The U.S. Food and Drug Administration has granted full approval to Amgen's Imdelltra (tarlatamab-dlle) for the treatment of adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. The decision converts Imdelltra's prior accelerated approval to full approval based on confirmatory data from the global Phase 3 DeLLphi-304 study.
Significant Survival Benefit Demonstrated
The DeLLphi-304 study met its primary endpoint, demonstrating that Imdelltra reduced the risk of death by 40% compared to standard of care chemotherapy. The treatment significantly extended median overall survival by more than five months (13.6 vs. 8.3 months; hazard ratio 0.60; 95% confidence interval: 0.47, 0.77; P < 0.001).
"The FDA's decision reinforces IMDELLTRA as a recognized standard of care for people living with extensive stage small cell lung cancer whose disease progressed on or after frontline therapy," said Jay Bradner, executive vice president of research and development at Amgen.
NCCN Guidelines Recognition
The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology were recently updated to include tarlatamab as the only Category 1 preferred treatment option for adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy.
"After years of research efforts, DeLLphi-304 was the first global Phase 3 trial to demonstrate a significant survival benefit over chemotherapy in its setting, leading to NCCN Guidelines Category 1 status for tarlatamab," said Charles M. Rudin, deputy director at Memorial Sloan Kettering Cancer Center and principal investigator.
Improved Safety Profile
The safety profile for Imdelltra in DeLLphi-304 was consistent with its known profile, with fewer Grade 3 or greater adverse events in the Imdelltra arm compared to the chemotherapy arm (54% vs 80%). The most common Grade 3 or greater treatment-related adverse events were neutropenia (4%) and lymphopenia (4%) with Imdelltra, compared to anemia (28%) and neutropenia (22%) with standard chemotherapy.
Cytokine release syndrome (CRS) with Imdelltra primarily occurred after the first two doses and was primarily low grade (42% Grade 1; 13% Grade 2; 1% Grade 3). No Grade 4 or Grade 5 CRS events were reported.
Novel Mechanism of Action
Imdelltra is a first-in-class targeted immunotherapy engineered to bind to both DLL3 on tumor cells and CD3 on T cells, thereby activating T cells to kill DLL3-expressing SCLC cells. DLL3 is a protein expressed on the surface of SCLC cells in approximately 85-96% of patients with SCLC, but is minimally expressed on healthy cells.
Addressing Critical Unmet Need
Small cell lung cancer is one of the most aggressive forms of solid tumor cancers, with a five-year relative survival rate of only 5-10% across all stages combined in the United States. Each year, SCLC accounts for approximately 13-15% of the more than 2.4 million cases of lung cancer diagnosed worldwide, including around 227,000 cases in the United States.
"For far too long, people living with small cell lung cancer had few options once their first treatment stopped working," said Laurie Fenton Ambrose, co-founder, president, and CEO of GO2 for Lung Cancer. "Today's full approval is an important step forward, reinforcing long-awaited progress for patients facing this devastating disease."
Comprehensive Development Program
The DeLLphi-304 study was a global Phase 3, randomized, controlled, open-label clinical trial that enrolled 509 patients who were randomized to receive either Imdelltra or local standard of care chemotherapy. The study evaluated patients with SCLC who progressed on or after a single line of platinum-based chemotherapy.
Amgen's robust Imdelltra development program includes multiple DeLLphi clinical trials evaluating the drug as monotherapy and in combination regimens, including studies in earlier stages of SCLC and earlier lines of treatment. The company is currently focused on rapidly developing Imdelltra in earlier stages of disease and earlier lines of therapy for small cell lung cancer patients.
