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

Small cell lung cancer (SCLC): At the door of targeted therapies. (PubMed, Biomol Biomed) - "For decades, outcomes stagnated: most patients present with extensive-stage disease, screening rarely detects early tumors, surgery is seldom feasible, and platinum-etoposide remained the first-line standard with median overall survival (OS) 80% of SCLC, enables T-cell-redirecting therapy: the bispecific T-cell engager tarlatamab improved OS to 13.6 vs 8.3 months over standard second-line chemotherapy, with manageable cytokine release syndrome and occasional ICANS. B7 homolog 3 (B7-H3, CD276), uniformly expressed across SCLC subtypes and linked to poor prognosis, is another compelling target: the antibody-drug conjugate ifinatamab deruxtecan achieved a 54.8% response rate and meaningful survival in heavily pretreated patients, earning FDA Breakthrough designation. Together, DLL3- and B7-H3-directed therapies (with additional ADCs against Trop-2 and SEZ6 in development) are redefining second-line and later care. Key next steps include optimizing..."

IO biomarker • Journal • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3 • SEZ6

BeOne Medicines Ltd…announced it has entered into an agreement to sell its royalty rights on the worldwide sales, excluding China, of Amgen’s IMDELLTRA (tarlatamab-dlle) for up to $950 million to Royalty Pharma. (Businesswire) - "Under the terms of the agreement, BeOne will receive an upfront payment of $885 million, with the option to sell remaining royalties within 12 months for up to $65 million. BeOne will share in a portion of the royalty on annual sales above $1.5 billion, and will maintain royalty and all other rights to other assets under the terms of the existing collaboration with Amgen, including xaluritamig, a first-in-class STEAP1 x CD3 XmAb currently being studied in patients with metastatic castration-resistant prostate cancer (mCRPC)."

Commercial • Castration-Resistant Prostate Cancer • Small Cell Lung Cancer

Early pseudo-progression of brain metastases following tarlatamab therapy in relapsed small cell lung cancer. (PubMed, Lung Cancer) - No abstract available

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

Tarlatamab Efficacy and Safety in Chinese Patients with Advanced Small Cell Lung Cancer: Phase 2 DeLLphi-307 (IASLC-WCLC 2025) - "There were no new or unexpected safety concerns. This encouraging region-specific clinical evidence supports tarlatamab's potential as a new treatment option for Chinese patients with previously treated extensive-stage SCLC."

Clinical • Metastases • P2 data • Heart Failure • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

DeLLphi-309: A Phase 2, Open-label, Randomized, Multicenter Study of Tarlatamab Dosing Regimens in Subjects With SCLC (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Amgen | Trial completion date: May 2029 ➔ Dec 2028 | Trial primary completion date: May 2029 ➔ Dec 2028

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

Safety and Survival Update of Tarlatamab with Anti-PD-L1 as 1L Maintenance After Chemo-IO for ES-SCLC: DeLLphi-303 Ph1b Trial (IASLC-WCLC 2025) - P1, P3 | "Abstract is embargoed at this time."

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

TARLATAMAB: A NEWLY APPROVED TREATMENT FOR EXTENSIVE-STAGE SMALL CELL LUNG CANCER AND ITS ASSOCIATION WITH CYTOKINE RELEASE SYNDROME (CHEST 2025) - No abstract available

Cytokine release syndrome • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study (ESMO 2025) - No abstract available

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

RABBIT: Radiation Combined With BIspecific T-Cell Engager in DLL3 Expressing Tumors (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: University of Arizona | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Brain Cancer • Cervical Cancer • Endocrine Cancer • Genito-urinary Cancer • Glioblastoma • Large Cell Carcinoma • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Testicular Cancer • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma

Multi-Institution Analysis Evaluating Safety, Efficacy and ctDNA Dynamics Following Tarlatamab in ES-SCLC and LCNEC Patients (IASLC-WCLC 2025) - "CRS was observed in 56% of patients, all grade 1/2 in severity, with median onset within 24 hours following C1D1 and 44% requiring tocilizumab. However, in this non-trial setting, rates and timing of CRS/ICANS differed from previous reports, highlighting the need for careful observation and care coordination as this therapy is utilized in real-world practice. Novel biomarkers of response and resistance are needed in this setting, with longitudinal ctDNA dynamics showing potential promise, though larger, prospective studies are needed."

