Imdelltra (tarlatamab-dlle)

P3, N=430, Not yet recruiting, PrECOG, LLC.

From approval of immune checkpoint inhibitors and lurbinectedin, a newer chemotherapy agent, to novel immunotherapies such as tarlatamab, a DLL3-CD3 bispecific T-cell engager, and other upcoming promising drugs, the therapeutic armamentarium for SCLC is steadily expanding. In this study, we review the current landscape of both systemic therapy as well as radiation therapy for SCLC, with a focus on major developments over the past decade, current standards of care, and novel therapeutics that are expected to revolutionize the treatment of this aggressive malignancy.

For EGFR-mutant NSCLC, sequential development of tyrosine kinase inhibitors (TKIs) from first- to third-generation agents-culminating in osimertinib-has markedly improved survival. Similarly, successive generations of ALK inhibitors, including alectinib, brigatinib, and lorlatinib, have extended disease control, particularly within the central nervous system. The introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan for HER2-mutant NSCLC, and emerging TKIs like zongertinib, represent new therapeutic milestones...Beyond lung cancer, our group, in collaboration with Juntendo University ARO (academic research organization) and fifteen institutions in Japan, conducted the MARBLE phase II trial of atezolizumab plus chemotherapy for thymic carcinoma, achieving a 56% objective response rate and 9.6-month median progression-free survival, supporting potential ICI approval in Japan...The DLL3-targeted BiTE tarlatamab significantly improved overall survival to 13.6 months in the phase III DeLLphi-304 trial for relapsed SCLC, with manageable cytokine release syndrome. Collectively, these advances signify a shift toward biologically driven, molecular-targeted or immune-integrated therapy, aiming to transform lung cancer into a chronic, manageable disease in the future, hopefully.

P1, N=845, Recruiting, GlaxoSmithKline | N=590 --> 845 | Trial completion date: May 2027 --> Jun 2029 | Trial primary completion date: Sep 2026 --> Oct 2028

P1, N=29, Active, not recruiting, Amgen | N=200 --> 29

High baseline disease burden may predispose subjects to more severe CRS without necessitating treatment discontinuation. Early reimaging in these situations may reveal marked treatment response and inform clinical decision-making.

While immunotherapy has improved outcomes, most patients ultimately relapse. Integrating molecular subtyping, optimizing multimodality care, and accelerating clinical trial enrollment are key to further progress in SCLC.

A modified dosing and monitoring protocol may improve the safety of tarlatamab in patients with MTC while maintaining efficacy. Further research is needed to evaluate the role of tarlatamab in MTC.

Affordability constraints are more stringent in China than in the United States. These findings inform value-based pricing, reimbursement negotiations, and equitable access strategies.

P2, N=87, Recruiting, Grupo Espanol de Tumores Neuroendocrinos

Emerging therapies, such as antibody-drug conjugates targeting B7-H3/DLL3 (I-Dxd, ZL-1310) and bispecific antibody tarlatamab, have demonstrated intracranial response rates of 62.5%-71%. Future directions involve developing new drugs with high blood-brain barrier penetration, such as radioligand therapy, conducting prospective studies to optimize HA and SRS applications, establishing high-quality RWE databases to support personalized treatments, exploring molecular subtypes (SCLC-A/N/P/I) and leveraging AI technologies to advance precision radiotherapy. SCLC management needs to be patient-centered, integrating precise treatment of brain metastases, QoL improvement, and the application of RWE to achieve a balance between survival benefits and QoL.

P1, N=160, Recruiting, Amgen | Not yet recruiting --> Recruiting