First Patient Dosed in Immutep’s TACTI-004 Phase III Trial in First Line Non-Small Cell Lung Cancer

Rhea-AI Summary

Immutep (NASDAQ: IMMP) has initiated its pivotal TACTI-004 Phase III trial with the first patient successfully dosed at Calvary Mater Newcastle Hospital in Australia. The trial will evaluate eftilagimod alfa, a first-in-class MHC Class II agonist, in combination with KEYTRUDA® and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC).

The global study will enroll approximately 756 patients across more than 150 clinical sites. The trial has received regulatory approvals in 16 countries, including Australia, Canada, and several European nations, with additional clearances expected soon. The 30mg subcutaneous efti dosing will be used, based on previous regulatory discussions and demonstrated efficacy.

NSCLC represents 80-85% of all lung cancer diagnoses, with less than 30% survival rate after five years. The trial results will support a potential marketing approval application in NSCLC, one of the largest oncology indications.

Positive

• First patient successfully dosed in pivotal Phase III trial, marking significant milestone
• Large-scale trial with 756 patients across 150+ clinical sites indicates robust study design
• Already received regulatory approvals in 16 countries with more pending
• Targets NSCLC, one of the largest oncology market opportunities
• Previous trials showed strong efficacy across all PD-L1 levels with favorable safety profile

Negative

• Selected lower 30mg dose due to tolerability issues at 90mg
• Faces competition in established NSCLC treatment landscape
• Trial results and potential marketing approval still pending with no guaranteed success

Insights

Oncology Clinical Development Expert

The initiation of the TACTI-004 Phase III trial represents a significant advancement in Immutep's clinical program for eftilagimod alfa (efti). This pivotal trial targeting first-line non-small cell lung cancer has begun patient dosing, with plans to enroll 756 patients across 150+ clinical sites globally.

The trial design evaluates a novel triple combination approach: efti (a first-in-class MHC Class II agonist) with pembrolizumab (KEYTRUDA, an anti-PD-1 therapy) and chemotherapy. What makes this particularly noteworthy is efti's mechanism of action, which has shown efficacy across all PD-L1 expression levels in previous studies - a crucial differentiator in lung cancer treatment where PD-L1 status often determines therapy selection.

The company has settled on the 30mg subcutaneous dosing regimen following regulatory discussions, including with the FDA under Project Optimus, after tolerability issues at higher doses. This conservative approach prioritizes safety while maintaining efficacy based on earlier promising clinical data.

If successful, this trial could establish a new standard-of-care in NSCLC, which remains the leading cause of cancer death globally. With NSCLC accounting for 80-85% of lung cancer cases and less than 30% five-year survival rates, the unmet need is substantial. The extensive global regulatory approvals for site activation indicate strong interest in this potential therapeutic approach and suggest confidence in the preliminary data.

Biotechnology Investment Analyst

Dosing the first patient in TACTI-004 is a pivotal milestone for Immutep that significantly de-risks their clinical development pathway. This Phase III trial positions efti for potential regulatory submission in non-small cell lung cancer - one of oncology's largest commercial markets.

The company has secured impressive global regulatory clearances across 16 countries already (including major markets like the UK, Germany, Canada, and Australia), with additional approvals expected shortly. This broad geographic distribution helps mitigate enrollment risks and demonstrates regulatory confidence in the program's safety profile.

The trial targets first-line NSCLC treatment, the most valuable position in the treatment paradigm. Crucially, previous data suggests efti works regardless of PD-L1 expression levels, potentially addressing a broader patient population than some competing therapies that work optimally only in PD-L1 high expressors.

Immutep's partnership with MSD (Merck) for this combination approach with KEYTRUDA provides validation from one of oncology's leading players. KEYTRUDA generated over $20 billion in annual sales, and combinations that enhance its efficacy represent significant commercial opportunities.

While Immutep must now execute a complex global trial, the company has positioned itself with the appropriate dosing regimen (30mg) that balances efficacy and safety. The trial's success could transform Immutep from a clinical-stage biotech into a commercial entity with a therapy addressing a market affecting approximately 3 million patients worldwide by 2030.

• First patient safely dosed at Calvary Mater Newcastle Hospital in Australia, marking a significant milestone for Immutep
• Global Phase III with efti will enrol approximately 756 patients at more than 150 clinical sites
• Trial results will inform potential marketing approval application in non-small cell lung cancer, one of the largest indications in oncology
  
  

 SYDNEY, AUSTRALIA, March 25, 2025 (GLOBE NEWSWIRE) --  Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a late-stage immunotherapy company targeting cancer and autoimmune diseases, today announces the first patient has been successfully dosed in the Company’s pivotal TACTI-004 Phase III trial. TACTI-004 will evaluate Immutep’s eftilagimod alfa, a first-in-class MHC Class II agonist, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) and chemotherapy as first line treatment for patients with advanced or metastatic non-small cell lung cancer (1L NSCLC).

Dr. Ina Nordman, who treated the first patient at Calvary Mater Newcastle Hospital in Australia, stated, “We are very excited to participate in this important Phase III trial. Despite advancements in the treatment landscape for non-small cell lung cancer, there remains a high unmet need for new approaches that can safely extend patients’ lives. The anti-cancer immune response driven by efti’s unique mechanism of action as an MHC Class II agonist in combination with KEYTRUDA has led to strong efficacy across all PD-L1 levels with favourable safety in multiple lung cancer trials. We hope to see this study confirm the promise of this novel combination to provide patients with a powerful new treatment option.”

