The FDA Grants Accelerated Approval to Tarlatamab-dlle in Small Cell Lung Cancer

The FDA has granted accelerated approval to tarlatamab-dlle (Imdelltra; Amgen Inc) to treat extensive stage small cell lung cancer (ES-SCLC) that has progressed during or after platinum-based chemotherapy treatment.¹

According to the National Cancer Institute, the prognosis for individuals diagnosed with SCLC is not optimal, despite treatment advancements over the past 25 years. If not treated, the median survival for SCLC is only 2 to 4 months. When treated, just 10% of individuals remain disease free during the 2 years from the start of treatment. The study authors noted that even among those who receive treatment, only 5% to 10% survive 5 years.²

Symptoms of SCLC can include inappropriate antidiuretic hormone secretion, Cushing syndrome from secretion of adrenocorticotropic hormone, paraneoplastic cerebellar degeneration, and Lambert-Eaton myasthenic syndrome, according to study authors.²

Tarlatamab is a first-in-class immunotherapy that binds to DLL3 tumor cells and CD3 T-cells, to kill DLL3-expressing SCLC, according to study authors.³

"After decades of minimal advancements in the SCLC treatment landscape, there is now an effective and innovative treatment option available," said Laurie Fenton Ambrose, co-founder, president, and CEO of GO2 for Lung Cancer, in a press release. "Today's FDA approval marks a significant milestone for the SCLC community as the availability of a targeted bispecific therapy brings forward new possibilities to those living with this aggressive disease."³

The accelerated approval was granted based on results from the DeLLphi-301 (NCT05060016) trial, an open-label, multicenter, multi-cohort study that assessed tarlatamab on 99 patients with ES-SCLC who experienced disease progression after platinum-based chemotherapy. The individuals received tarlatamab until signs of disease progression or unacceptable toxicity, according to study authors.¹ The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), according to study authors.¹

"In the DeLLphi-301 trial, the median overall survival was 14.3 months, with 40% of patients responding to treatment with tarlatamab. These responses were remarkably durable, representing a major advancement in the SCLC treatment paradigm," Ambrose said.³

Additionally, the study authors noted that the median DOR was 9.7 months.¹

The recommended initial dose of tarlatamab is an intravenous 1 mg infusion for 1 hour on cycle 1, day 1, then 10 mg on cycle 1 day 8 and 15, continued every 2 weeks.¹

The study authors noted that the most common adverse events included CRS, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.³

"The FDA's approval of IMDELLTRA marks a pivotal moment for patients battling ES-SCLC. This DLL3-targeting therapy in ES-SCLC comprises a transformative option demonstrating long-lasting responses in pretreated patients," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen, in a press release. “This approval further demonstrates our commitment to addressing aggressive cancers through our second FDA-approved Bispecific T-cell Engager (BiTE®) molecule. IMDELLTRA offers these patients who are in urgent need of new innovative therapies hope, and we're proud to deliver this long-awaited effective treatment to them."³

References

1. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. FDA. News release. May 16, 2024. Accessed May 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer.

2. Small Cell Lung Cancer Treatment (PDQ®)–Health Professional Version. National Cancer Institute. News release. March 1, 2024. Accessed May 17, 2024. https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq.

3. FDA Approves IMDELLTRA™ Tarlatamab-DLLE, The First and Only T-Cell Engager Therapy For The Treatment of Extensive Stage Small Cell Lung Cancer. PR Newswire. News release. May 16, 2024. Accessed May 17, 2024. https://www.prnewswire.com/news-releases/fda-approves-imdelltra-tarlatamab-dlle-the-first-and-only-t-cell-engager-therapy-for-the-treatment-of-extensive-stage-small-cell-lung-cancer-302148431.html.