| CTRI Number |
CTRI/2025/03/082306 [Registered on: 13/03/2025] Trial Registered Prospectively |
| Last Modified On: |
15/06/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Biological
Other (Specify) [Placebo] |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
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) |
|
Scientific Title of Study
|
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. |
| Trial Acronym |
TACTI-004 (IMP321-P026) ; Keynote-F91 |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2024-513621-23-00 |
EudraCT |
| TACTI-004, version 1.1 dated 06 Sep 2024 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Shekhar Dawkhar |
| Designation |
Senior Director |
| Affiliation |
Fortrea Development India Private Limited |
| Address |
Fortrea Development India Private Limited,Building No.1, Unit No. 601, Raheja Mindspace, Plot Nos. Gen,2,1, D-F at MIDC Trans Thane Creek Industrial Area, Shiravane
Mumbai (Suburban)
MAHARASHTRA
400706
India |
| Phone |
7506653414 |
| Fax |
|
| Email |
Shekhar.Dawkhar@fortrea.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Shekhar Dawkhar |
| Designation |
Senior Director |
| Affiliation |
Fortrea Development India Private Limited |
| Address |
Fortrea Development India Private Limited,Building No.1, Unit No. 601, Raheja Mindspace, Plot Nos. Gen,2,1, D-F at MIDC Trans Thane Creek Industrial Area, Shiravane
MAHARASHTRA
400706
India |
| Phone |
7506653414 |
| Fax |
|
| Email |
Shekhar.Dawkhar@fortrea.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Shekhar Dawkhar |
| Designation |
Senior Director |
| Affiliation |
Fortrea Development India Private Limited |
| Address |
Fortrea Development India Private Limited,Building No.1, Unit No. 601, Raheja Mindspace, Plot Nos. Gen,2,1, D-F at MIDC Trans Thane Creek Industrial Area, Shiravane
MAHARASHTRA
400706
India |
| Phone |
7506653414 |
| Fax |
|
| Email |
Shekhar.Dawkhar@fortrea.com |
|
|
Source of Monetary or Material Support
|
| Fortrea Development India Private Limited,Building No. 1, Unit No.601,Raheja Mindspace, Plot Nos.Gen/2/1/D/E/F at MIDCTTC Industrial Area,Shiravane,Nerul,Navi Mumbai, Maharashtra,400706,India |
|
|
Primary Sponsor
|
| Name |
Immutep S.A.S. |
| Address |
Parc Les Algorithmes,Bâtiment 7- Le Pythagore, Route de l’Orme - RD128
91190 SAINT-AUBIN, France |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Fortrea Development India Private Limited Building No Unit No Raheja Mindspace |
Fortrea Development India Private Limited, Building No. 1, Unit No. 601, Raheja Mindspace
Plot Nos. Gen,2,1, D-F at MIDC Trans Thane Creek Industrial Area, Shiravane |
|
|
Countries of Recruitment
|
Argentina
Australia
Austria
Belgium
Brazil
Canada
Chile
Croatia
Georgia
Germany
Greece
Hungary
India
Ireland
Italy
Latvia
Lithuania
Malaysia
Mexico
Poland
Portugal
Romania
Spain
Turkey
United Kingdom
United States of America
Bulgaria |
Sites of Study
Modification(s)
|
| No of Sites = 10 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sandip Kumar Barik |
All India Institute of Medical Sciences |
Dept. of Radiation Oncology,Sijua, Patrapada, Bhubaneswar-751019
Khordha
ORISSA |
9450381454
sandip.barik1@gmail.com |
| Dr Swaminathan Ganapathi Raman |
Cancare Foundation The Voluntary Health Services |
SH,49A,Pallipattu,Taramani,Chennai-600113
Chennai
TAMIL NADU |
9025260160
crrt.onco@gmail.com |
| Dr Kalyan Kusum Mukherjee |
Chittaranjan National Cancer Institute |
37 S.P. Mukherjee Road, Kolkata-700026
Kolkata
WEST BENGAL |
033 24759313
kkmukherjee@cnci.org.in |
| Dr Rejiv Rajendranath |
Geri Care Hospitals |
No 8, Dr Nair Road, T Nagar, Chennai 600017
Chennai
TAMIL NADU |
9840978491
rejivr@yahoo.co.in |
| Dr Govind Babu |
Healthcare Global Enterprises Limited |
8, HCG Towers, P Kalinga Rao Road, Sampangi Ram Nagar, Bangalore 560027
Bangalore
KARNATAKA |
9845072940
kglaugh@gmail.com |
| Dr Bipinesh Sansar |
Mahamana Pandit Madan Mohan Malaviya Cancer Centre |
Department of Medical Oncology,OPD No:29, Ground Floor,DNT Block,Sundar Bagiya, Near Nariya Gate, Banaras Hindu University Campus
Varanasi
UTTAR PRADESH |
8002583913
Bipinesh04@yahoo.co.in |
| Dr Mohammad Azam |
Maulana Azad Medical College Associated Lok Nayak Hospital |
2, Bahadur Shah Zafar Marg, New Delhi 110002
New Delhi
DELHI |
7080178424
drazamdelhi@gmail.com |
| Dr Sandeep Kumar Jasuja |
R.K. Birla Cancer Centre, SMS Medical College and Hospital |
Jawahar Lal Nehru Marg, Jaipur, 302004
Jaipur
RAJASTHAN |
9660121475
sandeepjasuja99@gmail.com |
| Dr Anoop TM |
Regional Cancer Centre |
Medical College Campus, Trivandrum, Kerala - 695011
Thiruvananthapuram
KERALA |
9447134973
dranooptm@gmail.com |
| Dr Vijay Maruti Patil |
Sunact Cancer Institute |
4th floor, Tieten Medicity, Kasarvadavali, Ghodbunder road,Thane (W.)- 400615
