ImmuFact (eftilagimod alpha) / Immutep, EOC Pharma - LARVOL DELTA

A phase III placebo-controlled study of eftilagimod alfa plus pembrolizumab and chemotherapy in metastatic non-small cell lung cancer. (PubMed, Future Oncol) - P3 | "TACTI-004 will evaluate whether efti can mitigate resistance to ICIs when added to SoC in NSCLC, irrespective of PD-L1 tumor status. www.clinicaltrials.gov identifier is NCT06726265."

IO biomarker • Journal • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • ROS1

KEYNOTE-C34: Combination Study With Eftilagimod Alpha (a Soluble LAG-3 Fusion Protein) and Pembrolizumab in Patients With Recurrent or Metastatic HNSCC (clinicaltrials.gov) - P2 | N=171 | Completed | Sponsor: Immutep S.A.S. | Active, not recruiting ➔ Completed

Trial completion • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CTLA4

ImmuFact: “Both efti dose levels (30 and 90 mg) on top of weekly paclitaxel led to strong ORR and strong biological responses in heavily-pretreated MBC patients with no clinically-meaningful or significant differences between the doses as per the pre-defined algorithm”; Breast cancer (Immutep) - SABCS 2025

P2/3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Triple Negative Breast Cancer

Dr Reddy’s Laboratories has inked an exclusive licensing agreement with Australian biotech Immutep, for its investigational immunotherapy Eftilagimod Alfa commercial rights in all countries outside North America, Europe, Japan, and Greater China. (The Economic Times) - "Under the licensing agreement estimated over $370 million (around Rs 3,200 crore) Immutep will receive an upfront payment of $20 million and is also eligible to receive potential development and milestone payments of up to $349.5 million along with 'double-digit' royalties on commercial sales in these markets....Immutep will retain the global manufacturing rights and will supply the product to Dr Reddy’s in the licensed markets."

Licensing / partnership • Non Small Cell Lung Cancer

Optimal biological dose of eftilagimod alpha, a soluble LAG-3 protein, in metastatic breast cancer patients receiving weekly paclitaxel in AIPAC-003 (SABCS 2025) - P2/3 | "These data show that 90 mg efti is less tolerable and does not enhance efficacy. Therefore, the 30 mg SC dose of the APC activator, efti, previously administered in >500 pts with advanced or metastatic cancer in prior phase 1 and 2 studies, is considered the OBD, suitable for evaluation in larger pt populations."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • LAG3

Immutep to Present New Data from AIPAC-003 Phase II at the 2025 San Antonio Breast Cancer Symposium (Immutep Limited Press Release) - "The Phase II study randomised female participants (N=66) with HR+ and HER2-negative/HER2-low metastatic breast cancer (MBC) resistant to endocrine-based therapy (ET) including cyclin-dependent kinase 4/6 (CDK4/6) inhibitors or...mTNBC not eligible for PD-(L)1-based therapy....Both efti dosing levels on top of weekly paclitaxel in heavily pretreated metastatic breast cancer patients, who received a median of three prior lines of systemic therapy, led to strong objective response rates (ORR) and disease control rates (DCR) of 41.9% and 87.1% (30 mg efti) and 48.5% and 78.8% (90 mg efti), respectively, in the evaluable population (N=64). Time to onset of response (TTR) was comparable at 2.0 months (30 mg) versus 1.9 months (90 mg)....AIPAC-003 has resulted in successful completion of FDA’s Project Optimus requirements and selection of 30 mg as efti’s optimal biological dose."

P2 data • HER2 Negative Breast Cancer • Triple Negative Breast Cancer

PRIMARY ENDPOINT AND TRANSLATIONAL CORRELATES FROM EFTISARC-NEO: PHASE II TRIAL OF NEOADJUVANT EFTILAGIMOD ALPHA (EFTI), PEMBROLIZUMAB AND RADIOTHERAPY IN PATIENTS WITH RESECTABLE SOFT TISSUE SARCOMA (CTOS 2025) - No abstract available

Clinical • P2 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Translational Data and Significant Pathologic Response Rates from EFTISARC-NEO Phase II Highlighted in Oral Presentation at CTOS 2025 (GlobeNewswire) - "In the evaluable patient population (N=38), the novel combination with efti reached a median 51.5% tumour hyalinization/fibrosis (p<0.001), meeting the study’s primary endpoint. These promising results were achieved in patients with ten different STS subtypes including rare and/or highly aggressive tumours with poor prognosis such as myxofibrosarcoma (N=16), undifferentiated pleomorphic sarcoma (N=10) and malignant peripheral nerve sheath tumor (N=2)....Disease-free survival and overall survival data are immature at this stage and will be presented in the future."

P2 data • Myxofibrosarcoma • Soft Tissue Sarcoma • Undifferentiated Pleomorphic Sarcoma

Immutep Receives A$4.6 million R&D Tax Incentive from French Government (Immutep Limited Press Release) - "Immutep qualifies for the CIR tax incentive through its subsidiary Immutep S.A.S. due to the research and development conducted in its laboratory in France. The cash payment is provided in respect of expenditure incurred on eligible R&D activities conducted in the European Union in the 2024 calendar year....The funds will be used to support the ongoing and planned global clinical development of eftilagimod alfa and IMP761."

