Immutep’s efti combination therapies show strong efficacy in soft tissue sarcoma and lung cancer trials

Immutep (ASX: IMM) has presented new data from a Phase II investigator-initiated trial of eftilagimod alpha (efti) in combination with radiotherapy plus Keytruda (pembrolizumab) for patients with soft tissue sarcoma (STS).

Based on preliminary analysis of 21 patients available for primary endpoint assessment, the trial at Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Poland showed that the triple-combination therapy demonstrated significant efficacy in the neoadjuvant setting for resectable STS.

The combination was reported to be safe, with no serious toxicities related to efti or pembrolizumab.

Threefold increase

The combination achieved more than a threefold increase in tumour hyalinisation/fibrosis (with a median of 50%) at the time of surgical resection, compared to a historical median of 15% from standard radiotherapy alone.

In addition to being the primary endpoint of the study, the tumour hyalinisation/fibrosis rate was identified as an important predictor of overall survival for STS patients.

The trial also showed that 71.4% of patients achieved a pathologic response, defined as greater than or equal to 35% hyalinisation/fibrosis, while 9.5% of patients achieved a complete pathologic response.

Difficult-to-treat cancer

“We are pleased with the strength of these preliminary results in this difficult-to-treat cancer,” Immutep chief scientific officer Dr Frédéric Triebel said.

“To see 71.4% of soft tissue sarcoma patients achieving a positive pathologic response is very promising, especially as strong efficacy has been observed across different STS subtypes.”

“We look forward to further evaluating efti’s potential as a neoadjuvant immunotherapy to help drive improved clinical outcomes.”

‘Synergistic effects’

MSCNRIO medical oncologist Katarzyna Kozak said efti was well placed to complement radiotherapy and pembrolizumab in driving better outcomes for STS patients.

“These very encouraging results build our confidence in the synergistic effects of this new therapeutic approach and its potential to treat these patients in dire need of more effective therapies,” she said.

“In particular, the high level of hyalinisation/fibrosis achieved with this novel combination therapy — which is three times above historical results from standard radiotherapy — demonstrates remarkable efficacy in patients with resectable soft tissue sarcomas.”

Immutep’s efti trial is being primarily funded by an approved grant from the Polish government, awarded through the Polish Medical Research Agency program.

Lung cancer trial

Immutep has also announced positive data from an Insight-003 Phase I trial evaluating efti in combination with Keytruda (pembrolizumab) and chemotherapy for the first-line treatment of metastatic non-squamous non-small cell lung cancer (1L NSCLC).

The multi-centre trial, led by the Frankfurt Institute of Clinical Cancer Research (IKF), involves efti administered subcutaneously in conjunction with the approved standard-of-care combination of anti-PD-1 therapy (pembrolizumab) and doublet chemotherapy (carboplatin and pemetrexed) delivered intravenously.

Data from a mature cohort of patients with a minimum follow-up of 22 months have shown results reported to be well above historical controls and expectations.

Patient evaluations to date demonstrate a significant improvement in overall response rate compared to historical controls and safety continues to be favourable with no new incidents.