Immutep (ASX:IMM) has announced promising new data from its Phase IIb TACTI-003 trial, presented at the ESMO Immuno-Oncology Congress 2024. The trial combines the company’s lead drug candidate eftilagimod alpha (efti) with Merck & Co’s drug KEYTRUDA (pembrolizumab). The targeted indication is head and neck squamous cell carcinoma (HNSCC).
Cancer cells hiding from T-cells
T-cells are the “soldiers” of the immune system, and there are different types of T-cells. For instance, “cytotoxic” T-cells recognise 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 “turns off” the T-cell, preventing it from attacking the abnormal cell. This is a defence mechanism cancer cells exploit.
PD-1 inhibitors (of which KEYTRUDA is an example) work by blocking PD-1, stopping it from interacting with PD-L1. This keeps T-cells active.
The amount of PD-L1 proteins in a tumour is measured by the PD-L1 Combined Positive Score (CPS). A high CPS suggests that the patient would respond well to therapies like KEYTRUDA. But if a tumour has very little PD-L1 (for instance, its CPS is less than 1), this suggests it’s not relying on the PD-1/PD-L1 pathway to evade the immune system. Instead, it might be using some other mechanism. In this scenario, blocking the PD-1 receptor would little effect.
Immutep’s efti drug isn’t a PD-1 inhibitor as such, but it stimulates a broader immune response, promoting the activation and proliferation of T-cells. This allows PD-1 inhibitors like KEYTRUDA to become more effective.
The results
Immutep’s results show a clear improvement over historical outcomes for HNSCC patients with a CPS score less than 1 (who represent about 20% of all patients with HNSCC).
- 12-month overall survival. This is the percentage of the patient group who are alive after 12 months. Typically, when treated with only PD-1 inhibitors, 12-month overall survival is 39%. In contrast, Immutep reports a 67% 12-month overall survival rate when efti is combined with KEYTRUDA.
- Progression-free survival. This is the time from start of treatment until the cancer progresses, worsens, or the patient dies. It’s reported as a “median” (the time at which 50% of the patient group has experienced worsening symptoms). For anti-PD1 therapy alone, this figure is 2.1 months. With efti, 5.8 months.
- Duration of response. This is the time from when the treatment starts working until the cancer gets worse. For anti-PD alone, there’s a 2.6-month median. With efti, it’s 9.3 months so far.
- Objective response rate. This is the percentage of patients whose tumours shrink significantly (partial response) or disappear completely (complete response). For anti-PD alone, it’s 5.4%. With efti, it’s 35.5%.
- Complete response. Ie, the cancer becomes undetectable on scans or other clinical measures. With anti-PD alone, there is no complete response. But Immutep reports 12.9% or 16.1% complete response (depending on which standard is used to measure tumour response to treatment).
Immutep CEO Marc Voigt 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 that typically involve chemotherapy. This data underscores the possibility of a new approach for up to 20% of these patients,” he said.
Shares in Immutep are trading 2.82% higher at 36.5 cents.