Small-cell lung cancer (SCLC) accounts for ~15% of all lung cancer cases and is known for its high fatality rate. About two-thirds of SCLC patients are diagnosed with cancer that has already spread beyond the lungs, and the average survival time for those with advanced-stage disease is just a little over one year. While the introduction of PD-L1 inhibitors as a part of the initial treatment for SCLC patients marked significant progress, the limited improvement in survival underscores the pressing requirement for new approaches to enhance the treatment of this condition. With very limited treatment options available for patients suffering from SCLC, bispecific T-cell engager (BiTE) seems to be a potential target for treatment development. 

Several DLL3-targeted agents are being investigated in the clinical studies and Tarlatamab is one of them. The drug is a bispecific T-cell engager (BiTE), representing a new immunotherapeutic approach for SCLC. It binds to both delta-like ligand 3 (DLL3) on SCLC cells and CD3 on T cells, resulting in T-cell mediated tumor lysis. 

A Phase I study demonstrated encouraging safety and efficacy, median duration of response (mDoR): 12.3 months; median overall survival (mOS): 13.2 months in previously treated SCLC. In the Phase II trial the drug demonstrated impressive antitumor activity with durable responses and promising survival. The potentially registrational DeLLphi-301 was designed to evaluate tarlatamab in SCLC patients who had failed two or more prior lines of treatment. 

The most common treatment-emergent adverse events was cytokine release syndrome, primarily occurring in cycle 1, and was mostly grade 1 or 2. Incidence of grade 3 CRS and grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurologic events was low, with no grade 4 or 5 events. Discontinuations due to treatment-related AEs were infrequent. Similar safety profiles were seen with 24h or 48h inpatient monitoring.

KOL insights

“Lack of control arm was a limitation of DeLLphi-301 & note that the DeLLphi-304 trial of tarlatamab vs standard of care is ongoing. Interested to see if $AMGN can get approval based on DeLLphi-301” –MD, US

Conclusion

Tarlatamab seems to be a potential therapy for the patients with previously treated SCLC. Several DLL3-targeted therapies, such as Rova-T, showed promise in small-cell lung cancer (SCLC) but had limitations. A newer option, BI 764532, is showing positive results in preclinical models and is in a Phase I study for SCLC patients. Another approach, HPN328, with a trispecific design, is also in a Phase I/IIa study for SCLC and has shown early signs of effectiveness without severe side effects. These therapies aim to improve treatment options for SCLC. Considering both preclinical and clinical data, it becomes evident that DLL3 is an exciting and promising target for treating individuals with SCLC. The early safety and effectiveness results of tarlatamab represent a significant achievement, confirming the potential of DLL3 as a target and MHC-I bypass as an immunotherapy approach for SCLC.

SCLC accounts for up to 15% of lung cancer. DelveInsight estimates that the total incident population of SCLC in the US will reach ~40,000 in 2032. If approved, tarlatamab can compete with checkpoint inhibitors and grab a significant market share.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Small Cell Lung Cancer (SCLC) Market Forecast Report

Note: The therapeutics segment is experiencing significant NSCLC clinical trial activity, which is further expected to drive Non-Small Cell Lung Caner market growth in the coming years.