Directors Report (Continued)
The first patient was enrolled and safely dosed with the chemotherapy-free triple combination therapy in July
2023, and currently a total of 9 patients have been safely dosed.
Institute of Clinical Cancer Research (IKF) INSIGHT Clinical Trial Platform
INSIGHT is an ongoing investigator-initiated Phase I clinical trial platform investigating efti in different combination treatments. It consists of five
different arms from strata A to E, with active arms reported on below. The trial is being conducted by the Institute of Clinical Cancer Research (IKF) at Northwest Hospital, Frankfurt, Germany.
INSIGHT-003 (Stratum C) - Phase I triple combination with standard-of-care anti-PD-1 therapy and chemotherapy
INSIGHT-003 evaluates a triple combination therapy consisting of efti and an approved standard of care combination of
chemotherapy (carboplatin and pemetrexed) and anti-PD-1 therapy (pembrolizumab) in 50 patients as first line treatment in
non-squamous NSCLC adenocarcinomas.
During the first half, encouraging efficacy and tolerability data was
presented at the ESMO Congress 2023. A strong 71.4% Overall Response Rate was reported, along with a 90.5% Disease Control Rate and 10.1-month median PFS. Median Overall Survival (OS) has not yet been reached,
despite 81% of patients having low or negative PD-L1 expression.
In the difficult-to-treat PD-L1 TPS <50% patient population, the triple combination achieved a high 70.6% response rate and median PFS above 10 months in both low (TPS 1-49%) and negative (TPS <1%) PD-L1 patients. These low and negative expressing PD-L1 patients collectively represent roughly 70% of
the overall NSCLC patient population and remain an area of high unmet need. The strong ORR compares favourably to reported results from an independent registrational trial of
anti-PD-1 and doublet chemotherapy that yielded a response rate of 40.8% in the same patient population.
The trial was expanded to four sites across Germany in November 2023 to support faster enrolment. Currently, 31 patients are enrolled in the study.
INSIGHT-005 (Stratum E) - New Phase I trial with Merck KGaA, Darmstadt, Germany
INSIGHT-005 is an open-label Phase I trial evaluating the safety and efficacy of efti in combination with BAVENCIO® (avelumab) in up to 30 patients with metastatic urothelial carcinoma. The study is being conducted under a Clinical Trial Collaboration and Supply Agreement between Immutep and Merck KGaA,
Darmstadt, Germany. The study is jointly funded by Merck KGaA, Darmstadt, Germany and Immutep.
Following receipt of regulatory approvals, the first
patient was enrolled and safely dosed in the trial in December 2023.
Manufacturing of Efti
During the half year, Immutep received regulatory authorisation for efti manufactured at commercial 2,000L scale for use in clinical trials across multiple
European countries including Germany, Belgium, Denmark and the United Kingdom. This followed the successful scale up of the manufacturing process of efti (from the 200L process) to commercial scale.
Preclinical Research & Development
IMP761
IMP761 is Immuteps proprietary preclinical
candidate for autoimmune diseases and the worlds first LAG-3 agonist antibody. LAG-3 is a promising target in autoimmune diseases due to its ability to switch off
activated T cells that are damaging tissue or creating inflammatory responses.
IMP761 has been designed to restore balance to the immune system. It does
this by silencing self-antigen-specific memory T cells, which are the underlying cause of many autoimmune diseases. It has the potential to treat the underlying causes of many autoimmune diseases, such as inflammatory bowel disease, rheumatoid
arthritis, and multiple sclerosis, rather than merely treating the symptoms.
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