Article

Second-Line Eftilagimod Alpha Plus Pembrolizumab Shows Promising Activity in Metastatic Lung Cancer

Author(s):

The combination of eftilagimod alpha and pembrolizumab was found to produce an encouraging early overall survival rate of 73% at the 6-month landmark when used as second-line treatment in patients with PD-1/PD-L1–refractory, metastatic non–small cell lung cancer, according to data from part B of the phase 2 TACTI-002 trial.

Matthew G. Krebs, MB, ChB, FRCP, PhD

Matthew G. Krebs, MB, ChB, FRCP, PhD

The combination of eftilagimod alpha (IMP321) and pembrolizumab (Keytruda) was found to produce an encouraging early overall survival (OS) rate of 73% at the 6-month landmark when used as second-line treatment in patients with PD-1/PD-L1–refractory, metastatic non–small cell lung cancer, according to data from part B of the phase 2 TACTI-002 trial (NCT03625323).1

The doublet elicited an overall response rate (ORR) of 5.6% per iRECIST criteria among 36 patients in the intention-to-treat (ITT) population, which included a partial response (PR) rate of 5.6%. The 2 responders demonstrated deep and durable responses to treatment. Moreover, 30.6% of patients achieved stable disease, 61.1% experienced disease progression, and 2.8% were not evaluable. The disease control rate (DCR) in this population was 36.1%.

In 35 evaluable patients, the ORR produced with eftilagimod alpha/pembrolizumab was 5.7%, and the DCR was 37.1%.

“These interim results show an encouraging DCR of 36.1% with 26% of patients being progression free at the 6-month landmark,” Matthew G. Krebs, MB, ChB, FRCP, PhD, of The University of Manchester and The Christie NHS Foundation Trust, stated in a press release.2 “These patients are a challenging population to treat, having progressed after previous lines of immunotherapy or chemoimmunotherapy and have limited options available for further treatment. So, it is pleasing to see the potential that eftilagimod alpha in combination with pembrolizumab has to provide meaningful benefit in this patient group.”

A soluble LAG-3 protein that binds to a subset of MHC class II molecules, eftilagimod alpha mediates antigen-presenting cell and CD8 T-cell activation in patients. By stimulating the dendritic cell network, T cells are recruited; this could result in more potent antitumor responses when paired with pembrolizumab compared with what has been reported with the PD-1 inhibitor by itself.

Part B of the non-randomized, multinational, open-label, phase 2 trial included patients with PD-1/PD-L1–refractory, metastatic, PD-L1 all-comer NSCLC who previously received treatment in the frontline setting. The trial had a Simon’s two stage design.

Study participants received eftilagimod alpha via subcutaneous injection at 30 mg every 2 weeks for the first 8 cycles of treatment, and then every 3 weeks for the 9 cycles thereafter. The agent was given for a total of 1 year. Intravenous pembrolizumab was received at a dose of 200 mg every 3 weeks for up to 2 years. For cycles 19 through 35, patients received pembrolizumab alone, given every 3 weeks.

The primary end point of the trial was ORR per iRECIST criteria, and secondary end points included progression-free survival and other efficacy parameters, safety and tolerability, as well as exploratory biomarker analyses. The database cutoff date was January 21, 2022, with a minimum follow-up of over 5 months.

The median age among the 36 patients enrolled to the trial was 67 years (range, 46-84), and 61.1% were male. Moreover, 66.7% had an ECOG performance status of 1, 86.1% were current or ex-smokers, and all had received previous PD-1/PD-L1 therapy; 72.2% also received prior chemotherapy. Most patients (77.8%) had nonsquamous pathology, 19.4% had squamous disease, and 2.8% had unknown histology. Approximately 11% of patients (11.1%) had liver metastasis.

Regarding tumor resistance, which was defined according to SITC Immunotherapy Resistance Taskforce consensus, 66.7% had secondary resistance and 30.6% had primary resistance. Regarding PD-L1 tumor proportion score (TPS), 36.1% had a score of less than 1%, 33.3% had a score ranging from 1% to 49%, 19.4% had a score that was 50% or higher, and 11.1% were not evaluable.

Additional findings presented during the 2022 ESMO European Lung Cancer Conference indicated that 73.7% of patients experienced post-treatment tumor shrinkage or tumor growth deceleration, according to tumor growth kinetics analysis. The median OS had not yet been reached. Six patients were still receiving treatment on the trial at the data cutoff date.

Data on 2 case studies were also shared as part of the poster presentation. The first case was a 71-year-old female who had been diagnosed with metastatic, nonsquamous NSCLC in September 2016. This patient was given carboplatin in combination with pemetrexed in the frontline setting for the duration of 18 months; they stopped treatment due to disease progression.

At the time of study entry, the patient had an ECOG performance status of 1, were not evaluable for PD-L1 TPS, her tumor did not harbor an EGFR mutation or ALK aberration, and she was an ex-smoker. She joined the study in February 2020 and was still on treatment as of January 2022, with a confirmed ongoing PR.

The second case was a 67-year-old female who, in August 2019, had been diagnosed with metastatic, nonsquamous NSCLC. For her first-line treatment, she received cisplatin plus pemetrexed in combination with pembrolizumab for the duration of 8 months. She experienced disease progression and discontinued treatment.

She entered the study in April 2021, and at that time, she had an ECOG performance status of 0 and a PD-L1 TPS of 80%. Her tumor was EGFR/ALK negative, she was a non-smoker, and she had several metastatic sites, including the lung and lymph nodes. This patient was still on the study treatment as of January 2022, with a confirmed PR.

Study participants received a median of 5 (range, 2-31) pembrolizumab administrations and a median of 7 (range 2-22) eftilagimod alpha administrations.

Regarding safety, the combination was found to be well tolerated. The treatment-emergent adverse effects that were most frequently experienced with the regimen included dyspnea (33.3%), reduced appetite (33.3%), and cough (25%). Notably, no treatment-related deaths were reported.

References

  1. Krebs MG, Majem M, Forster M, et al. Results from a phase II study investigating eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in 2nd line PD-1/PD-L1 refractory metastatic non-small cell lung carcinoma (NSCLC) patients. Presented at: 2022 ESMO European Lung Cancer Conference; March 30-April 2, 2022; virtual. Accessed March 31, 2022. https://bit.ly/3755Kof
  2. Immutep’s efti in combination with MSD’s pembrolizumab shows encouraging antitumor activity in difficult to treat 2nd line metastatic lung cancer patients. News release. Immutep Limited; March 30, 2022. Accessed March 31, 2022. https://bit.ly/3iRZVNW
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