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

Establishing T Cell–Engaging Bispecific Antibody Therapy in Community Practice (SOHO 2026) - "Introduction: T cell–engaging bispecific antibodies (TCEs) are increasingly used for relapsed or refractory malignancies, but implementation outside academic centers remains challenging because of step-up dosing requirements, cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), supportive care needs, infections, and the requirement for immediate access to tocilizumab...Therapies included tarlatamab (n = 13), talquetamab (n = 6), teclistamab (n = 2), glofitamab (n = 3), and mosunetuzumab (n = 1)... A structured multidisciplinary care model (navigator, coordinator, infusion nurse, pharmacist, advanced nurse practitioner, hospitalist) incorporating standardized protocols, caregiver engagement, and rapid physician access enables safe, effective delivery and broader adoption of TCEs in the community."

Bispecific • Oncology

RAGNAR: Refractory Advanced diGestive Neuroendocrine Carcinomas Treated With tARlatamab (clinicaltrials.gov) - P2 | N=1 | Terminated | Sponsor: Grupo Espanol de Tumores Neuroendocrinos | N=87 ➔ 1 | Trial completion date: Dec 2028 ➔ Sep 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2028 ➔ Sep 2026; AMGEN, due to a change in priorities within the Tarlatamab programme, has decided to withdraw its support for the study, which means the clinical trial will be terminated early.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Endocrine Cancer • Gastrointestinal Cancer • Gastrointestinal Neuroendocrine Carcinoma • Neuroendocrine Carcinoma • Oncology • Solid Tumor • DLL3

RAGNAR: Refractory Advanced diGestive Neuroendocrine Carcinomas Treated With tARlatamab (clinicaltrials.gov) - P2 | N=87 | Active, not recruiting | Sponsor: Grupo Espanol de Tumores Neuroendocrinos | Recruiting ➔ Active, not recruiting

Enrollment closed • Endocrine Cancer • Gastrointestinal Cancer • Gastrointestinal Neuroendocrine Carcinoma • Neuroendocrine Carcinoma • Oncology • Solid Tumor • DLL3

T-cell redirecting therapies in lung cancer - a comprehensive analysis of clinical trials. (PubMed, Front Immunol) - "Among these, tarlatamab, a DLL3×CD3 BiTE, has achieved the most advanced clinical validation, receiving traditional FDA approval in November 2025 for second-line ES-SCLC following Phase 3 DeLLphi-304 data demonstrating superior overall survival versus chemotherapy (median 13.6 vs. 8.3 months; HR 0.60). TIL therapy is the leading adoptive cell approach in non-small cell lung cancer (NSCLC), with lifileucel demonstrating a 25.6% ORR in anti-PD-1-resistant disease and a 64.3% ORR when combined with pembrolizumab in ICI-naïve patients, though manufacturing complexity and cost constrain broad access...Combination strategies pairing T cell-redirected therapies with ICIs, antibody-drug conjugates, and allogeneic or innate immune effectors represent the most promising path toward durable benefit. As the field advances toward Phase 3 trials, biomarker-selected patient populations, and scalable allogeneic manufacturing platforms, T cell-redirected therapy is positioned..."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

γδ T cells modulate anti-tumor immunity in small cell lung cancer. (PubMed, Cancer Cell) - "Moreover, using preclinical models, we demonstrated that γδ T cells are effective at tarlatamab (delta-like ligand 3 [DLL3]-CD3 bispecific T cell engager [BiTE])-redirected SCLC killing and that zoledronate, an FDA-approved compound, can sensitize SCLC cells to γδ T cell-mediated killing. Thus, our findings suggest that engaged γδ T cells are potentially valuable targets for SCLC therapy."

IO biomarker • Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3 • PD-1

News on the therapeutic management of small-cell lung cancer (ERS 2026) - "This presentation will summarize the key advances that have transformed the clinical management of small-cell lung cancer, both in limited-stage and extensive-stage disease, with a particular focus on consolidation therapy with durvalumab following chemoradiotherapy, maintenance therapy combining lurbinectedin and atezolizumab in the first-line setting for metastatic disease, as well as the emergence of DLL3 directed T-cell engagers, such as tarlatamab. It will also explore emerging strategies, such as new antibody-drug conjugates, and examine how these advances are redefining treatment sequences, clinical practice, and future therapeutic approaches."

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

Navigating tarlatamab and bispecific T-cell engager therapy in small cell lung cancer: A narrative review. (PubMed, Cancer Treat Res Commun) - "Furthermore, we address the critical operational hurdles, including step-up dosing schedules and the logistical considerations for transitioning from inpatient monitoring to outpatient administration. Finally, the review analyzes emerging data on resistance mechanisms such as antigen downregulation and T-cell exhaustion to provide evidence-based guidance on patient selection and future treatment sequencing strategies."

