Eftilagimod Alpha/Pembrolizumab Combo Elicits Encouraging Survival Benefits in Anti–PD-1/PD-L1 Refractory NSCLC

Eftilagimod alpha (Efti; IMP321) plus pembrolizumab (Keytruda) demonstrated promising benefits in overall survival (OS) and progression-free survival (PFS) as a second-line treatment in patients with non–small cell lung cancer (NSCLC) who progressed on anti–PD-1/anti–PD-L1 therapy, according to data from part B of the phase 2 TACTI-002 trial (NCT03625323).¹

The findings, presented as a part of a poster presentation at the 2022 World Conference on Lung Cancer, showed that LAG-3–targeted immunotherapy agent plus the anti–PD-1 monoclonal antibody produced a median OS of 9.7 months and an 18-month OS rate of 36.5%. The 6-month PFS rate was 25%.

“It is encouraging to see [eftilagimod alpha] in combination with pembrolizumab continues to report promising antitumor and safety results in second line [for] NSCLC,” Frédéric Triebel, MD, PhD, chief sales officer and chief medical officer at Immutep, stated in a press release. Immutep develops LAG-3 related immunotherapeutic products for to treat cancer and autoimmune diseases. “For patients with such advanced disease, having a chemo-free alternative could mean a very real difference to their quality of life.”

Part B of the non-randomized, multinational, open-label trial enrolled adult patients with a histologically or cytologically confirmed diagnosis of NSCLC after failure of first-line treatment of metastatic disease with at least 2 cycles of any PD-1/PD-L1–containing therapy alone or in combination with any other immunotherapeutic or chemotherapy.² Patients were also required to have an ECOG performance status of 0 or 1, plus a life expectancy of more than 3 months.

Patients were excluded from part B of the trial if they had symptomatic ascites or pleural effusion, received more than 1 line of chemotherapy for metastatic disease, or received more than 30 Gy lung radiation therapy within 6 months of the first dose of trial treatment.

Patients received 30 mg of subcutaneous eftilagimod alpha every 2 weeks for the first 8 cycles of treatment, then every 3 weeks for 9 cycles, for a total of 1 year. Patients also received 200 mg of intravenous pembrolizumab every 3 weeks for up to 2 years.

The primary end point of the trial was overall response rate (ORR). Secondary end points included OS, PFS, and other efficacy parameters, plus safety and tolerability.

All enrolled patients (n = 36) had confirmed progressive disease on or after first-line therapy with PD-1/PD-L1 monotherapy (33%) or a combination of PD-1/PDL1 therapy and platinum-based doublet chemotherapy (67%). Notably, 75% of patients had a PD-L1 tumor proportion score of less than 50%.

Additional data showed that the combination elicited an ORR of 5.6% (2/36) per iRECIST criteria in the intention-to-treat population. Both responses were partial and durable, each lasting more than 10 months. Moreover, 30.6% of patients achieved stable disease, 61.1% experienced disease progression, and 2.8% were not evaluable. The disease control rate was 36.1%.

The press release noted that eftilagimod alpha plus pembrolizumab continued to demonstrate safety and was well-tolerated, with no new safety signals.

“All these results support further clinical investigation of [eftilagimod alpha] in combination with pembrolizumab in [patients with PD-1/PD-L1]–resistant NSCLC,” Martin Forster, MD, a trial investigator and a medical oncologist at University College London Hospitals, said in a news release.

References

1. Immutep reports new positive interim data from its phase II study of LAG-3 candidate, eftilagimod alpha, in 2nd line PD-X refractory NSCLC. News release. Immutep. August 1, 2022. Accessed August 2, 2022. https://bit.ly/3JnIWPU
2. Combination study with soluble LAG-3 fusion protein eftilagimod alpha (IMP321) and pembrolizumab in patients with previously untreated unresectable or metastatic NSCLC, or recurrent PD-X refractory NSCLC or with recurrent or metastatic HNSCC (TACTI-002). ClinicalTrials.gov. Updated June 13, 2022. Accessed August 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03625323