A New Generation of Cancer & Autoimmune Disease Treatment

Immunotherapy Clinical Trials.


Two ACTive Immunotherapies-003 (TACTI-003) is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). TACTI-003 is a randomised, controlled Phase IIb clinical trial in 1st line Head and Neck Cancer (1L HNSCC), which is evaluating the safety and efficacy of eftilagimod alpha (efti) in combination with MSD’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) as a first line therapy in unresectable recurrent or metastatic HNSCC patients with PD-L1 positive (CPS ≥1) tumours (Cohort A) and PD-L1 negative tumours (Cohort B).  The primary endpoint is Overall Response Rate (ORR) according to RECIST 1.1. Secondary endpoints include OS and Progression Free Survival (PFS).

Efti was granted Fast Track designation by the FDA for the treatment of 1L HNSCC in April 2021, based on the promising data package from Immutep, including data from the Phase II TACTI-002 trial (KEYNOTE-798) in 2nd line HNSCC (see below). In October 2022, the Independent Data Monitoring Committee (IDMC) for the TACTI-003 trial reviewed initial safety data and recommended continuing the trial with no modifications. The IDMC also reviewed initial efficacy data, although this was not the primary focus of the analysis. As reported in November 2023, the trial completed enrollment with 171 patients enrolled at over 30 centers across the United States, Europe, and Australia. A total of 138 patients with recurrent or metastatic HNSCC whose tumors express PD-L1 (CPS>1) have been enrolled into the 1:1 randomized Cohort A and 33 patients with PD-L1 negative tumors have been enrolled in Cohort B. The Company expects to report data from the trial in H1 CY2024.  

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Two ACTive Immunotherapies-002 (TACTI-002) is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). TACTI-002 is an all-comer study in terms of PD-L1 status evaluating the combination of eftilagimod alpha (efti) with MSD’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in patients with first and second line non-small cell lung cancer (1L and 2L NSCLC, Parts A and B) and second line head & neck squamous cell carcinoma (2L HNSCC, Part C). This Phase II, Simon’s two-stage, non-comparative, open-label, single-arm, multicentre clinical study recruited patients at centres across Australia, Europe, and the US, and completed enrolment in November 2021.

Efti has received Fast Track status from the United States Food and Drug Administration (FDA) in 1L HNSCC (April 2021) and in combination with pembrolizumab in 1L NSCLC (October 2022), based largely on the promising clinical data regardless of PD-L1 expression in 2L HNSCC and 1L NSCLC from the Phase II TACTI-002 (KEYNOTE-798) trial. 

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AIPAC-003 (Active Immunotherapy, Eftilagimod Alpha, and PAClitaxel) is an integrated Phase II/III trial to evaluate eftilagimod alpha (“efti”) in combination with paclitaxel for the treatment of metastatic HER2-neg/low breast cancer (MBC) and triple-negative breast cancer, an aggressive cancer with limited treatment options. The Company and the US Food and Drug Administration (FDA) agreed to the trial design, which also incorporates feedback from Scientific Advice meetings with the European Medicines Agency (EMA).

As a first-in-class soluble LAG-3 protein targeting MHC Class II ligands on antigen-presenting cells (APC), efti is uniquely positioned to improve clinical outcomes from standard-of-care chemotherapy. Its activation of APCs (e.g., dendritic cells, monocytes) triggers a broad immune response that includes significant increases in cytotoxic CD8+ T cells armed with chemo-induced tumour antigens to target cancer. This synergy was demonstrated by the AIPAC Phase IIb trial’s encouraging efficacy and safety, including a +2.9-month median overall survival (mOS) improvement, statistically significant mOS improvements between 4.2 to 19.6 months across three pre-specified subgroups, a statistically significant increase in cytotoxic CD8 T cells that correlated with improved OS, a higher 48% ORR (vs 38% for chemo alone), and a superior Quality of Life preservation. Unlike the prior AIPAC trial that administered efti + paclitaxel on different days and stopped chemotherapy at six months, patients will receive same-day administration of efti + paclitaxel that can continue until disease progression in AIPAC-003.

In November 2023, the Company announced the completion of the safety lead-in portion of the AIPAC-003 trial evaluating for the first time 90mg of efti in combination with paclitaxel. The evaluation of 90mg efti dosing in combination with paclitaxel is driven by efti’s excellent safety profile, along with the FDA’s Project Optimus initiative in oncology. The treatment was well tolerated with no dose limiting toxicities, and this good safety profile enabled the lead-in phase to be closed after the first 6 patients.

Following the recommendation of the independent Data Monitoring Committee (IDMC), the Company has proceeded into the randomized (1:1) Phase II portion of study consisting of up to 58 evaluable patients that will receive 30mg efti or 90mg efti to determine the optimal biological dose in combination with paclitaxel. Depending on the Phase II results, potential regulatory actions and resources, a randomized, double-blinded, placebo-controlled Phase III portion will then follow. The Phase III will have overall survival as the primary endpoint and may include a specific patient population. For more information about the trial visit:


INSIGHT-003 is an investigator-initiated trial conducted by the Institute of Clinical Cancer Research IKF at Krankenhaus Nordwest in Frankfurt. It is being run as the third arm (Stratum C) of the ongoing Phase 1 INSIGHT trial with Prof. Dr. Salah-Eddin Al-Batran as lead investigator. INSIGHT-003 is the first trial evaluating Immutep’s lead product candidate, eftilagimod alpha (efti/IMP321), as part of a triple combination therapy with standard-of-care anti-PD-1 therapy and doublet chemotherapy (carboplatin/pemetrexed) in advanced 1st line non-squamous non-small cell lung cancer.

