The first patient has been dosed in the phase 3 trial TACTI-004, which will evaluate efti (eftilagimod alfa), a first in class MHC Class 2 agonist, in combination with anti-PD-1 therapy Keytruda (pembrolizumab) and chemotherapy as first-line treatment for patients with advanced or metastatic non-small cell lung cancer, according to a news release from the drug’s manufacturer, Immutep.
“Despite advancements in the treatment landscape for non-small cell lung cancer, there remains a high unmet need for new approaches that can safely extend patients’ lives,” Dr. Ina Nordman, who treated the first patient at Calvary Mater Newcastle Hospital in Australia, stated in the release. “The anti-cancer immune response driven by efti’s unique mechanism of action as an MHC Class 2 agonist in combination with Keytruda has led to strong efficacy across all PD-L1 levels with favorable safety in multiple lung cancer trials. We hope to see this study confirm the promise of this novel combination to provide patients with a powerful new treatment option.”
Recruitment for TACTI-004 is progressing as more clinical sites and countries receive regulatory approvals, including Australia, Austria, Belgium, Bulgaria, Canada, Germany, Greece, Hungary, India, Ireland, Italy, Latvia, Lithuania, Portugal, Spain and the United Kingdom. Approvals in three more countries are expected soon, with additional clearances anticipated in the coming weeks and months.
TACTI-004 is a randomized, double-blind, controlled phase 3 trial evaluating efti with Keytruda and chemotherapy as a first-line treatment for advanced or metastatic non-small cell lung cancer without EGFR, ALK or ROS1 genomic tumor aberrations. The global trial will enroll about 756 patients, regardless of PD-L1 expression, with non-squamous or squamous tumors. Patients will be randomly assigned 1:1 to receive either efti with Keytruda and chemotherapy in the treatment arm or Keytruda with chemotherapy and a placebo in the control arm. The primary endpoints will include progression-free survival and overall survival.
Glossary:
MHC Class 2 agonist: a type of molecule that stimulates the immune system by activating MHC Class 2 receptors on antigen-presenting cells, enhancing the immune response against cancer cells.
Progression-free survival: the length of time during and after treatment that a patient lives with the disease without it getting worse.
Overall survival: the length of time from the start of treatment that patients are still alive, regardless of disease progression.
TPS: a biomarker used to measure the percentage of tumor cells expressing PD-L1. TPS greater than 1% indicates low expression of PD-L1, TPS 1 to 49% indicates moderate expression, and TPS greater than or equal to 50% indicates high expression of PD-L1.
“The ability of 30 milligram efti in combination with Keytruda to activate the immune system and fight non-small cell lung cancer regardless of PD-L1 expression has been demonstrated across multiple clinical trials,” Immutep chief scientific officer Dr. Frédéric Triebel, said in the release. “Importantly, this novel approach has an excellent safety profile while delivering strong efficacy that compares favorably to standard-of-care therapies, including high rates of durable responses and compelling progression-free survival and overall survival.”
According to the release, lung cancer is the leading cause of cancer-related death, with incidence expected to rise to about 3 million cases worldwide by 2030. Non-small cell lung cancer, the most common type, accounts for approximately 80% to 85% of all diagnoses. The disease is often detected at a late stage, and fewer than 30% of patients survive five years after diagnosis. There remains a significant need for additional treatment options for people with non-small cell lung cancer.
Previous TACTI-002 Trial
In the previous TACTI-002 trial, after a median follow-up of more than two years, the median overall survival was 35.5 months in first-line treatment of metastatic non-small cell lung cancer patients expressing PD-L1 (TPS [tumor proportion score] greater than 1%), 23.4 months in patients with low PD-L1 expression (TPS 1 to 49%) and had not been reached in patients with high PD-L1 expression (TPS greater than 50%), exceeding expectations.
Exceptional durability and quality of responses were demonstrated through overall survival and progression-free survival rates across patients expressing PD-L1, including three-year overall survival rates of 45.6% in TPS greater than 1%, 31% in TPS 1 to 49% and 63.6% in TPS greater than or equal to 50%.
Overall survival, overall response rate, progression-free survival and duration of response were observed across all PD-L1 subgroups (TPS less than 1%, greater than or equal to 1%, 1 to 49%, and greater than or equal to 50%), differentiating efti in combination with Keytruda from other chemotherapy-free immuno-oncology combinations in non-small cell lung cancer.
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