Immutep CEO, Marc Voigt, said, “Dosing the first patient in our pivotal Phase III trial ranks among the most significant milestones in the Company’s history. We are excited about the potential of the TACTI-004 study to deliver a new standard-of-care therapy for patients with metastatic or advanced non-small cell lung cancer that includes efti in combination with KEYTRUDA. If successful, the study will result in a clinically meaningful and statistically improved survival benefit and thus could potentially be practice changing.”

Immutep CSO, Frédéric Triebel, M.D., Ph.D, commented, “As a result of all global regulatory interactions to date including previous discussion with US FDA under Project Optimus and tolerability issues at 90 mg¹, we are moving forward with 30 mg subcutaneous efti dosing used in previous studies. The ability of 30 mg efti in combination with KEYTRUDA to activate the immune system and fight non-small cell lung cancer regardless of PD-L1 expression has been demonstrated across multiple clinical trials.² Importantly, this novel approach has an excellent safety profile while delivering strong efficacy that compares favourably to standard-of-care therapies, including high rates of durable responses and compelling progression-free survival and overall survival.”

Recruitment in TACTI-004 is underway at a growing number of activated clinical sites and countries with approvals from all regulatory authorities continues to expand including Australia, Austria, Belgium, Bulgaria, Canada, Germany, Greece, Hungary, India, Ireland, Italy, Latvia, Lithuania, Portugal, Spain, and the United Kingdom. Further regulatory clearances in three additional countries are expected shortly, with the remaining countries anticipated in the weeks and months ahead.

Lung cancer is the leading cause of death among all cancer types and the incidence is set to increase to approximately 3 million cases worldwide by 2030.³ NSCLC is the most common type of lung cancer representing ~80-85% of all diagnoses.⁴ The condition is often diagnosed at a late stage, and less than 30% of patients are alive five years after diagnosis.^5,6 There remains a high unmet need for additional treatment options for people living with NSCLC.

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About TACTI-004
TACTI-004 (Two ACTive Immunotherapies) is a randomised, double-blind, controlled Phase III study evaluating eftilagimod alfa (efti), a first-in-class MHC Class II agonist, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) and chemotherapy as first line therapy for patients with advanced or metastatic non-small cell lung cancer with no EGFR, ALK or ROS1 genomic tumour aberrations. The global trial will enrol approximately 756 patients regardless of PD-L1 expression and with non-squamous or squamous tumours at over 150 clinical sites in over 25 countries. Patients will be randomised 1:1 to receive either efti in combination with pembrolizumab and chemotherapy in the treatment arm or pembrolizumab in combination with chemotherapy and placebo in the control arm. The study’s dual primary endpoints are progression-free survival and overall survival.

About Immutep
Immutep is a late-stage biotechnology company developing novel immunotherapies for cancer and autoimmune disease. The Company is a pioneer in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and its diversified product portfolio harnesses LAG-3’s ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com.

1. Patients randomised 1:1 in AIPAC-003 Phase II to receive 30mg or 90mg dosing of eft in combination with paclitaxel to determine the optimal biological dose consistent with the FDA’s Project Optimus initiative.
2. Immutep’s Efti in Combination with KEYTRUDA® Generates Excellent Overall Survival Benefit in Patients with Metastatic Non-Small Cell Lung Cancer,
October 2023, and Immutep’s Efti Shows Excellent Survival Data from INSIGHT-003 Trial in Non-Small Cell Lung Cancer, November 2024
3. International Agency for Research on Cancer – World Health Organization. Rates of trachea, bronchus and lung cancer.
4. Zappa C & Mousa Non-small cell lung cancer: current treatment and future advances, Transl Lung Cancer Res. 2016 Jun; 5(3): 288–300.
5. Polanco D et al. Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study. J Thorac Dis 2021;13:1485–1494.
6. National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) - https://seer.cancer.gov/statfacts/html/lungb.html

Australian Investors/Media:
Catherine Strong, Sodali & Co.
+61 (0)406 759 268; catherine.strong@sodali.com

U.S. Media:
Chris Basta, VP, Investor Relations and Corporate Communications
+1 (631) 318 4000; chris.basta@immutep.com

FAQ

What is the size and scope of Immutep's (IMMP) TACTI-004 Phase III trial?

The trial will enroll approximately 756 patients across 150+ clinical sites globally, evaluating eftilagimod alfa with KEYTRUDA® and chemotherapy for first-line NSCLC treatment.

Which countries have approved Immutep's (IMMP) TACTI-004 Phase III trial?

16 countries have approved the trial, including Australia, Austria, Belgium, Bulgaria, Canada, Germany, Greece, Hungary, India, Ireland, Italy, Latvia, Lithuania, Portugal, Spain, and the UK.

What dosage of efti will be used in Immutep's (IMMP) Phase III NSCLC trial?

The trial will use 30mg subcutaneous efti dosing, based on previous regulatory discussions and demonstrated efficacy in multiple clinical trials.

What is the market potential for Immutep's (IMMP) NSCLC treatment?

NSCLC represents 80-85% of all lung cancer cases, with lung cancer incidence expected to reach 3 million cases worldwide by 2030, indicating significant market potential.