Immutep tries again

Australia’s Immutep is attempting to salvage some pride from the Tacti-003 trial of its Lag3 project eftilagimod alpha in first-line head and neck cancer, revealing updated results from one of this small study’s three cohorts, and claiming that these are “among the highest recorded for a chemotherapy-free approach” in this setting.

The group’s enthusiasm suggests that, having had to raise cash from investors to take efti into a phase 3 lung cancer trial alone and without a partner, it still sees a path forward in head and neck – despite the fact that, overall, Tacti-003 was a bust. Immutep stock today closed up 20%; that’s impressive, but still short of where the shares were trading before Tacti-003 was toplined last month.

That revelation showed that in the study’s controlled cohorts, in high (≥20%) and low (1-19%) PD-L1 expressers, efti plus Keytruda wasn’t meaningfully different in terms of ORR versus Keytruda alone. However, the group asked investors to cling to the hope of an uncontrolled third cohort, in 26 PD-L1 negatives, in whom it cited a 27% ORR.

Now that number has been updated to 36%, across 31 evaluable patients. The result concerns the same 11 March cutoff as the results toplined for the first two cohorts last month, so it appears that Immutep was holding back the data in PD-L1 non-expressers specifically for an ESMO virtual plenary, which took place yesterday.

Cross-trial comparison

Immutep again cited a favourable cross-trial comparison against the 5% ORR that Keytruda monotherapy recorded in a sub-analysis of PD-L1 non-expressers in Keynote-048. It also played up the fact that three of 31 patients given efti plus Keytruda went into complete remission, and that responses were seen in one of four HPV-positive and two of seven HPV-negative patients.

However impressive these data might seem, the obvious caveat is that they come from just one cohort, with no on-trial control, from a small study that overall has yielded some pretty conflicting findings. Moreover, ORR has previously not been especially informative in head and neck cancer.

Additional cross-trial analyses reveal that the 36% ORR for efti plus Keytruda isn’t far off the 31% that Keytruda plus chemo has scored in this setting, and is short of the 42% for Erbitux plus chemo. Of course, Immutep has a valid argument in stressing that efti plus Keytruda is a chemo-free regimen.

The company says up to 20% of head and neck cancer patients have tumours that don’t express PD-L1, and it now plans to discuss with regulators a path forward for efti in this setting.

Cross-trial comparison in 1st-line, PD-L1 negative (<1%) head & neck cancer

Notes: *first disclosed in Apr 2024 press release; **at 11 Mar 2024 cutoff. Source: OncologyPipeline.