Immutep and the Australian biotech’s investors have been caught off guard by the unexpected failure of its LAG-3 candidate in a phase 3 study.
The Sydney-based company had been evaluating the experimental drug, called eftilagimod alfa (efti), in combination with Merck & Co.’s Keytruda as a first-line therapy for patients with advanced or metastatic non-small cell lung cancer with no EGFR, ALK or ROS1 genomic tumor aberrations.
The trial was expected to enroll about 756 patients regardless of PD-L1 expression across more than 25 countries, with the primary endpoints assessing progression-free survival and overall survival.
But Immutep disclosed Friday morning that after reviewing the available safety and efficacy data, the study’s independent data monitoring committee had recommended ending the trial for futility. As a result, the biotech said it would wind down the study.
Efti is a LAG-3 fusion protein designed to activate antigen-presenting cells to boost an immune response. Today’s unexpected clinical miss comes after an efti-Keytruda combo was shown to help patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) live a median of 17.6 months in a cohort of a phase 2b study last year. At the time, the readout was deemed “impressive” by a Jefferies analyst.
That same cohort had demonstrated a 35.5% objective response rate—including 12.9% complete responses—back in 2024.
Immutep CEO Marc Voigt said this morning that the company was “very disappointed and surprised” with the analysis of the phase 3 study “in light of efti’s performance in every other clinical trial.”
“We are currently conducting a comprehensive review of the available data to better understand the results and determine the appropriate next steps for the program,” Voigt added.
Investors also seemed taken aback by the news, sending Immutep’s stock down 80% in premarket trading Friday to 50 cents from a Thursday closing price of $2.76.
The phase 2b data unveiled over the previous two years had involved patients with PD-L1 expression below a combined positive score of 1, and Immutep had been hoping to carve out a niche market in PD-L1-negative disease, which makes up about 20% of first-line HNSCC patients. Voigt had previously pointed out that there are a lack of competitor chemo-free trials targeting this population.
It doesn’t sound like Immutep is ready to give up on this ambition quite yet. In this morning’s release, the company said it “remains focused” on advancing its pipeline—“including efti.”
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The biotech promised to provide an updated outlook on its cash runway—which is now expected to stretch “well beyond” the previous estimate of the second quarter of 2027—and will “reassess capital allocation priorities once operational assessments and a full analysis of the study data have been finalized.”
Analysts at Jefferies agreed the news from the phase 3 study was “very surprising.”
While they acknowledged that Immutep does have another LAG-3 drug in the clinic in the form of the autoimmune-disease-focused IMP761, the analysts said that due to the candidate’s early stage of development, they don’t yet value it.
Immutep’s partner Merck wasn’t the only company that had spied potential in efti. As recently as December, Dr. Reddy’s Laboratories paid $20 million for the rights to the drug in certain non-key markets.