Imdelltra (tarlatamab-dlle) / Amgen, BeOne Medicines, Royalty - LARVOL DELTA

Real-world efficacy and safety of tarlatamab in previously treated small cell lung cancer in Korea (ESMO Asia 2025) - "Tarlatamab demonstrated encouraging antitumor activity and a manageable safety profile in heavily pretreated Korean SCLC patients. CRS was common but mild, whereas ICANS was rare. An elevated NLR may predict the risk of CRS."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Tarlatamab efficacy in relapsed small cell lung cancer correlates with response and progression patterns and tumor marker kinetics (ESMO Asia 2025) - "Tarlatamab showed promising effectiveness for relapsed SCLC. Baseline serum NSE and ProGRP levels may serve as predictive markers for treatment response and disease progression. Regarding the response and progression patterns, the frequency of MR and multi-site progression suggests heterogeneous tumor biology, supporting further investigation through clonal analysis to inform personalized treatment strategies."

Clinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3 • GRP-10

Reassessing Clinical Trial Eligibility: Real-world Impact of Bispecific Antibody Exclusion Criteria (SITC 2025) - "We analyzed how current trial criteria may restrict access and assessed clinical outcomes of patients treated with bsAbs outside of clinical trial settings.Methods We reviewed actively recruiting phase 2 and 3 clinical trials involving bsAbs listed on the National Cancer Institute's website (www.cancer.gov) for the following agents: blinatumomab, tarlatamab, epcoritamab, glofitamab, mosunetuzumab, talquetamab, teclistamab, and elranatamab. Bispecifics and number of patients excluded based on clinical trial criteria describedAbstract 979 Figure 1Request permissionsTreatment duration by eligibility status. Bispecific treatment duration by clinical trial eligibility status"

Clinical • Real-world • Real-world evidence • Oncology • Solid Tumor

Bispecific immunotherapy based on antibodies, T-cell receptors, and aptamers: mechanisms of action, adverse effects, and future perspectives. (PubMed, Front Immunol) - "IgG formats-including blinatumomab, teclistamab, mosunetuzumab, and tarlatamab-achieve high objective-response rates in hematologic malignancies and are increasingly demonstrating clinical activity in solid tumors. TCR-based constructs broaden the repertoire of actionable targets by recognizing intracellular antigens presented on MHC molecules, as exemplified by the approval of tebentafusp for uveal melanoma...The integrated evidence indicates that continued progress in bispecific immunotherapy will depend on the incorporation of predictive molecular biomarkers, dynamic monitoring of the evolving antigenic landscape, and the standardization of biomanufacturing processes. These advances are expected to accelerate the clinical deployment of next-generation, multipurpose bispecific constructs."

Adverse events • IO biomarker • Journal • Review • Eye Cancer • Fibrosis • Hematological Disorders • Hematological Malignancies • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

A multi-institutional perspective on tarlatamab administration and management of CRS/ICANS. (PubMed, Lung Cancer) - "This perspective highlights current best practices and suggests future directions to improve on our current approaches for tarlatamab administration and CRS/ICANS management."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Durable Complete Response of a Delta-Like Ligand 3 Expressing Head and Neck Neuroendocrine Carcinoma to Tarlatamab. (PubMed, JCO Precis Oncol) - No abstract available

Journal • Endocrine Cancer • Neuroendocrine Carcinoma • Oncology • Solid Tumor

Rapid-onset Severe Cytokine Release Syndrome With Marked Interleukin-6 Increase and Acute Liver Injury After the First Tarlatamab Dose in SCLC: Case Report. (PubMed, JTO Clin Res Rep) - "Severe CRS and liver injury rapidly developed in the patient after the first tarlatamab dose, which led to treatment discontinuation. This report also presents the temporal changes in serum interleukin-6 levels, highlighting its potential utility as a biomarker for the onset and severity of CRS."

