First-in-Class Tarlatamab Receives FDA Approval for Small Cell Lung Cancer

In patients whose disease progressed during or after platinum-based chemotherapy, treatment of extensive-stage small cell lung cancer (SCLC) with tarlatamab-dlle (Imdelltra, Amgen, Inc.) received accelerated FDA (United States Food and Drug Administration) approval on May 16, 2024.

The First Bispecific Drug in Its Class

A first-in-class bispecific drug represents an entirely new type of medicine, not previously developed with similar mechanisms or targets. Tarlatamab-dlle is the first drug able to bind simultaneously to DLL3 on tumor cells and CD3 on immune cells. It thereby aims to activate immunity to destroy tumor cells. This dual-target approach may offer greater effectiveness and fewer side effects than conventional treatments. In this sense, tarlatamab is considered a targeted therapy .

Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 (DLL3) on the surface of cells, including tumor cells, and CD3 expressed on T cells. This interaction causes T-cell activation, release of inflammatory cytokines, and destruction of DLL3-expressing cancer cells.

FDA Approval Based on the DeLLphi-301 Trial

Efficacy was evaluated in 99 patients with relapsed/refractory extensive-stage SCLC whose disease had progressed after platinum-based chemotherapy and who were enrolled in DeLLphi-301, an open-label, multicenter, multicohort study.

Patients with symptomatic brain metastases, interstitial lung disease or noninfectious pneumonitis, and active immunodeficiency were excluded. Tarlatamab was given until disease progression or unacceptable toxicity.

The main efficacy measures were overall response rate (ORR) and duration of response.

• The overall response rate was 40% (95% CI: 31, 51), and among responders, median response duration was 9.7 months (range 2.7, 20.7+).

Among the 69 patients with available platinum sensitivity data, the overall response rates were:

• 52% (95% CI 32, 71) in 27 patients with platinum-resistant SCLC, defined as progression within < 90 days after the last platinum dose, and
• 31% (95% CI 18, 47) in 42 patients with platinum-sensitive SCLC, defined as progression ≥ 90 days after the last platinum dose.

The prescribing information for tarlatamab-dlle includes a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). The most common adverse reactions, occurring in more than 20%, were CRS, fatigue, fever, dysgeusia (altered taste), decreased appetite, musculoskeletal pain, constipation, anemia, and nausea. The most common Grade 3 or 4 laboratory abnormalities (≥5%) were decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.

The recommended tarlatamab dose is an initial 1 mg intravenous infusion over 1 hour on Cycle 1 Day 1, followed by 10 mg on Cycle 1 Days 8 and 15, and then every 2 weeks until disease progression or unacceptable toxicity.