signs, physical examinations, ECGs, and laboratory assessments.
The end-of-study visit will occur after the completion of the treatment period or upon early termination. Participants may be withdrawn from the study if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The expected length of participant involvement is up to 103 weeks, with conditions for early termination including non-compliance with the protocol or adverse events that compromise safety. The trial will ensure that all procedures adhere to ethical standards and regulatory requirements, maintaining the integrity and scientific validity of the study.
Treatment
The clinical trial involves the administration of several experimental and non-experimental treatments. **Pemetrexed Fresenius Kabi** is a concentrate for solution for infusion, containing the active substance **pemetrexed**. It is administered via **intravenous infusion** at a dosage of 500 mg/m², with a maximum total dose of 17,500 mg/m² over a treatment period of 103 weeks. The pharmaceutical form is a solution for infusion, and the product is manufactured by Fresenius Kabi Deutschland GmbH.
**KEYTRUDA** (pembrolizumab) is another experimental treatment used in the trial. It is a concentrate for solution for infusion, administered via intravenous infusion. The dosage is 200 mg, with a maximum total dose of 7,000 mg over 103 weeks. Pembrolizumab is a protein-based substance, and the product is manufactured by Merck Sharp & Dohme B.V.
**IMP321** (eftilagimod alfa) is administered as a solution for injection via subcutaneous use. The dosage is 30 mg, with a maximum total dose of 1,170 mg over 103 weeks. Eftilagimod alfa is a protein-based substance, and the product is manufactured by Immutep S.A.S.
**Carboplatin** is used as a non-experimental treatment in the trial. It is a concentrate for solution for infusion, administered via intravenous infusion. The dosage is 870 mg, with a maximum total dose of 3,480 mg over a treatment period of 12 weeks. Carboplatin is a chemical-based substance.
**Paclitaxel** is another non-experimental treatment, administered as a concentrate for solution for infusion via intravenous infusion. The dosage is 200 mg/m², with a maximum total dose of 800 mg/m² over 12 weeks. Paclitaxel is a chemical-based substance.
**Cisplatin** is also used as a non-experimental treatment. It is a concentrate for solution for infusion, administered via intravenous infusion. The dosage is 75 mg/m², with a maximum total dose of 300 mg/m² over 12 weeks. Cisplatin is a chemical-based substance.
An **Efti-matching placebo** is included in the trial to match the appearance and injection characteristics of eftilagimod alfa but does not contain any active substance. It serves as a control to evaluate the efficacy of the experimental treatments.
Efficacy
The efficacy of the clinical trial will be assessed using a combination of primary and secondary endpoints. The primary endpoints include **Overall Survival (OS)**, defined as the time from randomization to death from any cause, and Progression-Free Survival (PFS) as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). PFS is defined as the time from randomization to documented disease progression or death from any cause, as assessed by the Investigator based on RECIST.
Secondary endpoints will include the Objective Response Rate (ORR) according to RECIST 1.1, defined as the proportion of patients achieving a best overall confirmed response of complete response (CR) or partial response (PR). Additional secondary endpoints encompass the Disease Control Rate (DCR), Duration of Response (DOR), Time to Response (TTR), and Time to Next Treatment (TTNT). Changes from baseline in Quality of Life (QoL) will be evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30), EORTC QLQ-LC13, and EuroQol 5 Dimension 5 Level (EQ-5D-5L). PFS2, defined as the time from randomization to disease progression or death on next-line treatment, will also be assessed.
The frequency, severity, and duration of adverse events (AEs), along with clinically relevant abnormalities in vital signs, physical examinations, 12-lead electrocardiograms (ECGs), and safety laboratory assessments, will be monitored. These efficacy parameters will be measured and collected at specified timepoints throughout the trial, ensuring a comprehensive evaluation of the treatment's impact on patients with advanced/metastatic non-small cell lung cancer (NSCLC).
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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) 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 (previous palliative radiotherapy for advanced/metastatic disease acceptable).
- 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 PD-L1 biomarker result from central laboratory, using the FDA approved Dako standardized diagnostic test (PD-L1 IHC 22C3 pharmDx).
- Be ≥ 18 years of age on the day of signing the informed consent.
- If assigned male at birth, the participant agrees to the following during the intervention period and for at least the time needed to eliminate the following interventions after the last dose of the specified trial intervention. The length of time required to continue contraception for trial interventions is: • cisplatin: 100 days • carboplatin: 100 days • pemetrexed: 100 days • paclitaxel: 100 days - Refrains from donating sperm PLUS either: - Abstains from intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR - Uses a penile/external condom when having intercourse PLUS partner of childbearing potential who is not currently pregnant should use an additional contraceptive method (refer to Protocol Section 5.13), as a condom may break or leak. - Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials. If the contraception requirements in the local label for any of the trial interventions are more stringent than the requirements above, the local label requirements are to be followed.