Circulating tumor DNA • Clinical • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Small Cell Lung Cancer • Solid Tumor • DLL3

HER2- and TROP2-Directed Antibody Drug Conjugates Show Potent Antitumor Activities in Small Cell Lung Cancer (IASLC-WCLC 2025) - "Efficacy of trastuzumab deruxtecan (HER2-ADC), trastuzumab, sacituzumab govitecan (TROP2-ADC), sacituzumab and the TOP1 inhibitor payloads (deruxtecan and SN-38) were evaluated in SCLC preclinical models. TROP2-ADC similarly demonstrated significant antitumor activity. Conclusions : These findings demonstrate that targeting cell surface HER2 and TROP2 using ADCs is effective in SCLC, including the SCLC-P subtype, which typically is resistant to standard of care therapies and likely to tarlatamab, due to low DLL3 expression."

Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3 • HER-2 • SEZ6 • SLFN11 • TACSTD2 • TOP1

BeOne Medicines Announces Second Quarter 2025 Financial Results and Business Updates (Businesswire) - "BGB-16673 (BTK CDAC): Achieved first subject enrolled for global Phase 3 BGB-16673-302 trial for the treatment of R/R CLL. Achieved first subject enrolled for China Phase 3 BGB-16673-303 trial for the treatment of R/R/ CLL. Initiated enrollment of potentially registration enabling Phase 2 trial for the treatment of R/R WM. Tarlatamab (AMG 757): Achieved acceptance of BLA and priority review in China for the treatment of 3L+ small cell lung cancer (SCLC). Achieved acceptance of BLA in China for the treatment of 2L SCLC."

China filing • Priority review • Trial status • Chronic Lymphocytic Leukemia • Small Cell Lung Cancer • Waldenstrom Macroglobulinemia

Preliminary Efficacy and Toxicity of Tarlatamab in Patients with Medullary Thyroid Carcinoma (ATA 2025) - No abstract available

Clinical • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma

A Single-Center Experience With Tarlatamab in Relapsed/Refractory Advanced Small Cell Lung Cancer and Neuroendocrine Carcinomas (IASLC-WCLC 2025) - "CNS progression remained common, including CNS-only events. Further studies such as DLL3 expression characterization and molecular analyses of patient samples will be essential to determine predictors of response and risk factors for severe adverse events to tarlatamab."

Clinical • IO biomarker • Metastases • Endocrine Cancer • Interstitial Lung Disease • Large Cell Carcinoma • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • DLL3

Patient-reported outcomes (PROs) from DeLLphi-304: the first phase 3 trial evaluating tarlatamab and chemotherapy (CTx) in patients (Pts) with previously treated small cell lung cancer (SCLC) (ESMO 2025) - No abstract available

Clinical • P3 data • Patient reported outcomes • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Neurologic Adverse Events Associated With T-cell Engager Therapy in Multiple Myeloma: A Pharmacovigilance Study. (PubMed, Cureus) - "T-cell engager (TCE) therapies, such as teclistamab (TL), talquetamab (TQ), and elranatamab (ER), have emerged as promising options...Conclusion NAEs are a substantial part of the toxicity profile of TCEs in RRMM, particularly in the context of TL. These findings underscore the need for proactive neurologic monitoring and further research to identify predictive markers and improve management strategies."

Adverse events • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Real-World Multi-Institution Analysis of Patients With Small Cell Lung Cancer Treated With Tarlatamab (IASLC-WCLC 2025) - "These patients had comparable CRS rates but higher rates of ICANS, lower objective response rate, and more frequent primary progression. Detailed analyses are warranted to understand patient and disease characteristics predictive of toxicity and response to optimize patient selection."

Clinical • Real-world • Real-world evidence • Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • DLL3

Efficacy Outcomes Between Tarlatamab and Real-World Physicians' Choice of Therapies for Previously Treated Extensive Stage Small Cell Lung Cancer. (PubMed, Oncologist) - "The study findings suggest that tarlatamab offers potential clinical benefits relative to comparator treatments. This analysis underscores the potential of tarlatamab to become a new therapeutic option for previously treated SCLC, a disease that has historically been associated with extremely poor outcomes and limited treatment options."