Commercial • Immunology • Oncology

TACTI-004, a double-blinded, randomised phase III trial of eftilagimod alfa plus pembrolizumab (P) + chemotherapy (C) vs placebo + P + C in 1st line advanced/metastatic NSCLC (ESMO 2025) - P1, P2, P3 | "Chemotherapy choice will be histology-dependent: non-squamous NSCLC pts will receive IV cisplatin (75 mg/m 2 ) or carboplatin (AUC 5 or 6) + pemetrexed (500 mg/m 2 ) q3w for 3 mo, then maintenance pemetrexed q3w. Squamous NSCLC pts will receive carboplatin (AUC 5 or 6) + paclitaxel (175 or 200 mg/m 2 ) q3w for 3 mo...Legal entity responsible for the study Immutep S.A.S. Funding Immutep S.A."

Clinical • IO biomarker • Metastases • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CD4 • CD8 • EGFR • PD-L1 • ROS1

EFTISARC-NEO: A phase II study of neoadjuvant eftilagimod alpha, pembrolizumab and radiotherapy in patients with resectable soft tissue sarcoma (ESMO 2025) - P2 | "The most common TRAEs of any grade were wound infection (38%), pain in efti injection site (35%), radiation dermatitis (35%) and hypothyroidism (18%). Conclusions The trial has met its primary endpoint, indicating that this novel combination of efti and pembrolizumab could be further tested in late-stage trials in the neoadjuvant setting in patients with resectable STS treated with radiotherapy."

Clinical • P2 data • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • LAG3

Eftilagimod alpha (soluble LAG-3 protein) combined with first-line chemo-immunotherapy in metastatic non-squamous non-small cell lung cancer (NSCLC): Updates from INSIGHT-003 (IKF614) (ESMO 2025) - P1 | "Methods Pts with advanced or metastatic non-squamous (NSQ) NSCLC receive first-line SOC chemo-immunotherapy with platin + pembrolizumab + pemetrexed combined with s.c. efti (30 mg; q2w for 24 weeks; thereafter q3w up to 52 weeks). Conclusions 30 mg efti on top of SOC is feasible and safe with no new safety signals. The addition of an APC activator to SOC in first-line NSCLC shows very encouraging ORR especially in pts with TPS <50% where the medical unmet need is high."

Clinical • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • LAG3

Immutep Limited…announces the initiation of an investigator-initiated Phase II trial evaluating neoadjuvant eftilagimod alfa (efti) administered subcutaneously as monotherapy and then in combination with standard-of-care chemotherapy prior to surgery in patients with early-stage HR+/HER2-negative breast cancer (GlobeNewswire) - "The study will treat up to 50 evaluable patients in a two-stage design and will be primarily funded by grants and The George Washington (GW) University Cancer Center."

Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

AIPAC-003 - Phase II/III Trial in Metastatic Breast Cancer (The Manila Times) - "Patient follow up, data cleaning and analysis is ongoing, and an update will be provided at the San Antonio Breast Cancer Symposium in San Antonio, Texas, USA in December 2025."

P2/3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

ImmuFact: "The trial has met the primary endpoint, confirming the efficacy and safety of combining eftilagimod alpha and pembrolizumab with radiotherapy"; Soft tissue sarcoma (Immutep) - ESMO 2025

P2 data • Oncology • Soft Tissue Sarcoma

Two Posters at ESMO Congress 2025 Highlight Immutep’s Focus on Changing Treatment Landscape in First Line Non-Small Cell Lung Cancer (Immutep Limited Press Release) - "Notably, the ORR and DCR reported in INSIGHT-003 outperforms historical controls irrespective of PD-L1 levels. This is particularly important for patients with low and no PD-L1 (TPS <50%), who represent over two-thirds of the 1L NSCLC patient population and for whom PD-(L)1 inhibitors typically perform suboptimally. In patients with TPS <50% (N=47), the combination with efti has achieved a strong and improved 61.7% ORR (with an additional partial response since 06 May 2025 data cutoff) as compared to historical control of 40.8%...Additionally, a Trial in Progress ePoster for the TACTI-004 Phase III was presented at ESMO Congress 2025....This global study will enrol approximately 756 patients with advanced/metastatic 1L NSCLC regardless of PD-L1 expression (Tumour Proportion Score or TPS of 0-100%) with non-squamous or squamous tumours at over 150 clinical sites in over 25 countries."

P1 data • Trial status • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer

Primary Endpoint Met in EFTISARC-NEO Phase II Evaluating Neoadjuvant Efti in Soft Tissue Sarcoma and Data Presented at ESMO Congress 2025 (Immutep Limited Press Release) - "The investigator-initiated Phase II study evaluating eftilagimod alfa (efti) with radiotherapy plus KEYTRUDA (pembrolizumab) in the neoadjuvant setting for resectable soft tissue sarcoma (STS) met the primary endpoint and significantly exceeded the study’s prespecified 35% tumour hyalinization/fibrosis. In the evaluable patient population (N=38), the novel combination with efti reached a median 51.5% tumour hyalinization/fibrosis (p<0.001)...These promising results were achieved across multiple STS subtypes and the study proved a very good safety profile for the therapy, with only one grade ≥3 toxicity related to immunotherapy."