- A participant of childbearing potential (POCBP) is eligible to participate if not pregnant and a negative pregnancy test before the first dose of trial intervention has been obtained. Additional requirements for pregnancy testing during and after trial intervention are in Contraception Methods. - A POCBP is eligible to participate if not breastfeeding during the trial intervention period and as defined in the protocol. - A POCBP is eligible to participate if a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency is used, or penile-vaginal intercourse abstinence, as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), is adhered to as described in Protocol Section 5.13 during the intervention period and for at least the time needed to eliminate each trial intervention after the last dose of trial intervention. In addition, the participant agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of reproduction. The length of time required to continue contraception for each trial intervention is defined in the protocol.
- An ECOG performance status of 0 to 1 assessed within 7 days before randomization.
- Expected survival > 3 months.
- Evidence of measurable disease as defined by 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. Note: Participants must have completed curative antiviral therapy at least 4 weeks prior to randomization.
- Human immunodeficiency virus (HIV) infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as: a. Participants on ART must have a CD4+ T-cell count > 350 cells/mm3 at time of screening. b. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening. c. Participants on ART must have been on stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to cycle 1 day 1. d. It is advised that participants must not have had any acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 12 months. e. The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates.
- Adequate organ function as defined in the protocol. Specimens must be collected within 10 days before randomization.
Exclusion Criteria
- 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: a. epidermal growth factor receptor (EGFR)-sensitizing (activating) mutation; b. anaplastic lymphoma kinase (ALK) gene fusion positive (ALK translocation); c. c-ROS oncogene 1 (ROS1) translocation.
- For any indication has received any of the following therapies: a. 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; b. 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; c. within 6 months prior to cycle 1 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., CTLA-4, OX 40, CD137) or lymphocyte activation gene 3 (LAG-3) targeting therapy (e.g., anti-LAG-3 antibodies). Note: 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. Note: Participants with available neuroimaging performed as routine clinical management before the Screening imaging may be enrolled using this exception and compared to the imaging conducted at Screening.
- 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.
- 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 (NYHA III-IV), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
- History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- 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.
- 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.
- 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.
- HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
- History of allogenic tissue/solid organ transplant.
- Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- Has hypersensitivity to eftilagimod alfa and/or pembrolizumab (≥Grade 3) and/or any of its excipients.
- Has hypersensitivity to any component of planned platinum-based doublet chemotherapy and/or any of its excipients.
- Received a live or live-attenuated vaccine within 30 days before the first dose of trial intervention. Administration of killed vaccines is allowed. Refer to Protocol Section 5.10 for information on COVID-19 vaccines.
- Has a life-threatening illness unrelated to cancer.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 01 Apr 2025 | 16 |
 Belgium | Not Recruiting | 01 Apr 2025 | 9 |
 Bulgaria | Not Recruiting | 01 Apr 2025 | 24 |
 Croatia | Not Recruiting | 01 Apr 2025 | 18 |
 Germany | Not Recruiting | 01 Apr 2025 | 52 |
 Greece | Not Recruiting | 01 Apr 2025 | 29 |
 Hungary | Not Recruiting | 01 Apr 2025 | 17 |
 Ireland | Not Recruiting | 01 Apr 2025 | 11 |
 Italy | Not Recruiting | 01 Apr 2025 | 36 |
 Latvia | Not Recruiting | 01 Apr 2025 | 13 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 200 | 103 | PRD4323785 |
PACLITAXEL | Test | — | INTRAVENOUS INFUSION | 200 | 12 | SUB09583MIG |
CISPLATIN | Test | — | INTRAVENOUS INFUSION | 75 | 12 | SUB07483MIG |
CARBOPLATIN | Test | — | INTRAVENOUS INFUSION | 870 | 12 | SUB06614MIG |
Pemetrexed Fresenius Kabi 25 mg/ml concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 500 | 103 | PRD7936183 |
IMP321 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 30 | 103 | PRD3124166 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 200 | 103 | PRD4323784 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 200 | 103 | PRD4323786 |
Efti-matching placebo (placebo is matching the appearance and injection characteristics of efti but does not contain active substance). | Placebo | N/A | — | — | — | N/A |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 200 | 103 | PRD4323105 |