Mid-stage promise turns to pivotal bust for Immutep

Based on the mid-stage data Immutep had generated the company made the right decision in taking its soluble Lag3 protein eftilagimod alpha into pivotal development in lung rather than in head and neck cancer. But this move backfired all the same, with the phase 3 Tacti-004 NSCLC trial being terminated for futility on Friday on the advice of its data-monitoring board.

Tacti-004, also known as Keynote-PNC-91, began in mid-2024 after Immutep secured a $60m equity raise, and it compared efti plus Keytruda against chemo in front-line NSCLC irrespective of PD-L1 expression or histology, measuring OS and PFS as co-primary endpoints. Its termination caused Immutep shares to crash 89% on the Australian stock exchange on Friday.

However, the company had ample grounds for pursuing this indication: the uncontrolled phase 2 Tacti-002 study showed promise for the combo on a cross-trial basis against Merck & Co’s Keynote-042 trial. As such, Immuntep hasn’t been the first, nor will it be the last, company to learn that data in a single-arm study in a small number of patients are rarely replicated in the multicentre, controlled setting of a pivotal trial.

For now nothing has been disclosed about what Tacti-004 showed, but presumably Immutep will present the results at a future scientific congress. It was only last month that Tacti-004 reached half of its planned 756-patient recruitment target, suggesting that whatever reasons the DSMB saw to recommend termination were profound, and evident early on.

Efti work continues

Notably, however, the company hasn’t discontinued efti, and says it remains focused on advancing its pipeline, “including efti”.

Still, the head and neck cancer setting where it previously mooted a phase 3 study in PD-L1-low expressers has considerably less backing than NSCLC did. A phase 2 trial, Tacti-003, was a clear failure, and it was only a post hoc analysis of its confusing results that led Immutep to conclude that there was some promise in PD-L1-negative patients. Caveat emptor.

Another possibility is first-line HER2-negative, HER2-low and triple-negative breast cancer, where a phase 2/3 study called Aipac-003 is ongoing. This yielded results from its uncontrolled phase 2 part at last year’s San Antonio Breast Cancer Symposium, but these largely served to confirm 30mg as the go-forward efti dose, and it’s unclear when the phase 3 portion might start.

Immutep ended the 2025 calendar year with $70m in cash, and subsequently banked a $21m up-front fee from Dr Reddy’s in a regional licensing deal covering efti. It says the cash will last “well beyond” the second quarter of calendar 2027, but apart from efti its clinical pipeline comprises autoimmune diseases.

Selected indications for Immutep’s eftilagimod alfa

Source: OncologyPipeline.