FDA Approves Reduced Monitoring Time for First 2 Tarlatamab Doses

The FDA has approved an update to the prescribing information for tarlatamab-dlle (Imdelltra), a bispecific T-cell engager targeting DLL3 and CD3, substantially reducing the postinfusion monitoring period required after the first 2 doses in patients with extensive-stage small cell lung cancer (ES-SCLC).¹ The change is intended to ease a key practical barrier to administering the agent outside major treatment centers.¹

Under the previous label, patients required 22 to 24 hours of monitoring in a health care setting following each of the first 2 tarlatamab infusions. The updated label now requires 6 to 8 hours of monitoring from the start of infusion, plus a follow-up assessment, including vital signs, the day after each of those first 2 doses. Patients must still remain within 1 hour of an appropriate health care setting for a total of 48 hours from the start of each infusion and must be accompanied by a caregiver.

Indication and Safety Profile Unaffected

The approved indication for tarlatamab—treatment of ES-SCLC with disease progression on or after platinum-based chemotherapy—is unchanged, as is its dosing regimen. The product's boxed warnings for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS), also remain in place. In a pooled safety analysis across the DeLLphi-300 (NCT03319940), DeLLphi-301 (NCT05060016), and DeLLphi-304 (NCT05740566) trials comprising 473 patients with small cell lung cancer, CRS occurred in 57% of patients (39% grade 1, 15% grade 2, 1.7% grade 3, 0.2% grade 4), and neurologic toxicity/ICANS occurred in 65% of patients, with grade 3 or higher events in 7%.

Other notable adverse events included cytopenias—neutropenia (16%, including 9% grade 3/4), thrombocytopenia (30%, including 2.2% grade 3/4), and anemia (56%, including 4.7% grade 3/4)—as well as infections in 43% of patients (14% grade 3/4), including pneumonia (11%), urinary tract infection (9%), and COVID-19 (6%). Hepatotoxicity included elevated alanine transaminase (39%, including 2.5% grade 3/4) and elevated aspartate aminotransferase (43%, including 3.2% grade 3/4). The most common adverse reactions occurring in at least 20% of patients were CRS, fatigue (48%), decreased appetite (38%), dysgeusia (34%), pyrexia (33%), constipation (31%), musculoskeletal pain (31%), and nausea (25%).

Clinical Rationale for the Change

SCLC accounts for approximately 13% to 15% of the more than 2.6 million lung cancer cases diagnosed globally each year, and an estimated 80% to 85% of patients with cancer in the US receive care in community oncology settings rather than academic centers. Amgen, the sponsor, has positioned the monitoring reduction as a way to make tarlatamab more practical to administer outside large referral centers.

Jay Bradner, MD, executive vice president, Research and Development, Artificial Intelligence and Data, at Amgen, said in a news release, “People being treated for small cell lung cancer are already navigating an aggressive and difficult-to-treat disease, and the time required to receive and monitor treatment can add to that burden for both patients and care centers. This approval is an important step in simplifying care for people living with and treating ES-SCLC. Reducing monitoring to 6-8 hours for the initial doses may help address practical barriers associated with administering [tarlatamab] and enable more patients to receive care closer to home. We continue to work closely with the healthcare community to ensure appropriate educational support for navigating [tarlatamab] treatment is available to providers, patients and care partners.”

David M. Waterhouse, MD, MPH, FASCO, a medical oncologist/hematologist at Oncology Hematology Care in Cincinnati, Ohio, said in a news release, “In community oncology, we care for patients where they live, and for people living with small cell lung cancer, that matters. These patients are often very sick, and traveling long distances or spending extended time in a healthcare setting can be difficult for them and their families. Reducing the required monitoring period may make [tarlatamab] more feasible to administer in community practices, helping more patients receive treatment in their local care network and spend less time away from their support systems.”

Regulatory and Clinical Development History

Tarlatamab first received accelerated approval from the FDA in May 2024 for ES-SCLC with disease progression on or after platinum-based chemotherapy.² That approval converted to full approval in November 2025 based on results from the phase 3 DeLLphi-304 trial (NCT05740566), in which tarlatamab reduced the risk of death by 40% and extended median overall survival by more than 5 months compared with standard-of-care chemotherapy in previously treated ES-SCLC.

REFERENCES

1. FDA approves reduced monitoring time for first two doses of IMDELLTRA. News release. Amgen. September 14, 2026. Accessed September 14, 2026. https://tinyurl.com/5ykt7jdw

2. FDA grants traditional approval to tarlatamab-dlle for extensive-stage small cell lung cancer. FDA. Updated November 19, 2025. Accessed September 14, 2026. https://tinyurl.com/52rezss5