Journal • Hepatology • Inflammation • Liver Failure • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • IL6

Response to letter Re: Tarlatamab-induced immune-related adverse events: Real-world pharmacovigilance study using the FAERS database. (PubMed, Eur J Cancer) - No abstract available

Adverse events • Journal • Real-world evidence

Letter Re: Tarlatamab-induced immune-related adverse events: Real-world pharmacovigilance study using the FAERS database. (PubMed, Eur J Cancer) - No abstract available

Adverse events • Journal • Real-world evidence

Early Pseudoprogression Mimicking Pneumonitis After Tarlatamab Therapy: A Case Suggestive of Immune Cell-Associated Respiratory Syndrome (ICARS). (PubMed, Respirol Case Rep) - "High-dose methylprednisolone and tocilizumab produced prompt clinical and radiographic improvement; follow-up imaging showed resolution of infiltrates and tumour regression below baseline, consistent with pseudoprogression. We speculate that baseline carcinomatous lymphangitis may predispose to ICARS. Recognising ICARS may prevent misdiagnosis and avoid premature discontinuation of effective therapy."

Journal • Inflammation • Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • DLL3

Efficacy Outcomes and Risk Factors for CRS and ICANS with Tarlatamab in Small Cell Lung Cancer: Insights from Clinical Practice (ESMO-IO 2025) - "Intracranial activity of tarlatamab was noted without prior radiation providing a radiation sparing approach. Tarlatamab showed efficacy and tolerability across multiple undescribed populations from clinical trials.Legal entity responsible for the study The authors."

Clinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Unlock tarlatamab: A phase II, multicenter, open-label, study investigating tarlatamab in patients with metastatic/locally advanced small cell lung cancer and other poorly differentiated neuroendocrine carcinomas with integrated biomarker analyses (ESMO-IO 2025) - P2 | "Analyses include DLL3 expression dynamics, genomic and transcriptomic profiling, epigenetic characterization, tumor microenvironment mapping, ctDNA kinetics, and establishment of patient-derived xenografts. This study aims to uncover mechanisms driving response and resistance to tarlatamab, ultimately informing next-generation therapeutic strategies.Clinical trial identification NCT07016230.Legal entity responsible for the study Gustave Roussy."

Biomarker • Clinical • Metastases • P2 data • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

DLL3 Expression by Immunohistochemistry in Rare Neuroendocrine Neoplasms and Associated Response to Off Label Tarlatamab (ESMO-IO 2025) - "Tarlatamab was well tolerated with only one case (7.7%) of grade 3 or higher cytokine release syndrome or immune effector cell associated neurotoxicity syndrome.Conclusions Tarlatamab demonstrated promising activity in DLL3-expressing rare NENs, supporting its use as a precision medicine strategy in patients with rare NENs other than small cell lung cancer. Prospective studies and standardized DLL3 testing are warranted across all tumor types.Legal entity responsible for the study The authors."

Bladder Cancer • Endocrine Cancer • Esophageal Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

A phase II study evaluating the safety, efficacy, and intracranial activity of tarlatamab in recurrent/refractory IDH-mutant gliomas (TARGID) (SNO 2025) - "The trial is currently in activation, with first patient enrollment anticipated in Q3 2025. The study is supported by the provision of study drug from Amgen as an investigator-initiated trial."

Clinical • P2 data • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Solid Tumor • CD8 • DLL3 • IDH1 • IDH2

Rapid disease progression and hydrocephalus following tarlatamab therapy initiation: A case report. (PubMed, Respir Med Case Rep) - "This case highlights the need to consider the possibility of rapid disease progression following tarlatamab administration and underscores the importance of adequate assessment to exclude ICANS. Since rapid tumor progression may lead to a decline in the patient's general condition, careful follow-up is advised."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Ventriculomegaly

TARLATEM: Combination of Tarlatamab and Temozolomide in Patients With Central Nervous System Tumors (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: Centre Leon Berard

New P1/2 trial • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Brief Report: Multi-institution real-world analysis evaluating safety, efficacy and ctDNA dynamics following tarlatamab in patients with previously treated SCLC and LCNEC (JTO Clinical and Research Reports) - "Rates of CRS and ICANS were 54% and 33%, respectively, with the majority being grade 1-2 in severity (100% and 87.5%). Of the 30 patients included in our efficacy analysis, the best overall response rate (BOR) was 67% and disease control rate (DCR) was 73%. With median follow up of 5.7 months, median PFS was 4.9 months (95% CI: 4-NR) and median OS was not reached (95% CI: 4.8-NR)."