Thane
MAHARASHTRA |
8655313412
vijaypgi@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 10 |
| Name of Committee |
Approval Status |
| Ethics Committee S.M.S. Medical College and Attached Hospitals |
Submittted/Under Review |
| HCG Central Ethics Committee |
Approved |
| Human Ethics Committee RCC |
Submittted/Under Review |
| IEC - Geri Care Hsopitals |
Approved |
| Institutional Ethics Committee Chittaranjan National Cancer Institute |
Approved |
| INSTITUTIONAL ETHICS COMMITTEE MAMC, MAULANA AZAD MEDICAL COLLEGE |
Submittted/Under Review |
| Institutional Ethics Committee The Voluntary Health Services |
Submittted/Under Review |
| Institutional Ethics Committee, AIIMS |
Submittted/Under Review |
| Instiutional ethics committee MPMMCC & HBCH |
Submittted/Under Review |
| Vedant Hospital Institutional Ethical Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
efti + Standard of Care arm
Combination of efti, pembrolizumab (KEYTRUDA®) and histology-based platinum doublet chemotherapy |
Biological: eftilagimod alfa (other names: IMP321, LAG-3Ig, efti, eftilagimod alpha), 30 mg of efti every 2 weeks subcutaneously for the first 6 months, thereafter every 3 weeks for up to 24 months in total
/// Biological: Pembrolizumab (KEYTRUDA®) 200 mg pembrolizumab (KEYTRUDA®) every 3 weeks i.v. for up to approximately 24 months
/// Drug: carboplatin plus paclitaxel: For patients 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
/// Drug: cisplatin or carboplatin + pemetrexed For patients 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
|
| Comparator Agent |
Placebo Comparator: Placebo + Standard of Care arm
Combination of efti-matching placebo, pembrolizumab (KEYTRUDA®) and histology-based platinum doublet chemotherapy |
Placebo: efti-matching placebo every 2 weeks subcutaneously for the first 6 months, thereafter every 3 weeks for up to 24 months in total
/// Biological: Pembrolizumab (KEYTRUDA®), 200 mg pembrolizumab (KEYTRUDA®) every 3 weeks i.v. for up to approximately 24 months
/// Drug: carboplatin plus paclitaxel: For patients 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
/// Drug: cisplatin or carboplatin + pemetrexed: For patients 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
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
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 greater than or equal to 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 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 greater than 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 less than or equal to Grade 1 or baseline. Participants with CTCAE less than or equal to 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.
|
|
| ExclusionCriteria |
| Details |
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:
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
4.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, radiation 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 cycle1 day 1 received lung radiation therapy of greater than 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).
Note: Prior treatment with an anti-PD-1, anti-PD-Ll, 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 greater than or equal to 2, atrial fibrillation greater than 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 (Greater than or equal to 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. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
Overall survival
Progression-free survival per RECIST 1.1
|
Up to approximately 54 months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Objective response rate as per RECIST 1.1 |
Up to approximately 54 months |
| Adverse events (AEs), vital signs, physical examinations, 12-lead electrocardiograms (ECGs), and safety laboratory assessments |
Up to approximately 27 months |
| Time to response (TTR) |
Up to approximately 54 months |
| Duration of Response (DOR) |
Up to approximately 54 months |
| Progression-free survival on next line therapy (PFS2) |
Up to approximately 54 months |
|
|
Target Sample Size
|
Total Sample Size="756"
Sample Size from India="58"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
31/03/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
31/03/2025 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="4"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
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). The trial has a double-blind, randomized design. Subjects will be randomized 1:1 to receive either combination of efti, pembrolizumab and histology-based platinum doublet chemotherapy (E+SoC arm) or efti-matching placebo plus pembrolizumab in combination with histology-based platinum doublet chemotherapy (Placebo+SoC arm). |