Promising efficacy and tolerability data was presented from the INSIGHT-003 trial at the ESMO Congress 2023 in October. A strong ORR of 71.4% was reported, along with a Disease Control Rate of 90.5% and a 10.1-month median PFS. Median OS has not been reached, despite 81% of patients having low or negative PD-L1 expression. In the difficult-to-treat PD-L1 TPS <50% patient population (i.e. those with low or negative expression), which represents roughly 70% of the overall NSCLC patient population and remains an area of high unmet need, the triple combination achieved a high 70.6% response rate and median PFS that exceeded 10 months in both low (TPS 1-49%) and negative (TPS<1%) PD-L1 patients. In November, the INSIGHT-003 trial was expanded to four sites across Germany and recruitment is expected to be completed in 1H CY2024. For further information about the study and additional information, please visit:


INSIGHT-005 is an investigator-initiated, open-label Phase I study evaluating the safety and efficacy of Immutep’s lead product candidate, efti, in combination with avelumab (BAVENCIO®) in up to 30 patients with metastatic urothelial cancer. This Phase I trial is Immutep’s second collaboration with Merck KGaA, Darmstadt, Germany, which builds on the encouraging clinical data previously reported from INSIGHT-004 in multiple solid tumour indications.

BAVENCIO® is a checkpoint inhibitor owned by Merck KGaA, Darmstadt, Germany, that works by targeting and blocking a protein called PD-L1 on the surface of cancer cells and certain immune cells, activating the cells to find and kill cancer cells. It is approved as a monotherapy for first-line maintenance treatment for adult patients with advanced urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy in more than 60 countries around the world.  Under the Agreement, Immutep and Merck KGaA, Darmstadt, Germany will jointly fund the INSIGHT-005 study. The trial will take place in Germany and will be conducted by the Institute of Clinical Cancer Research, Krankenhaus Nordwest (IKF) and other German cancer centers including Helios Klinikum Bad Saarow. In January 2024, the Company announced the first patient was enrolled and safely dosed in the INSIGHT-005 trial. For more information, please click here.


EFTISARC-NEO is an open-label Phase II trial evaluating eftilagimod alpha (efti) in combination with pembrolizumab and radiotherapy in up to 40 soft tissue sarcoma (STS) patients in the neoadjuvant (prior to surgery) setting. Efti’s targeting and unique activation of antigen-presenting cells (e.g., dendritic cells, monocytes) via MHC Class II molecules leads to broad adaptive and innate immunity to fight cancer, including proliferation of CD8+ cytotoxic T cells that can be armed with radiotherapy-induced tumour antigens. The combination of efti with radiotherapy and the anti-PD-1 therapy KEYTRUDA® (pembrolizumab) has the potential to generate a robust anti-tumour immune response in the immunosuppressed tumour microenvironment (TME) of STS.

This is the first time efti will be tested in the neoadjuvant setting, which importantly will provide access to tumour tissue prior to and after treatment, where the impact of this novel triple combination on the TME can be assessed. The investigator-initiated study will be primarily funded by the Maria Skłodowska-Curie National Research Institute of Oncology with an approved grant from the Polish government awarded by the Polish Medical Research Agency program. Immutep will provide efti at no cost as well as technical support. For more information, please click here.


INSIGHT-004 is the 4th arm (Stratum D) of the INSIGHT Phase I clinical trial. It was conducted under lmmutep's clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer Inc., and evaluated the combination of eftilagimod alpha (efti) with avelumab, a human anti-PD-L1 antibody, in 12 patients with advanced solid malignancies. The Institute of Clinical Cancer Research, Krankenhaus Nordwest GmbH in Frankfurt, Germany (IKF) was the sponsor of the clinical trial and it was conducted under the existing protocol of IKF's ongoing INSIGHT Phase I study.

Immutep reported final data from INSIGHT-004 at the American Society of Clinical Oncology’s (ASCO) Annual Meeting in June 2021. Promising activity signals were demonstrated with a response rate of 41.7% in patients and disease control rate (DCR) of 50% according to RECIST 1.1. In addition, deep and durable responses were seen in patients with low or no PD-L1 expression and in indications such as gastroesophageal and cervical cancer, that typically do not respond to immune checkpoint therapy. The combination therapy also showed a good safety profile.  

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Two ACTive Immunotherapies in melanoma (TACTI-mel) was a Phase I safety and dose finding clinical trial of efti in combination with pembrolizumab (KEYTRUDA®) in patients with locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma. Patients having a suboptimal response or disease progression with pembrolizumab monotherapy were eligible for the study and received the combination of pembrolizumab plus efti. TACTI-mel took place in Australia and involved four cohorts of six patients.

  • Part A included the first three cohorts testing different dosages of efti (1mg, 6mg and 30mg) in combination with pembrolizumab, with efti treatment given for six months only and commencing at cycle five of pembrolizumab treatment.
  • Part B included the remaining cohort of six patients testing a 30mg dosage of efti given for 12 months in combination with pembrolizumab, starting at cycle 1, day 1 of pembrolizumab treatment.

Final efficacy data from TACTI-mel showed that patients responded well with deep & durable responses and an encouraging Overall Response Rate of 33% in Part A and 50% in Part B. In addition, the study reported the complete disappearance of all target tumour lesions for a number of patients and one complete confirmed response where the tumour had completely disappeared. Efti also had a favorable safety profile. 

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