Immutep's lead product well tolerated in melanoma trial

Biotechnology company Immutep (ASX: IMM) has announced confirmation from the Database Safety Monitoring Board (DSMB) that the company’s lead product, eftilagimod alpha, has been found safe and well tolerated when combined with pembrolizumab (KEYTRUDA) at doses up to 30 mg per subcutaneous injection.

Eftilagimod alpha (efti or IMP321) is a soluble LAG-3Ig fusion protein based on the LAG-3 immune control mechanism, which plays a vital role in the regulation of the T cell immune response. Eftilagimod alpha alone, or in other drug combinations, has completed early Phase II trials as an APC activator boosting T cell responses for cancer chemo-immunotherapy.

Now, in what is said to be the first-in-man TACTI-mel (Two ACTive Immunotherapies in melanoma) Phase I clinical trial in Australia, efti has been combined with pembrolizumab in unresectable or metastatic melanoma patients. The patients eligible to participate in the trial are those that have either had a suboptimal response or had disease progression with pembrolizumab monotherapy. The combination starts at cycle five of pembrolizumab and is limited to six months of treatment.

The data to date shows no safety concerns from the combination with doses of efti at 1, 6 and 30 mg. No drug-related serious adverse events have been reported and the DSMB concluded repeated injections of efti are safe and well tolerated.

Encouraged by the interim results, Immutep now plans to expand the TACTI-mel study by six patients at 30 mg of efti in combination with pembrolizumab starting at cycle one with treatment duration of 12 months.

“There is limited clinical experience with combining an APC activator such as efti with an immune checkpoint inhibitor such as pembrolizumab, analogous to pushing the accelerator and also releasing the brakes on cancer-fighting T cells,” said Dr Frédéric Triebel, Immutep’s chief scientific and medical officer.

“Therefore, the TACTI-mel trial design included certain key safety measures such as starting with a low dose and at cycle five, which excludes patients with early severe adverse events to pembrolizumab, and limiting treatment to six months.

“The positive results now provide the basis to safely extend the clinical trial to start at cycle one with the recommended Phase II dose and for a 12-month duration, meaning patients could benefit earlier and for longer from the combination.”

The news was announced a little over a week after Immutep received a milestone payment from the company’s Chinese partner for eftilagimod alpha, EOC Pharma. The payment of US$1 million relates to the clinical development of eftilagimod alpha in China and follows the granting of EOC Pharma’s Investigational New Drug (IND) application in China.

“We are very pleased with the recent progress EOC Pharma has made in China,” said Immutep CEO Marc Voigt. “Given the recent regulatory reform, we are optimistic about eftilagimod’s navigation of the Chinese Food and Drug Administration’s regulatory pathway and its clinical development. We look forward to supporting our partner EOC Pharma.”

“We have been encouraged by the CFDA approval of the IND,” added EOC’s CEO, Xiaming Zou. “Eftilagimod alpha showed impressive activity in a European Phase 1 clinical trial as well as in the safety run-in phase of AIPAC in metastatic breast cancer, and we are confident Chinese patients will experience similar clinical benefit. We also look forward to entering a new phase of collaboration with our partner Immutep.”

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