Immutep Announces Positive Results from TACTI-003 Phase Iib Trial of Efti

Immutep Announces Positive Results from TACTI-003 Phase Iib Trial of Efti

By, Admin 16 July 2024

Immutep announces positive results from TACTI-003 phase IIb trial of efti in combo with Keytruda to treat HNSCC patients with negative PD-L1 expression

Overview

Immutep Limited (Immutep), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, announces positive results from Cohort B of the TACTI-003 (KEYNOTE-PNC-34) phase IIb trial evaluating eftilagimod alfa (efti) in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy Keytruda (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients (1L HNSCC) with negative PD-L1 expression. The updated efficacy and safety data was presented by Dr. Robert Metcalf during an oral presentation at the ESMO Virtual Plenary session at 18:30-19:30 CEST on 11 July 2024.

The outcome

  • The investigational immuno-oncology (IO) combination utilising efti and Keytruda achieved an objective response rate (ORR) of 35.5% (11 of 31 evaluable patients) and a disease control rate (DCR) of 58.1%, according to RECIST 1.1, in 1L HNSCC patients whose tumours do not express PD-L1 (Combined Positive Score [CPS] <1). 
  • These results are among the highest recorded for a chemotherapy-free approach in negative PD-L1 patients and compare favourably to a historical control of 5.4% ORR and 32.4% DCR from anti-PD-1 monotherapy.

Response for IO combination

Additionally, the IO combination attained a high complete response rate of 9.7% (3 of 31 patients), which compares favourably to a historical control of 0% from anti-PD-1 monotherapy in 1L HNSCC patients with a CPS <1.2 Notably, one patient with early progressive disease according to RECIST 1.1 has evolved into a confirmed partial responder who remains on therapy after 14 months, resulting in a 38.7% ORR for the IO-combination, according to iRECIST.

From The Christie NHS Foundation Trust

  • Robert Metcalf, MD, PhD, The Christie NHS Foundation Trust, Manchester, UK, stated, The high response rate from this novel immunotherapy combination is well above other treatment approaches without chemotherapy. It matches historical response rates from chemotherapy-based treatments but without the associated toxicities. This is really significant for patients with head and neck squamous cell carcinomas who have a CPS less than one and for whom chemotherapy is the current first line treatment.
  • Achieving complete responses in this group bodes well for this immunotherapy combination's future potential, especially given the positive trend in response durability. The clinically meaningful response rate and high unmet medical need warrant further investigation of eftilagimod plus pembrolizumab in this patient population.

Durability of Responses

  • Durability of responses is tracking well as has been seen in other clinical trials when efti is combined with Keytruda. 
  • Over 50% of patients in Cohort B received treatment for at least six months with three additional patients nearing this threshold at the time of data cut off (11 March 2024). 
  • The combination also continues to have a favourable safety profile with no new safety signals observed.
  • This new data adds to the body of evidence that efti’s novel activation of antigen-presenting cells provides a strong boost to the immune system, enhancing the potential of immune checkpoint inhibitors such as Keytruda. 
  • Importantly, as the only MHC Class II agonist in clinical development today, efti is generating a broad anti-cancer immune response in a unique and safe manner across all levels of PD-L1 expression, especially in patients with negative expression (CPS <1).

Based on the encouraging efficacy and high unmet medical need, Immutep will discuss the path forward with regulatory agencies. Efti has received FDA Fast Track designation in 1L HNSCC regardless of PD-L1 expression. The prevalence for CPS <1, CPS 1-19, and CPS >20 PD-L1 expression levels are approximately 20%, 30%, and 50% of the HNSCC patient population, respectively.

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

TACTI-003 Trial

  • The TACTI-003 (KEYNOTE-PNC-34) trial is an ongoing Phase IIb study evaluating eftilagimod alfa (efti), Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy Keytruda (pembrolizumab) as first line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). 
  • The randomized Cohort A portion of the study is evaluating efti in combination with pembrolizumab as compared to pembrolizumab monotherapy in patients with PD-L1 positive (Combined Positive Score [CPS] =1) tumours, whereas Cohort B is evaluating efti in combination with pembrolizumab in patients with PD-L1 negative tumours.
  • The primary endpoint of the study is Overall Response Rate of evaluable patients according to RECIST 1.1. 
  • Secondary endpoints include Overall Survival, Overall Response Rate according to iRECIST, Progression Free Survival, and Duration of Response.

About Efti

  • Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. 
  • As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. 
  • It also upregulates the expression of key biological molecules like IFN-? and CXCL10 that further boost the immune system’s ability to fight cancer.
  • Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. 
  • Its favourable safety profile enables various combinations, including with anti-PD-[L] immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA).

About Immutep

Immutep is a clinical-stage biotechnology company developing novel LAG-3 immunotherapy for cancer and autoimmune disease.

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