FDA OKs Novel BiTE Agent for Small Cell Lung Cancer

The FDA has granted accelerated approval to tarlatamab (Imdelltra) as a second- or later-line option for patients with extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

Approval of the drug -- a first-in-class delta-like ligand 3 (DLL3)-targeting bispecific T-cell engager (BiTE) therapy -- was based on efficacy results from 99 patients enrolled in the phase II DeLLphi-301 trial.

Eligible patients were required to have relapsed/refractory SCLC with disease progression after receiving previous treatment with platinum-based chemotherapy and at least one other line of prior therapy. The trial excluded patients with symptomatic brain metastases, evidence of interstitial lung disease or noninfectious pneumonitis, and active immunodeficiency.

The overall response rate (ORR) with tarlatamab was 40% (38% partial response and 2% complete response), with a median duration of response of 9.7 months. Of the 69 patients with available data regarding platinum-sensitivity status, the ORR was 52% in platinum-resistant SCLC (progression in fewer than 90 days since the last platinum dose) and 31% in platinum-sensitive SCLC (progression after 90 days or more following the last dose).

"Lung cancer is a complex and devastating disease, and less than 3% of patients with [extensive-stage]-SCLC live longer than 5 years," said David P. Carbone, MD, PhD, of the James Thoracic Oncology Center at the Ohio State University Medical Center in Columbus, in a press release from drugmaker Amgen. "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."

As this indication was approved under the accelerated approval pathway based on ORR and duration of response, continued approval may be contingent upon results from confirmatory trials.

The most common adverse events (AEs) included cytokine release syndrome (CRS, 55%), fatigue (51%), pyrexia (36%), dysgeusia (36%), decreased appetite (34%), musculoskeletal pain (30%), constipation (30%), anemia (27%), and nausea (22%).

Serious AEs occurred in 58% of patients who received tarlatamab, the most common of which were CRS (24%), pneumonia (6%), pyrexia (3.7%), and hyponatremia (3.6%).

Common grade 3/4 laboratory abnormalities included decreased lymphocytes (57%), decreased sodium (16%), increased uric acid (10%), decreased total neutrophils (6%), decreased hemoglobin (5%), increased activated partial thromboplastin time (5%), decreased potassium (5%), increased aspartate aminotransferase (3.2%), decreased white blood cells (3.8%), decreased platelets (3.2%), and increased alanine aminotransferase (2.1%).

Prescribing information for tarlatamab includes a boxed warning for serious or life-threatening CRS and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome.

Tarlatamab is an intravenous drug recommended at an initial dose of 1 mg on day 1 followed by 10 mg on days 8 and 15 of cycle 1, then every 2 weeks thereafter until disease progression or unacceptable toxicity.

Correction: This article previously stated tarlatamab was approved as a third-line option; it has been approved as a second- or later-line option.

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