FDA Approves Reduced Monitoring Time for First 2 Doses of Tarlatamab in ES-SCLC

The FDA has approved a labeling update that reduces the post-infusion monitoring period to 6 to 8 hours following the first two doses of tarlatamab-dlle (Imdelltra) in patients with extensive-stage small cell lung cancer (ES-SCLC).¹

Previously, patients were required to be monitored for 22 to 24 hours in an appropriate health care setting after the first infusion, administered on cycle 1 day 1, and the second infusion, administered on cycle 1, day 8.

Under the updated label, it is recommended that patients are monitored for 6 to 8 hours after each of these first 2 infusions and undergo a follow-up assessment of vital signs the day after each dose. Patients are still advised to remain within 1 hour of an appropriate health care setting for a total of 48 hours after each of the first two infusions and to be accompanied by a caregiver during that window.

Monitoring recommendations for subsequent doses remain unchanged under the updated label. It is recommended that patients be monitored for 6 to 8 hours following the third dose (cycle 1, day 15) and following all doses in cycle 2, then 3 to 4 hours in cycles 3 and 4, and 2 hours for cycle 5 and any subsequent doses.

“People being treated for SCLC 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,” Jay Bradner, MD, executive vice president of research and development, AI, and data at Amgen, stated in the news release. "This approval is an important step in simplifying care for people living with and treating ES-SCLC. Reducing monitoring to 6 to 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."

What is the approved indication for tarlatamab?

In November 2025, the FDA granted full approval to tarlatamab for the treatment of adult patients with ES-SCLC with disease progression on or following platinum-based chemotherapy; this followed accelerated approval by the regulatory agency in the same inidcation in May 2024.^2-4

Accelerated approval was based on data from the phase 2 DeLLphi-301 trial (NCT05060016), and full approval was backed by confirmatory data from the phase 3 DeLLphi-304 trial (NCT05740566).³

What data supported the approval of tarlatamab?

DeLLphi-304 was an open-label, randomized study that evaluated tarlatamab against investigator’s choice of chemotherapy, including lurbinectedin (Zepzelca), topotecan, or amrubicin, in patients with ES-SCLC whose disease had progressed on or after 1 line of platinum-based chemotherapy.³

The primary end point was overall survival (OS).

Tarlatamab produced a median OS of 13.6 months (95% CI, 11.1-not evaluable) compared with 8.3 months (95% CI, 7.0-10.2) for chemotherapy (HR, 0.60; 95% CI, 0.47-0.77; P < .001), corresponding to a 40% reduction in the risk of death. The median progression-free survival was 4.2 months (95% CI, 3.0-4.4) with tarlatamab vs 3.2 months (95% CI, 2.9-4.2) with chemotherapy (HR, 0.72; 95% CI, 0.59-0.88; P < .001), and the overall response rate was 35% (95% CI, 29%-41%) vs 20% (95% CI, 16%-26%), respectively.

Tarlatamab is also under investigation in earlier lines of therapy. In the phase 3 DeLLphi-305 trial (NCT06211036), which is evaluating tarlatamab plus durvalumab (Imfinzi) vs durvalumab alone as first-line maintenance therapy in patients with ES-SCLC; the combination met its primary end point of OS at a planned interim analysis, according to Amgen.¹

What is the safety profile of tarlatamab?

In a pooled safety population of patients with ES-SCLC (n = 472), any-grade cytokine release syndrome (CRS) occurred in 57% of patients, including at grade 1 in 39%, grade 2 in 15%, grade 3 in 1.7%, and grade 4 in 0.2%.² The median time to onset of any-grade CRS was 16 hours (range, start of infusion to 15 days). Neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS), occurred in 65% of patients, with grade 3 or higher events reported in 7% of patients and fatal events in 0.2%; the incidence of signs and symptoms consistent with ICANS was 10%.

In DeLLphi-304, AEs led to discontinuation of tarlatamab in 6% of patients, although the only AE that led to permanent discontinuation in more than 1% of patients was pneumonia (1.2%). AEs led to dos interuptions in 38% of patients, with the most common including neutropenia (5%), fatigue (4.4%), pneumonia (4%), decreased appetite (2.8%), and COVID-19 (2%).

References

1. FDA approves reduced monitoring time for the first two doses of IMDELLTRA (tarlatamab-dlle). News release. Amgen. September 14, 2026. Accessed September 14, 2026. https://www.amgen.com/newsroom/press-releases/2026/09/fda-approves-reduced-monitoring-time-for-first-two-doses-of-imdelltra
2. Imdelltra (tarlatamab-dlle). Prescribing information. Amgen; 2026. Accessed September 14, 2026. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Imdelltra/imdelltra_fpi.pdf
3. FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer. FDA. November 19, 2025. Accessed September 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
4. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. FDA. May 16, 2024. Accessed September 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer