The TACTI-002 study's encouraging ORR of 38.6%, along with impressive responses across all PD-L1 status groups, shows that efti may induce an anti-tumor immune response even in patients with minimal or low PD-L1 expression (Abstract # 9003)
LAG-3 is a new targetable immune checkpoint that has garnered the interest of oncologists and pharmaceutical companies. Since the mechanism of action of LAG-3 inhibitors is to prevent the suppression of T-cells, which is the same as that of PD-1/L-1 and CTLA-4 inhibitors, the LAG-3 inhibitors are also expected to demonstrate good results.
According to data presented in an oral presentation at the American Society of Clinical Oncology’s (ASCO) 2022 annual meeting, the study met the primary endpoint of Overall Response Rate (ORR) as of the data cut-off date of 15 April 2022. For the intent-to-treat population, the ORR by local read was 38.6%, and for evaluable patients, it was 42.7%. A comparable ORR is reported in both squamous and non-squamous tumor types (35% and 38.9%, respectively). Furthermore, compared to previous studies of anti-PD-1 monotherapy for all-comers and PD-L1 status groups, ORR appeared to be positive. Responses are also long-lasting, with just 8.6% of confirmed responses progressing after 6 months, with the median duration of response (DoR) not yet attained. The interim median Progression-Free Survival (PFS) is 6.9 months (ITT, PD-L1 all-comers). The Disease Control Rate (DCR) in the intent-to-treat group is 73.7%, whereas the DCR for evaluable patients is 81.6%.
The combination of eftilagimod alpha with pembrolizumab is safe and well-tolerated. Part A reports a low discontinuation rate, with just 9.6% of participants dropping out due to study therapy's adverse events. Except for local injection site responses, the safety profile to date is similar to that found in previously published trials for pembrolizumab monotherapy (erythema).
“It is very encouraging to see the combination of efti plus pembrolizumab is showing favourable anti-tumour activity in patients with 1st line NSCLC. These responses were deep and durable and there has also been a low patient discontinuation rate. I believe the combination of efti plus pembrolizumab warrants late-stage clinical investigation.”–Expert Opinion.
Conclusion
Looking at the present NSCLC emerging clinical landscape, several studies are exploring various therapies alone or in combination with other therapies. Most novel medicines are being developed in combination with PD-1/PD-L1, hoping that the combination approach will provide a favorable response in cancer patients. Now that Bristol Myers Squibb's first LAG-3 Relatlimab has been approved by the United States Food and Drug Administration (FDA) and clouds are soaring above TIGIT-targeted therapies, now is the moment to engage with LAG-3 directed assets. The failure of anti-TIGIT Tiragolumab in the SKYSCRAPER-02 and SKYSCRAPER-01 late-stage trials has been upsetting to Roche and oncology professionals as well. It will be interesting to see if eftilagimod alpha in combination with pembrolizumab will become the next immunotherapy to enter the NSCLC space in the future.
