Immunotherapy combo shows promising efficacy as first-line treatment for NSCLC
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The addition of eftilagimod alpha to pembrolizumab conferred a 40% overall response rate among patients with non-small cell lung cancer unselected for PD-L1, a cohort analysis of the phase 2 TACTI-002 trial showed.
Results of the study, presented during Society for Immunotherapy of Cancer Annual Meeting, suggest that first-line treatment with the combination is safe and validate movement into late-stage clinical study, the investigators noted.
Background
Eftilagimod alpha (Immutep) is a soluble lymphocyte activation gene 3 (LAG-3) agonist that binds to a subset of major histocompatibility complex class II molecules to facilitate antigen-presenting cell activation and recruitment and activation of CD4 and CD8 T cells.
By stimulating antigen-presenting cells with eftilagimod alpha, researchers hope to recruit more T cells as part of the body’s antitumor response to pembrolizumab (Keytruda, Merck) — a PD-1 inhibitor.
The approach aims to produce better results than using pembrolizumab alone, especially in patients who express lower levels of PD-L1, according to Wade T. Iams, MD, assistant professor of medicine in the division of hematology/oncology at Vanderbilt University Medical Center.
“Eftilagimod alpha uses a novel mechanism to target LAG-3 that results in antigen-presenting cell priming upstream of T-cell cytotoxic killing,” Iams said during a presentation. “Combining pembrolizumab and the cytotoxicity associated with antigen-presenting cell priming can add to the antitumor efficacy [of pembrolizumab alone].”
Methodology
Iams and colleagues reported results from a cohort of patients in the TACTI-002 trial comprising participants with previously untreated unresectable or metastatic NSCLC.
The analysis included 114 patients (median age, 67 years; range, 44-85; 74% male) unselected for PD-L1 and enrolled between March 2019 and November 2021.
Among the patients, 40 (35.1%) had squamous cell carcinoma and 72 (63.2%) had non-squamous cell carcinoma. Nearly all patients (99.1%) had metastatic disease, and 94.7% had been smokers or currently smoked.
Approximately 75% of patients had PD-L1 tumor proportion score of less than 50%.
Study participants received subcutaneous eftilagimod alpha dosed at 30 mg once every 2 weeks for eight cycles, with each cycle lasting 3 weeks. Patients then received eftilagimod alpha 30 mg once every 3 weeks in combination with IV pembrolizumab 200 mg for nine cycles, followed by pembrolizumab 200 mg once every 3 weeks for 16 cycles.
ORR according to iRECIST evaluation served as the study’s primary endpoint.
“We were aiming for a goal of a historical response rate in the first-line setting of up to 35%,” Iams said.
Secondary endpoints included ORR by RECIST 1.1, ORR by blinded independent central review, duration of response, PFS, OS, safety and tolerability.
Each patient had minimum follow-up of at least 7 months, with a data cutoff point of July 1, 2022.
Key findings
The trial met its primary endpoint, with an ORR of 40.4% (95% CI, 31.3-50) in the intent-to-treat population. Forty-five patients (39.5%) had a partial response to therapy and 37 (32.5%) had stable disease.
One patient (0.9%) had a complete response to the combination therapy.
ORRs appeared similar via RECIST 1.1 evaluation (38.6%; 95% CI, 29.6-48.2) and blinded independent review (43.6%; 33.7-53.8).
Investigators observed responses to therapy across all PD-L1 subgroups, with a stepwise increase in response rates with increasing levels of PD-L1 expression.
Researchers reported a median duration of response of 21.6 months (95% CI, 17.3-30), median PFS of 6.6 months (95% CI, 4.6-9.3) and a 6-month PFS rate of 56.2%.
Approximately a quarter of patients had grade 1 or grade 2 injection site reactions to eftilagimod alpha administration, Iams noted. No grade 3 or higher injection site reactions occurred.
Three patients died during the study; investigators could not rule out treatment with either study drug as a contributing cause of death.
The most common treatment-related adverse events included pruritus (20.2%), asthenia (19.3%) and rash (13.2%).
Clinical implications
The addition of eftilagimod alpha to pembrolizumab has thus far shown encouraging results in patients with previously untreated NSCLC who are not candidates for targeted therapy, Iams said.
“We saw deep and durable responses across all PD-L1 subgroups,” he added.
“Overall response and progression-free survival in our study are [promising] compared with historical controls, especially for patients with tumors that have little or no PD-L1 expression,” Iams said. “The combination of eftilagimod alpha and pembrolizumab is safe and tolerable, and there are ongoing studies in late-stage development for this combination.”
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Iams W, et al. Abstract 1470. Presented at: Society for Immunotherapy of Cancer Annual Meeting; Nov. 8-12, 2022; Boston.
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