Tarlatamab Shows Promise in Treating Extensive-Stage Small Cell Lung Cancer

New data presented at the World Conference on Lung Cancer (WCLC) 2024 highlights the potential of tarlatamab-dlle查看药品详情 (Imdelltra; Amgen查看公司主页) in treating extensive-stage small cell lung cancer (搜索)搜索该疾病 (ES-SCLC). The global phase 1b and phase 2 DeLLphi-303 study showcased a manageable safety profile, sustained disease control, and positive survival outcomes in patients with first-line maintenance ES-SCLC.

Tarlatamab-dlle查看药品详情, a bispecific T cell engager (BiTE), targets cancer cells by binding to both DLL3 (搜索)搜索该靶点 on cancer cells and CD3 on T cells, activating T cells to fight cancer. This mechanism leverages the toxicity of T cells to achieve a targeted immune response.

DeLLphi-303 Study: First-Line Maintenance Therapy

The phase 1b portion of the DeLLphi-303 study evaluated tarlatamab-dlle查看药品详情 combined with PD-L1 inhibitors as first-line maintenance therapy. The combination demonstrated a manageable safety profile, sustained disease control, and positive survival outcomes.

Key findings include:

• Tarlatamab-dlle plus a PD-L1 inhibitor: demonstrated a positive benefit: risk profile with no new or unexpected safety findings.
• Tarlatamab-dlle plus durvalumab: disease control rate (DCR) of 62.5% (95% CI: 45.8-77.3) and median duration of disease control (DoDC) that was Not Estimable (95% CI: 3.9, NE).
• Tarlatamab-dlle plus atezolizumab: DCR of 62.5% (95% CI: 47.4-76.0) and median DoDC of 7.2 months (95% CI: 5.6, NE).
• Following a median time of 3.5 months from first-line chemoimmunotherapy to first-line maintenance:
  • Tarlatamab-dlle plus durvalumab showed a 9-month overall survival (OS) of 91.8% (95% CI: 76.6-97.3) and median progression-free survival (mPFS) of 5.3 months (95% CI: 3.5-NE).
  • Tarlatamab-dlle plus atezolizumab showed a 9-month OS of 86.7% (95% CI: 70.3-94.4) and mPFS of 5.6 months (95% CI: 3.5-8.5).

Sally Lau, MD, assistant professor of medicine at Perlmutter Cancer Center, NYU Grossman School of Medicine, noted, "Tarlatamab has been a major breakthrough for patients with [ES-SCLC], who have had limited options for the past 30 years, and these data are impressive as a potential first-line maintenance treatment as well."

DeLLphi-301 Study: Extended Follow-Up Data

The phase 2 DeLLphi-301 study, with extended follow-up data, included patients with ES-SCLC previously treated with platinum-based chemotherapy. The results showed continued anticancer activity with a manageable safety profile. Among 100 enrolled patients, the median overall survival (OS) was 15.2 months, and the objective response rate (ORR) was 40%.

Regulatory Approval and Clinical Significance

Earlier this year, the FDA granted accelerated approval to tarlatamab-dlle查看药品详情 for ES-SCLC that has progressed during or after platinum-based chemotherapy. This approval was based on the DeLLphi trial, where patients received the drug until disease progression or unacceptable toxicity. The investigators observed a median OS of 14.3 months, with 40% of patients responding to tarlatamab-dlle. The median duration of response (DOR) was 9.7 months.

Safety and Tolerability

In the DeLLphi-303 study, treatment-related adverse events (TRAEs) led to dose interruptions in 15% of patients receiving tarlatamab-dlle查看药品详情 plus durvalumab查看药品详情 and 17% in the atezolizumab查看药品详情 arm. Cytokine release syndrome (搜索)搜索该疾病 (CRS) was mostly grade 1-2, occurring primarily in cycle 1 and generally manageable with supportive care. Immune effector cell-associated neurotoxicity syndrome (搜索)搜索该疾病 (ICANS) was infrequent overall.

Ongoing Research and Future Directions

Tarlatamab is currently being investigated in multiple studies, including the phase 3 DeLLphi-305 trial, which compares tarlatamab in combination with durvalumab查看药品详情 versus durvalumab alone as first-line maintenance treatment in ES-SCLC. These ongoing trials aim to further define the role of tarlatamab in treating small cell lung cancer (搜索)搜索该疾病 and improving patient outcomes.