Immutep (ASX:IMM) announced promising new data from its Phase IIb trial TACTI-003, presented at the ESMO Immuno-Oncology Congress 2024. The trial combines the company’s lead drug candidate, eftilagimod alpha (efti), with the drug KEYTRUDA (pembrolizumab) from Merck & Co. The targeted indication is head and neck squamous cell carcinoma (HNSCC).
Cancer cells hide from T lymphocytes
T cells are the “soldiers” of the immune system and there are different types of T cells. For example, “cytotoxic” T cells recognize and destroy abnormal cells, including cancer cells.
PD-1 is a protein receptor found on the surface of T cells, while PD-L1 is a protein found on cancer cells (and some normal cells).
When PD-L1 binds to PD-1, it effectively “switches off” the T cells, preventing it from attacking the abnormal cell. This is a defense mechanism exploited by cancer cells.
PD-1 inhibitors (of which KEYTRUDA is an example) work by blocking PD-1, preventing it from interacting with PD-L1. This keeps the T cells active.
The amount of PD-L1 protein in a tumor is measured by the combined PD-L1 positive score (CPS). A high CPS suggests that the patient would respond well to therapies like KEYTRUDA. But if a tumor has very little PD-L1 (for example, its CPS is less than 1), this suggests that it does not rely on the PD-1/PD-L1 pathway to evade the immune system. Instead, it could use another mechanism. In this scenario, blocking the PD-1 receptor would have little effect.
Immutep’s drug efti is not a PD-1 inhibitor per se, but it stimulates a broader immune response, promoting T cell activation and proliferation. This allows PD-1 inhibitors like KEYTRUDA to become more effective.
The results
Immutep’s results show a marked improvement over historical results for HNSCC patients with a CPS score less than 1 (which represent approximately 20% of all HNSCC patients).
- Overall survival at 12 months. This is the percentage of the patient group who are alive after 12 months. Typically, when treated with PD-1 inhibitors alone, the 12-month overall survival is 39%. In contrast, Immutep reports a 12-month overall survival rate of 67% when efti is combined with KEYTRUDA.
- Progression-free survival. This is the time from the start of treatment until the cancer progresses, gets worse, or the patient dies. It is reported as a “median” (the time at which 50% of the patient group experienced worsening of symptoms). For anti-PD1 treatment alone, this figure is 2.1 months. With efti, 5.8 months.
- Response duration. This is the time between when treatment starts to work and when the cancer gets worse. For anti-PD1 alone, there is a median of 2.6 months. With efti it’s been 9.3 months so far.
- Objective response rate. This is the percentage of patients whose tumors shrink significantly (partial response) or disappear completely (complete response). For anti-PD1 drugs alone, it’s 5.4%. With efti, it’s 35.5%.
- Full answer. That is, the cancer becomes undetectable by CT scan or other clinical measures. With anti-PD1 alone, there is no complete answer. But Immutep reports a complete response of 12.9% or 16.1% (depending on the standard used to measure tumor response to treatment).
Marc Voigt, CEO of Immutep, said the data highlights the potential for EFTI to address a critical unmet need. “Patients with PD-L1 expression below 1 have very limited treatment options, which usually involve chemotherapy. These data highlight the possibility of a new approach for up to 20% of these patients,” he said.
Immutep shares are trading up 2.82% at 36.5 cents.