P2 data • Soft Tissue Sarcoma

ImmuFact: "Eftilagimod alpha combined with SOC (carboplatin/pemetrexed/ pembrolizumab) in NSQ 1 st line NSCLC led to encouraging ORR (unconf. 62.7% & conf. 58.8%) overall"; Non small cell lung cancer (Immutep) - ESMO 2025

P1 data

Immutep Announces Successful Completion of FDA Project Optimus Requirements (GlobeNewswire) - "The agreement with the FDA on efti’s optimal biological dosing carries strategic importance in the ongoing and future clinical development of this first-in-class immunotherapy, including the global TACTI-004 (KEYNOTE-F91) Phase III trial evaluating efti in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab), and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (1L NSCLC), regardless of PD-L1 expression. With the conclusion of Project Optimus, this registrational study is now in process of opening sites in the United States."

FDA event • Trial status • Non Small Cell Lung Cancer

Immutep Announces Update for TACTI-004 (KEYNOTE-F91) Phase III Trial in First Line Non-Small Cell Lung Cancer (Immutep Limited Press Release) - "Global Phase III trial has enrolled and randomised over 170 patients, reaching an important milestone as this is above the amount needed to conduct the futility analysis. Over 100 clinical sites across 24 countries now activated and open for recruitment....The trial remains on track for the IDMC to conduct the futility analysis in the first quarter of CY2026."

P3 data • Trial status • Non Small Cell Lung Cancer

TACTI-004, a Phase 3 Trial of Eftilagimod Alfa Plus Pembrolizumab (P) + Chemotherapy (C) vs Placebo + P + C in 1St Line NSCLC (IASLC-WCLC 2025) - P1, P2 | "Chemotherapy choice will be histology-dependent: non-squamous NSCLC pts will receive IV cisplatin (75 mg/m2) or carboplatin (AUC 5 or 6) + pemetrexed (500 mg/m2) q3w for 3 mo, then maintenance pemetrexed q3w. Squamous NSCLC pts will receive carboplatin (AUC 5 or 6) + paclitaxel (175 or 200 mg/m2) q3w for 3 mo.Imaging will be performed q6w until week 18, q9w until week 54 & q12w thereafter...Pts may not have tumours with EGFR mutations nor ALK or ROS1 translocations. Stable brain metastasis is acceptable."

Clinical • IO biomarker • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • CD4 • CD8 • EGFR • PD-L1 • ROS1

Immutep Announces Data from EFTISARC-NEO Phase II Evaluating Neoadjuvant Efti in Soft Tissue Sarcoma Accepted for Oral Presentation at CTOS 2025 (Immutep Limited Press Release) - "Data to be presented in the Immunotherapy & Cell Therapy in Sarcoma: Emerging Frontiers session..."

P2 data • Soft Tissue Sarcoma

Immutep Receives Positive Feedback from FDA on Late-Stage Clinical Development of Eftilagimod Alfa in Head and Neck Cancer with CPS <1 (Immutep Limited Press Release) - "Immutep Limited...announces it has received positive and constructive feedback from the...FDA, regarding future clinical development of its first-in-class MHC Class II agonist, eftilagimod alfa ('efti'), for...1L HNSCC patients who have PD-L1 expression below 1 (Combined Positive Score [CPS] <1). Based on its review of the encouraging data in 1L HNSCC with CPS <1 from the TACTI-003 (KEYNOTE-C34) Phase IIb trial...the FDA agreed on the potential of efti in combination with KEYTRUDA to address the high unmet need in this CPS <1 patient segment and is supportive of the combination’s further development. Paths for future clinical development and potential accelerated approval in light of the FDA’s Project FrontRunner include a randomised registrational trial evaluating efti in combination with KEYTRUDA against standard-of-care therapy or alternatively a smaller single-arm study (e.g. 70 - 90 patients)..."

FDA event • Squamous Cell Carcinoma of Head and Neck

Immutep Quarterly Activities Report Q4 FY25 (GlobeNewswire) - "INSIGHT-003 – Phase I Trial in Non-Squamous 1L NSCLC...Data from this trial are expected to be presented at a medical conference later in CY2025...EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma...The trial’s investigators at the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw, the national reference centre for STS in Poland, plan to present results from the study at a medical meeting later in CY2025...AIPAC-003 – Phase II/III Trial in Metastatic Breast Cancer...Patient follow up, data cleaning and analysis is ongoing and an update is anticipated later in CY2025...Immutep is progressing with the ongoing Phase I trial of its autoimmune candidate IMP761....Additional data from the Phase I is expected to follow later in CY 2025."

Clinical data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Non-Squamous Non-Small Cell Cancer • Soft Tissue Sarcoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Efti in Patients With Hormone Receptor Positive/HER2-neg Breast Cancer (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: George Washington University

New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor