FDA Awards Fast Track Designation to Eftilagimod Alpha Plus Pembrolizumab in Frontline NSCLC

FDA

The FDA has granted a fast track designation to eftilagimod alpha (efti; IMP321) for use in combination with pembrolizumab (Keytruda) as a frontline treatment for patients with stage IIIB/IV non–small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) of at least 1%.¹

The designation was based on data from the phase 2 TACTI-002 trial (NCT03625323) that showed the combination of efti and pembrolizumab elicited an overall response rate (ORR) of 38.6% (95% CI, 29.6%-48.2%) by local read in the intent-to-treat (ITT) population (n = 114).² Additionally, among evaluable patients treated with the combination (n = 103), the ORR was 42.7% (95% CI, 33.0%-52.9%) by local read.

“We are pleased to receive this Fast Track designation as it acknowledges efti’s unique potential to empower the human immune system against cancer and significantly enhance patient responses to standard-of-care immunotherapy. Efti also offers a chemotherapy-free option for NSCLC patients in need of less toxic and more durable solutions,” Marc Voigt, chief executive officer of Immutep, stated in a press release.

“This important designation that efti has now received across two indications, first-line NSCLC and first-line head and neck squamous cell carcinoma [HNSCC], enables us to work more closely with the FDA to bring this novel treatment option to cancer patients in the most timely and efficient manner possible. We look forward to providing additional clinical data in first-line NSCLC later this year.”

Efti is a first-in-class antigen presenting cell (APC) activator for the treatment of cancer. Efti uses the unique characteristics of LAG-3 to activate both innate and adaptive immunity via binding to APCs such as dendritic cells, monocytes, and macrophages via MHC II molecules. By activating APCs, anti-tumor cells expand, antigens are presented to the adaptive immune system, and CD4+ and CD8+ T cells are amplified.

The TACTI-002 trial evaluated efti plus pembrolizumab as a first- or second-line treatment for patients with NSCLC, and for patients with HNSCC.³

Patients in first-line NSCLC cohort were required to have a histologically or cytologically confirmed diagnosis of stage IIIB NSCLC not amenable to curative treatment or stage IV NSCLC not amenable to EGFR/ALK-based therapy. Patients needed to be naïve for systemic therapy given for advanced/metastatic disease, though prior palliative radiotherapy for advanced/metastatic disease was acceptable. Patients also needed an ECOG performance status of 0 or 1, and a life expectancy of more than 3 months.

Key exclusion criteria for the first-line NSCLC cohort included the ability for patients to receive curative intent treatment with either surgical resection, chemoradiation, and/or radiation; prior systemic therapy for stage IV disease, unless the completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy occurred at least 6 months prior to the diagnosis of metastatic disease; the presence of an EGFR-sensitizing mutation or EML4/ALK gene fusions; or the prior lung radiation therapy of more than 30 Gy within 6 months of the first dose of trial treatment.

Enrolled patients received 30 mg of efti every 2 weeks for the first 8 cycles, then every 3 weeks starting in cycle 9, plus 200 mg of pembrolizumab every 3 weeks. Each cycle lasted 3 weeks.

The primary end point of the trial was ORR. Secondary end points consisted of time to response, duration of response (DOR), disease control rate, progression-free survival (PFS) overall survival, and safety.

Additional data showed that patients with a PD-L1 TPS of less than one (n = 32) experienced an ORR of 28.1%. Those with a PD-L1 TPS between 1% and 49% (n = 36) achieved an ORR of 41.7%. Patients with a PD-L1 TPS of at least 1% (n = 55) experienced an ORR of 45.5%, and those with a PD-L1 TPS of at least 50% (n = 19) had an ORR of 52.6%. Among all patients, the ORRs for patients with squamous and non-squamous disease were 35% and 38.9%, respectively.

Furthermore, 8.6% of confirmed responders experienced disease progression within 6 months, and the median DOR not yet reached. The interim median PFS was 6.9 months in the ITT, PD-L1 all-comers population. The interim median PFS was 8.4 months and 11.8 months for patients with a PD-L1 TPS of at least 1% and patients with a PD-L1 TPS of at least 50%, respectively.

The disease control rates in the ITT and evaluable patient populations were 73.7% and 81.6%, respectively.

Regarding safety, efti plus pembrolizumab was safe and well-tolerated, with 9.6% of patients in part A of the trial discontinuing due to study treatment-related adverse effects. The safety profile to date is consistent with that observed in previously reported studies for pembrolizumab monotherapy except for local injection site reactions.

References

1. Immutep receives FDA fast track designation for LAG-3 therapeutic eftilagimod alpha for first line non-small cell lung cancer. News release. Immutep. October 4, 2022. Accessed October 4, 2022. https://bit.ly/3C5MuTD
2. Immutep reports positive overall response rate in its phase II clinical trial in 1st line NSCLC for PD-L1 all-comers. News release. Immutep. June 4, 2022. Accessed October 4, 2022. https://bit.ly/3ygIY7F
3. 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 October 4, 2022. https://clinicaltrials.gov/ct2/show/NCT03625323