On May 16, 2024, tarlatamab-dlle (Imdelltra) was granted accelerated approval for extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.1 Tarlatamab is a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager.
Supporting Efficacy Data
KEY POINTS
- Tarlatamab-dlle was granted accelerated approval for extensive-stage SCLC with disease progression on or after platinum-based chemotherapy.
- The recommended tarlatamab dose is an initial dose of 1 mg on cycle 1, day 1, followed by 10 mg on cycle 1, days 8 and 15, then every 2 weeks thereafter until disease progression or unacceptable toxicity.
Approval was based on findings in the DeLLphi-301 study (ClinicalTrials.gov identifier NCT05060016), in which 99 evaluable patients with disease progression following platinum-based chemotherapy received intravenous tarlatamab at an initial dose of 1 mg on cycle 1, day 1, followed by 10 mg on days 8, 15, and every 2 weeks thereafter until disease progression or unacceptable toxicity. Patients with symptomatic brain metastases, interstitial lung disease or noninfectious pneumonitis, or active immunodeficiency were excluded from the trial.
Objective responses on blinded independent central review were observed in 40 patients (40%, 95% confidence interval [CI] = 31%–51%), with a complete response in 2 (2%). The median response duration was 9.7 months (range = 2.7 to 20.7+ months), with 68% and 40% of responses lasting ≥ 6 and ≥ 12 months. Among 69 patients with available platinum sensitivity status, the objective response rates were 52% in 27 with platinum-resistant disease and 31% in 42 with platinum-sensitive disease.
How It Is Used
The recommended tarlatamab dose is an initial dose of 1 mg on cycle 1, day 1, followed by 10 mg on cycle 1, days 8 and 15, then every 2 weeks thereafter until disease progression or unacceptable toxicity. Product labeling provides instructions on concomitant medications and management of cytokine-release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS).
Safety Profile
OF NOTE
Tarlatamab-dlle has a boxed warning for cytokine-release syndrome and neurologic toxicity including ICANS.Safety data are from 187 patients with extensive-stage SCLC who received tarlatamab in the DeLLphi-300 and DeLLphi-301 studies. The most common adverse events of any grade were cytokine-release syndrome (55%, 1.6% grade 3 or 4), fatigue (51%), pyrexia (36%), and dysgeusia (36%). The most common grade 3 or 4 adverse events included anemia (6%) and decreased appetite (3%). The most 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, most commonly cytokine-release syndrome (24%), pneumonia (6%), pyrexia (4%), and hyponatremia (4%). Adverse events led to discontinuation of treatment in 7%, including cytokine-release syndrome (2%), and tumor-lysis syndrome (1%). Fatal adverse events occurred in 2.7% of patients, including (0.5% each) pneumonia, aspiration, pulmonary embolism, respiratory acidosis, and respiratory failure.
Tarlatamab-dlle has a boxed warning for cytokine-release syndrome and neurologic toxicity including ICANS. Tarlatamab also has warnings/precautions for cytopenias, infections, hepatotoxicity, hypersensitivity, and embryofetal toxicity. Patients should not breastfeed while receiving tarlatamab-dlle.
REFERENCE
1. Tarlatamab-dlle (Imdelltra) for injection, for intravenous use, prescribing information, Amgen, Inc, 2024. Available at https://www.accessdata.fda.gov. Accessed May 31, 2024.
