PERTH, Australia – Sydney-based Immutep Ltd. reported positive interim data for its phase II basket trial in non-small-cell lung cancer (NSCLC) and head and neck squamous cell carcinoma for its lead immunotherapy in combination with Merck & Co. Inc.’s anti-PD-1 therapy, Keytruda (pembrolizumab).

TACTI-002 (Two ACTive Immunotherapies) is being conducted in collaboration with Merck (known as MSD outside the U.S. and Canada) and is evaluating the combination of Immutep’s eftilagimod alpha (efti) with Keytruda in 109 patients with second-line head and neck squamous cell carcinoma or NSCLC in first- and second-line treatment. The trial is a phase II, two-stage, non-comparative, open-label, single-arm, multicenter trial across the U.S., Europe and Australia.

The study saw encouraging overall response rates (ORR), with 47% of first-line NSCLC patients responding, said Immutep CEO Marc Voigt during a Feb. 26 conference call.

Marc Voigt, CEO, Immutep

Ten patients (59%) in the first-line NSCLC setting are still undergoing treatment and were progression-free at seven months, so Immutep was not able to determine progression-free survival (PFS) yet, Voigt said.

“These results are remarkable given that usually only 20% of patients respond to pembrolizumab monotherapy, if not preselected for high PD-L1 expression,” said the firm’s chief scientific and chief medical officer, Frederic Triebel.

Patient responses are being seen in all three PD-L1 expression level groups, which means the combination treatment “seems to work even in patients not expected to respond to pembrolizumab monotherapy,” Triebel said.

In addition, 33% of second-line head and neck squamous cell carcinoma patients responded, which “compares well to an expected pembrolizumab monotherapy response rate of 15% to 18%, especially taking into account that three patients could not yet be assessed.”

Efti is a soluble LAG-3 (lymphocyte activation gene-3) protein, and the activation of antigen-presenting cells (APC) and subsequent T-cell recruitment with efti may lead to stronger antitumor responses than Keytruda alone.

Frederic Triebel, CSO/CMO, Immutep

The LAG3 protein controls the signaling between specific immune cells: T cells and APCs that are responsible for the adaptive immune reaction. Immutep is applying the LAG-3 protein in three areas – chemo-immunotherapy, immuno-immunotherapy and as an adjuvant to cancer vaccines.

“LAG-3 is an area of growing industry interest as it is considered to be the next major immune checkpoint molecule,” Voigt said. “LAG-3 is seen to be following in the footsteps of other checkpoint molecules such as CTLA4 and PD-1.”

Analysts concurred with that observation, saying that Immutep’s latest update from the TACTI-002 study “delivered a significant amount of contextual data which we feel now frames efti + pembro as a truly competitive I-O therapy, particularly in front-line NSCLC where data is currently most mature,” said Jonestrading Equity Research analysts in a Feb. 18 research note.

“In addition to a reported 47.1% ORR in front-line NSCLC (up from 41.2% as presented at SITC last November), updated safety results and patient PD-L1 expression status breakdown now provide a cohesive picture of the combination’s profile – one we believe is compelling relative to competitive benchmarks and which presents Immutep with notable optionality,” the analysts said.

“Results from the first 19 head and neck cancer patients treated in Stage 1 of Part C are a bit more preliminary (three patients are not yet evaluable), but appear to provide some additional support for the broad utility of the efti + pembro combo, with a 33.3% ORR reported thus far. We maintain our buy rating and 12-month price target of $7/ADS.”

The trial is being run in two parts, and all three indications met the primary ORR with 48 patients enrolled. Some patients have progressed to the second part of the trial.

The company reported that no new safety signals were observed, and only two patients stopped treatment.

In June 2018, Immutep unveiled new data for its phase I immunotherapy study that showed a long lasting and durable response and an ORR of 61% in a melanoma study combining efti with Keytruda. That ORR was seen when tumor size was measured starting from cycle one day one of Keytruda monotherapy and following combination therapy (that starts at cycle five). Two complete responses occurred after 11 and 18 months, and the company concluded that the combination therapy takes time to act. In addition, 66% of patients remained progression-free after six months.

The TACTI-mel phase I trial evaluated the combination of efti in combination with Keytruda in unresectable or metastatic melanoma patients who had disease progression with Keytruda monotherapy.

Efti could change standard of care for metastatic breast cancer

The most advanced efti trial is an ongoing phase IIb Active Immunotherapy PAClitaxel in HER2-/HR+ metastatic (AIPAC) trial testing efti in combination with paclitaxel in metastatic breast cancer in China. Eddingpharm Inc., of Hong Kong, has China rights, and Immutep retains global rights excluding China.

The trial is fully recruited with 227 patients, and PFS data are expected by the end of March 2020.

Voigt said the trial could potentially be a pivotal trial and could serve for regulatory approval. He said it was a “landmark study that could mark the emergence of a new class of immuno-oncology products targeting antigen-presenting cell activators, and efti could be the first new class to show positive results of these I-O products after immune checkpoint inhibitors.”

“Despite advances in earlier treatment options, there has been no improvement for patients receiving chemotherapy for the first time,” Voigt said. “Taxane is widely used, and there are no other therapies approved for this patient population.

“We would expect to improve the standard of care in breast cancer; however, we’re not limited to taxane or hormone receptor-negative breast cancer. We could also expand to triple-negative breast cancer or take on other combinations,” he said.

Immutep shares, trading on Australia’s Securities Exchange (ASX:IMM), dipped 5.81% on the news and were trading at AU40 cents (US26 cents) per share by close of trading Feb. 26.

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