IMDELLTRA (tarlatamab-dlle) is a bispecific T-cell engager that binds DLL3, a protein expressed in up to 96% of SCLC tumors but largely absent in healthy tissue, and CD3 on T-cells, enabling selective tumor cell targeting. This high tumor selectivity has contributed to improved tolerability compared to chemotherapy.

According to new interim results from the global Phase III DeLLphi-304 trial, Amgen’s DLL3-targeting T-cell engager IMDELLTRA has demonstrated a 40% reduction in the risk of death compared to standard chemotherapy in relapsed SCLC. 

With 509 patients who progressed after at least one line of platinum-based chemotherapy, IMDELLTRA extended median Overall Survival to 13.6 months versus 8.3 months with regional standard-of-care treatments, including HYCAMTIN (topotecan), ZEPZELCA (lurbinectedin), and CALSED (amrubicin). The secondary endpoint of Progression-free Survival (PFS) also showed statistically significant improvement, with a median PFS of 4.2 months for IMDELLTRA versus 3.7 months for chemotherapy, reflecting a 29% relative gain.

The safety profile for IMDELLTRA in DeLLphi-304 was consistent with its known profile. In DeLLphi-304, lower rates of Grade 3 or higher Treatment-related Adverse Events (TRAEs) occurred with IMDELLTRA versus the control arm, and discontinuations due to TRAEs were lower with IMDELLTRA compared to the control arm. The most common Grade 3 or greater TRAEs were neutropenia and lymphopenia with IMDELLTRA and anemia and neutropenia with local SOC chemotherapy. 

IMDELLTRA carries a boxed warning for CRS and neurologic toxicities, consistent with its known safety profile. Patient-reported outcomes also significantly favored IMDELLTRA, underscoring its clinical benefit not only in efficacy but also in quality of life.

KOL insights

“The data from DeLLphi-304 mark a major milestone for people with relapsed small cell lung cancer. Tarlatamab is associated with significant improvements in both overall and progression-free survival over standard chemotherapy in patients with recurrent or progressive disease. This study also provides confirmatory data on management of potential toxicities associated with bispecific T-cell engager therapies in a large patient cohort, which is crucial to continuing to improve the experience of patients treated with these medicines.” – Expert Opinion

“There was already a lot of enthusiasm about tarlatamab for previously treated extensive-stage SCLC, given the potential for durable response, and these data are likely to increase its adoption for this patient population.”– Expert Opinion

Conclusion

SCLC, which represents nearly 15% of all lung cancers, accounted for approximately 33,000 incident cases in the US. In May 2024, the US FDA granted accelerated approval to IMDELLTRA as the first—and currently only—targeted bispecific T-cell engager for patients with extensive-stage SCLC whose disease progressed after platinum-based chemotherapy.

Further evaluation of IMDELLTRA in the second-line treatment led to statistically significant and clinically meaningful improvements in PFS and OS compared with chemotherapy in patients with SCLC. DeLLphi-304 met its primary OS endpoint and key secondary PFS endpoint. 

The launch of IMDELLTRA, the first DLL3-targeted therapy, has garnered widespread attention and marked a major milestone in DLL3-directed treatment, generating around USD 115 million in revenue in 2024 in the US. This DLL3-targeting therapy in ES-SCLC comprises a transformative option demonstrating long-lasting responses in pretreated patients. This approval further demonstrates our commitment to addressing aggressive cancers through our second FDA-approved BiTE molecule. IMDELLTRA offers these patients who are in urgent need of new innovative therapies hope, and we're proud to deliver this long-awaited effective treatment to them.