Immunotherapy Clinical Trials.

TACTI-004 Phase III Trial

Two ACTive Immunotherapies-004 (TACTI-004) is being conducted in collaboration with MSD (Merck & Co., Inc., Kenilworth, NJ, USA). TACTI-004 is a 1:1 randomised, double-blind, multinational, controlled Phase III clinical trial in 1st line Non-Small Cell Lung Cancer (1L NSCLC). The trial is designed to evaluate eftilagimod alfa (efti) in combination with MSD’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) and standard chemotherapy compared to the standard-of-care combination of KEYTRUDA and chemotherapy and placebo in metastatic 1L NSCLC, regardless of PD-L1 expression. The dual primary endpoints are progression-free survival (PFS) and overall survival (OS) and this pivotal PD-L1 all comer trial includes a pre-specified futility boundary and pre-planned interim analysis. The globally conducted study will enrol approximately 750 NSCLC patients (including both squamous and non-squamous subtypes).

For more information about the study, please visit:

• clinicaltrials.gov (NCT06726265)

TACTI-003

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. 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.  

For more information about the study, please visit:

• clinicaltrials.gov (NCT04811027)

TACTI-002

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. 

For more information about the study, please visit:

• clinicaltrials.gov (NCT03625323)

AIPAC-003

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. 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 study, please visit:

• clinicaltrials.gov (NCT05747794)

INSIGHT-003

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.

For further information about the study, please visit:

• clinicaltrials.gov (NCT03252938)

INSIGHT-005

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. INSIGHT-005 will be conducted by the Institute of Clinical Cancer Research IKF at Krankenhaus Nordwest in Frankfurt as part of the investigator-initiated INSIGHT platform for studies investigating efti in different combination treatments and routes of administration. INSIGHT currently consists of 5 different arms from stratums A to E (INSIGHT-005 is Stratum E).

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.

For more information about the study, please visit:

• clinical trials.gov (NCT03252938)

INSIGHT-004

INSIGHT-004 was the 4th arm (Stratum D) of the INSIGHT Phase I clinical trial. The study 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.