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The incidence of small cell lung cancer (SCLC) has significantly dropped in recent decades with the decline in cigarette smoking. Still, the aggressive nature and widespread metastases that characterize this disease continue to limit treatment success for those plagued by their diagnosis. SCLC is more responsive to chemotherapy and radiation treatments than other lung cancers, yet the prognosis remains poor, with survival rates as low as 2% in patients with disseminated disease at the time of diagnosis. 

Tarlatamab: A Promising New Treatment

The medical team at the University of Maryland Medical System (UMMS) is working to extend survival for these patients using tarlatamab, the first bispecific T-cell engager (BiTE) therapy agent approved by the Food and Drug Administration (FDA) for solid tumor malignancy. Since its accelerated FDA approval in May 2024, this drug has shown “better outcomes than previous treatment options,” says Katherine Scilla, MD, FACP, assistant professor of medicine at the University of Maryland School of Medicine and Medical Oncologist at the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC). Dr. Scilla highlights tarlatamab’s “ability for intracranial activity, which is important because a significant proportion of patients with SCLC develop brain metastases during their disease course.”

How It Works

Tarlatamab works by binding to the protein DLL3 on SCLC tumor cells and the protein complex CD3 on immune system T-cells, resulting in cancer cell death. The DeLLphi-301 trial demonstrated an overall response rate of 40%, a median duration response of 9.7 months, and a median overall survival of 14.3 months in trial participants who received the FDA-approved dosage of tarlatamab. According to Samuel Rosner, MD, assistant professor of medicine at the University of Maryland School of Medicine and thoracic oncologist at UMGCCC, “A phase III clinical trial, DeLLphi-304, is underway to directly compare tarlatamab with other approved second-line therapies, confirming DeLLphi-301’s promising results.” 

Common Side Effects

Patients taking tarlatamab may experience common side effects like changes in taste, decreased blood counts, and fatigue. Of greatest concern are the potentially life-threatening immune-related side effects associated with this drug, specifically cytokine release syndrome (CRS) and neurologic toxicity. 

  • CRS, an inflammatory response within the body, is characterized by fevers, unstable blood pressure, and respiratory issues.
  • Immune effector cell-associated neurotoxicity (ICANS) can cause various neurologic side effects, including headaches, decreased consciousness, and weakness.

Side Effect Management

“There are reversal medications available for both CRS and ICANS to help alleviate symptoms, but they require prompt identification and treatment initiation,” explains Dr. Rosner. “An inpatient hospital stay of 22-24 hours is required for each of the first two treatments,” when severe side effects are most likely to occur. UMGCCC was one of the first facilities in Maryland to offer this therapy option; therefore, team members have “a great deal of experience with BiTE therapies and immune-related side effects,” says Dr. Scilla. Dr. Rosner emphasizes the need for an experienced medical team familiar with using these agents “to ensure that encountered toxicities are safely and appropriately addressed.”

Patient Referrals

The UMGCCC team members work closely with referring physicians to determine patient eligibility and coordinate the initiation of tarlatamab treatment at UMMS facilities. Patients with SCLC that has progressed after prior chemotherapy plus immunotherapy combination may be eligible to receive this new therapy. Unlike other immunotherapies, no protein marker testing is required prior to initiating treatment since DLL3 is highly expressed in SCLC cells. Patients referred for treatment will receive individualized care, including an assessment by a thoracic oncologist and 1:1 patient education from the thoracic nurse coordinator. “In addition to providing access to tarlatamab treatment, we offer several exciting clinical trials for previously treated SCLC that continue to investigate novel ways to treat patients with this aggressive malignancy,” adds Dr. Scilla. 

For more information or to refer a patient for treatment, contact the UMGCCC referral office at 410-328-7904. 

References

Amgen. (2024, December 13). A phase 2 study of tarlatamab in patients with small cell lung cancer (SCLC) (DeLLphi-301). ClinicalTrials.gov.

Basumallik, N., & Agarwal, M. Small cell lung cancer. StatPearls

University of Maryland Medical System. (n.d.). Katherine A. Scilla, MD, FACP. Retrieved February 21, 2025.

University of Maryland Medical System. (n.d.). Samuel S. Rosner, MD. Retrieved February 21, 2025.

 

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