Journal • Real-world evidence • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

DeLLphi-312: A Study Comparing Tarlatamab, Durvalumab, Carboplatin, and Etoposide Versus Durvalumab, Carboplatin, and Etoposide in First-line Extensive Stage Small-Cell Lung Cancer (ES-SCLC) (clinicaltrials.gov) - P3 | N=330 | Recruiting | Sponsor: Amgen | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Early Pseudoprogression After Tarlatamab in Small-Cell Lung Cancer: A Case Report. (PubMed, Respirol Case Rep) - "By Day 13, computed tomography demonstrated regression of thoracic and hepatic lesions and falling pro-gastrin-releasing peptide (pro-GRP). Early pseudoprogression and paraneoplastic biomarker improvement may predict efficacy."

Journal • Hepatology • Lung Cancer • Musculoskeletal Pain • Oncology • Pain • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • GRP-10

Surface Targeting Strategies to Overcome Heterogeneity Associated With Treatment Resistance in Small Cell Lung Cancer (SCLC) (IASLC-WCLC 2025) - "The recent FDA approval of tarlatamab, a DLL3 targeting bispecific T-cell engager (BiTE), alongside unprecedented response rates observed with multiple antibody-drug conjugates (ADCs), have ushered in a paradigm shift towards surface targeting strategies in relapsed SCLC patients... Single-agent surface targeting strategies are effective in preclinical models, including those resistant to other common SCLC therapies (i.e., platinum chemotherapy). Notably, single-cell transcriptional profiling of relapsed SCLC patient biopsies revealed mutually exclusive expression of surface genes in distinct cell populations (i.e., DLL3/SEZ6 vs. TROP2/HER2/B7-H3), including senescent, drug tolerant persister cells (DTPCs), representing a unique opportunity to target heterogeneous populations."

Heterogeneity • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3 • HER-2 • SEZ6 • TOP1

Multi-Institutional Real-World Experience of Early Tarlatamab-Related Toxicities for Extensive Stage Small Cell Lung Cancer (IASLC-WCLC 2025) - "No tocilizumab was required. This is the largest case series of Hispanic patients treated with tarlatamab. Future studies should refine toxicity mitigation protocols to enhance the safety and tolerability of tarlatamab in broader patient populations."

Clinical • Real-world • Real-world evidence • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

AMGEN REPORTS SECOND QUARTER 2025 FINANCIAL RESULTS (Amgen Press Release) - "XGEVA (denosumab) sales decreased 5% year-over-year to $532 million in the second quarter, driven by 2% unfavorable changes to estimated sales deductions and volume decline. For 2025, we expect sales erosion driven by biosimilar competition in the second half of the year, as biosimilars have now launched in the U.S. market. Nplate (romiplostim) sales increased 7% year-over-year to $369 million in the second quarter, driven by volume growth. IMDELLTRA (tarlatamab-dlle)/IMDYLLTRA (tarlatamab) generated $134 million of sales in the second quarter. Sales increased 65% quarter-over-quarter, driven by volume growth. MVASI (bevacizumab-awwb) sales increased 22% year-over-year to $191 million in the second quarter, driven by 16% favorable changes to estimated sales deductions, 6% volume growth and 5% higher net selling price, partially offset by lower inventory levels."

Sales • Aplastic Anemia • Breast Cancer • Cervical Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Ovarian Cancer • Prostate Cancer • Renal Cell Carcinoma • Thrombocytopenic Purpura

A Study of Tarlatamab for People With Prostate Cancer (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Tracking Ctc Phenotypes in SCLC Liquid Biopsies as a Diagnostic and Therapy Response Assessment Tool (IASLC-WCLC 2025) - "Computational analysis was performed to assess intra- and inter- patient CTC heterogeneity, phenotypic differences between treatment-naïve and standard-of-care and Tarlatamab treated patients, and CTC dynamic changes in longitudinal specimens...Longitudinal tracking of CTCs in a subset of patients revealed subtype switching, specifically a gradual decline in NeuroD1 alongside an increase of POU2F3 levels. Conclusions : Our approach can serve as a potential diagnostic and therapy response assessment tool where by utilizing CyTOF to longitudinally track CTCs directly in SCLC patient liquid biopsies can lead to tailoring SCLC therapy at a personalized level."

Biopsy • IO biomarker • Liquid biopsy • Lung Cancer • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • ASCL1 • CD24 • CTCs • DLL3 • EPCAM • MUC1 • NCAM1 • NEUROD1 • NKX2-1 • POU2F3 • PTPRC