Immunotherapy Clinical Trials.

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). The study is currently accruing patients at over 25 centers in the United States, Australia, and Europe.

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 January 2023, the trial has enrolled and randomised over 50% of the planned 154 patients and is expected to be fully recruited by mid-2023. 

For more information about the study and additional information, please visit:

• https://clinicaltrials.gov/ct2/show/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 further information about the study and additional information, please visit:

• https://clinicaltrials.gov/ct2/show/NCT03625323
• Part A - Combining the antigen-presenting cell activator eftilagimod alpha (soluble LAG-3) and pembrolizumab: efficacy results from the 1st line non-small cell lung cancer cohort of TACTI-002 (Phase II) - SITC November 2022 Late-breaking Abstract Oral Presentation
• Part B - Final data from a phase II study (TACTI-002) of eftilagimod alpha (soluble LAG-3) & pembrolizumab in 2nd line metastatic NSCLC patients resistant to PD-1/PD-L1 inhibitors - ELCC March 2023
• Part C - Results from a Phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with PD-L1 unselected metastatic 2nd line head and neck squamousFinal results from TACTI-002 Part C: A Phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with metastatic 2nd line head and neck squamous cell carcinoma unselected for PD-L1 - ASCO June 2023

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. 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.

The trial has an open-label lead-in component of 6 to 12 patients to test 90mg efti dosing in combination with paclitaxel driven by efti’s excellent safety profile, along with the FDA’s Project Optimus initiative in oncology. This will be followed by a randomized (1:1) portion of the Phase II consisting of up to 58 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:

• clinicaltrials.gov (NCT05747794)
• AIPAC-003: A randomized, double-blind, placebo-controlled phase 3 trial testing eftilagimod alpha (soluble LAG-3) in HER2-neg/low metastatic breast cancer patients receiving paclitaxel, following an open-label dose optimization - ASCO June 2023

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-small cell lung cancer.

Encouraging initial clinical results from INSIGHT-003 were published during November 2022 in a poster presentation at the Society for Immunotherapy of Cancer (SITC) Annual Meeting (see link below). Subsequent to the results at SITC 2022, the INSIGHT-003 trial was expanded from 20 to 50 patients in March 2023. In May 2023, Immutep announced promising new clinical data from INSIGHT-003 showing the triple combination therapy achieved a 67% overall response rate (ORR) and 91% disease control rate (DCR) in metastatic 1st line non-small cell lung cancer patients (N=21) despite 81% of patients having low or negative PD-L1 expression. The triple combination’s 67% ORR regardless of PD-L1 expression and 65% ORR in patients with PD-L1 TPS <50% (N=17) compare favourably to reported results from a registrational trial of anti-PD-1 and doublet chemo that yielded a 48% ORR regardless of PD-L1 expression and 40.8% ORR in patients with PD-L1 TPS <50%.  For further information about the study and additional information, please visit:

• https://clinicaltrials.gov/ct2/show/NCT03252938
• Feasibility of eftilagimod alpha (soluble LAG-3 protein) combined with standard-of-care therapy in advanced non-small-cell lung cancer (NSCLC) adenocarcinomas. Initial results from INSIGHT 003 - SITC 2022
• Immutep Announces Promising New Clinical Data from Triple Combination Therapy in INSIGHT-003 Trial - 24 May 2023

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, and Pfizer Inc., 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). For more information, please click here.

INSIGHT-004

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.  

For further information about the study and additional information, please visit:

• https://clinicaltrials.gov/ct2/show/NCT03252938
• Phase I INSIGHT platform trial: Advanced safety and efficacy data from stratum D evaluating feasibility and safety of eftilagimod alpha (soluble LAG-3 protein) combined with avelumab in advanced stage solid tumors. - ASCO 2021