Retrospective data • Large Cell Neuroendocrine Carcinoma • Small Cell Lung Cancer

MERLIN: Study of Tarlatamab as Maintenance Treatment After Chemo-radiotherapy for Limited Stage SCLC Patients (clinicaltrials.gov) - P2 | N=37 | Not yet recruiting | Sponsor: Fundación GECP

New P2 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

Early trajectory of inflammatory cytokines following tarlatamab administration in three advanced SCLC patients. (PubMed, Cancer Immunol Immunother) - "This cytokine profiling highlights the complex pathophysiology of CRS and the involvement of diverse cytokine networks beyond the IL-6 axis. These findings may guide future biomarker development, disease classification, and therapeutic strategies beyond IL-6 inhibition, advancing personalized CRS management."

Journal • Developmental Disorders • Inflammation • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • HGF • IFNA1 • IFNG • IL10 • IL1R1

Tarlatamab population survival kinetics in extensive-stage small cell lung cancer: brief report. (PubMed, Lung Cancer) - "In ES-SCLC, EDNLRA of tarlatamab PFS curves and log-linear plots of response duration curves suggest two distinct subpopulations- one deriving marked benefit from tarlatamab and the other deriving much less benefit. Individual patient data might provide insight into underlying driving factors."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

DeLLphi-300: Study Evaluating Safety, Tolerability and Pharmacokinetics (PK) of Tarlatamab in Adults With Small Cell Lung Cancer (SCLC) (clinicaltrials.gov) - P1 | N=269 | Active, not recruiting | Sponsor: Amgen | Trial completion date: Oct 2026 ➔ Dec 2027 | Trial primary completion date: Oct 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

DLL3 Immunohistochemical Expression in Neuroendocrine-Transformed EGFR-Mutant Lung Cancer and Two Cases of Tarlatamab Therapy. (PubMed, JTO Clin Res Rep) - "Tarlatamab appeared effective when added to osimertinib. Further analysis of the combination of bispecific DLL3 T-cell engager and EGFR tyrosine kinase inhibitor is warranted to confirm these findings."

Journal • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3 • EGFR • RB1 • TP53

FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer (FDA) - "Efficacy was evaluated in DeLLphi-304 (NCT05740566), a multicenter, randomized, open-label trial in patients with SCLC with disease progression following treatment with platinum-based chemotherapy with or without an anti-PD-(L)1 antibody....The recommended tarlatamab-dlle dose is 1 mg on Cycle 1, Day 1 followed by 10 mg on Days 8, 15, and every two weeks thereafter until disease progression or unacceptable toxicity."

FDA approval • Small Cell Lung Cancer

A phase II study evaluating the safety, efficacy, and intracranial activity of tarlatamab in recurrent/refractory IDH-mutant gliomas (TARGID) (WFNOS 2025) - "The trial is currently in activation, with first patient enrollment anticipated in Q3 2025. The study is supported by the provision of study drug from Amgen as an investigator-initiated trial."

Clinical • P2 data • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • CD8 • DLL3 • IDH1 • IDH2

Two Cases of Electron Microscopy-proven SMARCA4 Deficient Undifferentiated Large Cell Neuroendocrine Carcinoma Presenting as Subcutaneous Masses (ASDP 2025) - "Both patients were treated with atezolizumab, carboplatin, and etoposide...The female patient showed no response to this regimen and was subsequently treated with tarlatamab-dlle, also without response, with ongoing disease progression...Electron microscopy provides ultrastructural evidence which provides greater diagnostic certainty. A high index of suspicion and the use of appropriate techniques, including electron microscopy, may be necessary to establish a definitive diagnosis in challenging cases."

Clinical • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor • NCAM1 • NKX2-1 • SMARCA4 • SYP