The U.S. Food and Drug Administration (FDA) has granted accelerated approval to tarlatamab-dlle (Imdelltra) for the treatment of adult patients with extensive-stage small cell lung cancer (SCLC) who have experienced disease progression on or after platinum-based chemotherapy. Tarlatamab, a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager, offers a new therapeutic option for patients with this aggressive cancer.
The approval was primarily based on the results of the DeLLphi-301 study (NCT05060016), a clinical trial evaluating the efficacy and safety of tarlatamab in previously treated patients with extensive-stage SCLC. The study enrolled patients who had progressed following platinum-based chemotherapy and excluded those with symptomatic brain metastases, interstitial lung disease, or active immunodeficiency.
Efficacy Data from DeLLphi-301
The DeLLphi-301 study involved 99 evaluable patients who received intravenous tarlatamab at an initial dose of 1 mg on cycle 1, day 1, followed by 10 mg on days 8 and 15, and then every 2 weeks until disease progression or unacceptable toxicity. Blinded independent central review showed an objective response rate of 40% (95% CI = 31%–51%), with a complete response rate of 2%. The median duration of response was 9.7 months (range = 2.7 to 20.7+ months), with 68% and 40% of responses lasting ≥ 6 and ≥ 12 months, respectively.
Further analysis based on platinum sensitivity status revealed objective response rates of 52% in patients with platinum-resistant disease (n=27) and 31% in those with platinum-sensitive disease (n=42).
Dosage and Administration
The recommended dose of tarlatamab involves an initial dose of 1 mg on cycle 1, day 1, followed by 10 mg on cycle 1, days 8 and 15, and then every 2 weeks thereafter until disease progression or unacceptable toxicity. The prescribing information includes guidance on concomitant medications and the management of cytokine-release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS).
Safety Profile and Adverse Events
The safety profile of tarlatamab was evaluated in 187 patients with extensive-stage SCLC across the DeLLphi-300 and DeLLphi-301 studies. Common adverse events of any grade included cytokine-release syndrome (55%, 1.6% grade 3 or 4), fatigue (51%), pyrexia (36%), and dysgeusia (36%). Grade 3 or 4 adverse events included anemia (6%) and decreased appetite (3%). Common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (57%), decreased sodium (16%), and decreased neutrophils (6%).
Serious adverse events occurred in 58% of patients, with cytokine-release syndrome (24%), pneumonia (6%), pyrexia (4%), and hyponatremia (4%) being the most frequent. Adverse events led to treatment discontinuation in 7% of patients, including cytokine-release syndrome (2%) and tumor-lysis syndrome (1%). Fatal adverse events occurred in 2.7% of patients.
Tarlatamab carries a boxed warning for cytokine-release syndrome and neurologic toxicity, including ICANS. Warnings and precautions also address cytopenias, infections, hepatotoxicity, hypersensitivity, and embryofetal toxicity. Breastfeeding is contraindicated during tarlatamab treatment.
