Nonchemotherapy doublet shows therapeutic potential in PD-1/PD-L1 inhibitor‒resistant NSCLC

Combination treatment with eftilagimod alpha plus pembrolizumab has shown promising signal of activity against metastatic nonsmall cell lung cancer (NSCLC) in patients resistant to PD-1/PD-L1 inhibitors, as shown in the updated results of the phase II TACTI-002 study.

In a cohort of 36 patients, the combination was associated with an objective response rate (ORR) of 8.3 percent and a disease control rate (DCR) of 33 percent, reported lead investigator Dr Margarita Majem of the Hospital of the Holy Cross and Saint Paul in Barcelona, Spain, at ELCC 2023.

For the vast majority of patients, tumour growth slowed (50 percent) or the target lesions shrunk (33 percent), Majem added.

The median progression-free survival (PFS) was 2.1 months, with a 6-month PFS rate of 25 percent. A total of 44 percent and 39 percent of patients were alive at 12 and 21 months, respectively, with a median overall survival (OS) of 9.9 months. [ELCC 2023, abstract 11MO]

A subgroup analysis indicated that patients with high PD-L1 expression or secondary resistance had notably better ORR, PFS, and OS than patients with PD-L1 negative expression or primary resistance.

The 21-month OS rate of 39 percent with eftilagimod alpha plus pembrolizumab compares favourably to historical data, with docetaxel being associated with a 21-month OS rate of 10–15 percent, according to Majem Tarruella. [N Engl J Med 2015;373:123-135; N Engl J Med 2015;373:1627-1639]

In terms of safety, the combination was found to be well tolerated, with no new safety signals reported. The most common adverse events were as follows: decreased appetite (33 percent), dyspnoea (31 percent), cough (28 percent), asthenia (22 percent), fatigue (19 percent), arthralgia (17 percent), and weight loss (17 percent).

“Eftilagimod alpha is a soluble LAG-3 protein that acts as an MHC class II agonist triggering the activation of APC and CD8 T-cells,” Majem said.

Taken together, the TACTI-002 data suggest that the addition of the APC activator eftilagimod alpha to anti-PD-1 therapy may revert resistance to anti-PD-1/PD-L1 therapy, warranting further investigation, she added.

Of the patients included in the study, 19 percent had squamous and 78 percent had nonsquamous histology. Their median age was 67 years, and 61 percent were men. ECOG Performance Score was 0 in 33 percent of patients and 1 in 67 percent.

Overall, the patients had resistance to first-line PD-1/PD-L1 inhibitor-based therapy and were treated with subcutaneous eftilagimod alpha (30 mg once every 2 weeks, then once every 3 weeks starting cycle 9) and intravenous pembrolizumab (200 mg once every 3 weeks for 1 year), and then 1 year of pembrolizumab alone. The median doses of pembrolizumab and eftilagimod alpha received were 5 and 7, respectively.