Journal • Review • Hematological Disorders • Hematological Malignancies • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

DeLLphi-303: First-Line Tarlatamab in Combination With Carboplatin, Etoposide, and PD-L1 Inhibitor in Subjects With Extensive Stage Small Cell Lung Cancer (ES-SCLC) (clinicaltrials.gov) - P1 | N=184 | Active, not recruiting | Sponsor: Amgen | Trial completion date: Aug 2028 ➔ May 2030 | Trial primary completion date: Aug 2028 ➔ May 2030

Trial completion date • Trial primary completion date • 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=350 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

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

Tarlatamab as second-line (2L) treatment for small cell lung cancer (SCLC): Outcomes by chemotherapy-free interval (CFI) and prior PD-(L)1 inhibitor use in the phase III DeLLphi-304 trial (ESMO 2025) - P3 | "Methods Patients were randomised 1:1 to tarlatamab or CTx (topotecan, lurbinectedin, or amrubicin) Post hoc analysis was conducted for prespecified subgroups based on CFI (< 90 vs ≥ 90 days) and prior anti-PD-(L)1 use (yes vs no). Additionally, in contrast to CTx, the reduced risk of death and higher ORR with tarlatamab remained consistent even in platinum-resistant disease where prognosis has been especially poor, reinforcing tarlatamab as a standard of care for 2L SCLC. Table: LBA101 CFI Tarlatamab CTx Tarlatamab CTx < 90 days ≥ 90 days Efficacy n = 109 n = 114 n = 145 n = 141 Median OS, mos 10.9 6.4 17.1 10.6 HR (95% CI) 0.60 (0.43, 0.84) 0.65 (0.45, 0.93) Median PFS, mos 3.2 2.7 4.5 4.4 HR (95% CI) 0.71 (0.54, 0.94) 0.73 (0.56, 0.95) Safety n = 107 n = 109 n = 145 n = 135 Grade ≥ 3 TRAEs, % 30 58 24 66 TRAE leading to dose interruption or reduction, % 21 50 18 59 CRS, % 59 - 54 - Prior PD-(L)1 Yes No Efficacy n = 180 n = 180 n = 74 n = 75 Median OS, mos..."

Clinical • Late-breaking abstract • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

MO15. Expanding Therapeutic Frontiers in SCLC: ADCs, T-Cell Engagers, and First-Line Strategies (IASLC-WCLC 2026) - "This mini oral session presents nine selected abstracts covering key advances in SCLC, including first-line and perioperative treatment strategies, novel B7-H3-targeted antibody-drug conjugates, and emerging tarlatamab regimens with associated immunotherapy biomarkers."

ADC • Clinical • IO biomarker • Lung Cancer • Small Cell Lung Cancer • Solid Tumor

Tarlatamab in Patients With Advanced DLL3-Expressing Tumors: Updated Results From a Single Arm Phase 2 Basket Trial (IASLC-WCLC 2026) - "Treatment was well tolerated in the Stage 1 cohort, with manageable toxicities and no high-grade CRS or ICANS events. Enrollment has begun for Stage 2."

Clinical • Metastases • P2 data • Endocrine Cancer • Genito-urinary Cancer • Genitourinary Neuroendocrine Carcinoma • Lung Adenocarcinoma • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Neoplasm • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

MERLIN, Tarlatamab Treatment for Limited Small Cell Lung Cancer in Patients in Maintenance: A Phase II Clinical Trial (IASLC-WCLC 2026) - "Exploratory endpoints include the evaluation of tumour microenvironment characteristics and peripheral immune biomarkers and their association with clinical outcomes. The distribution of time-to-event endpoints will be estimated using the Kaplan-Meier method."

Clinical • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

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 | "Methods : Patients with ES-SCLC were eligible if they had completed 4 to 6 cycles of 1L platinum-etoposide chemotherapy and anti-PD-L1 (unless unavailable) without disease progression. Within 8 weeks from the start of the last chemo-immunotherapy cycle, patients received tarlatamab (10 mg IV Q2W) with either atezolizumab (1680 mg IV Q4W) or durvalumab (1500 mg IV Q4W) as 1L maintenance until disease progression...The median OS was 25.3 months (95% CI, 20.3-not reached) and the median PFS was 5.6 months (95% CI, 3.5-9.0) (Figure). Conclusions Tarlatamab in combination with anti-PD-L1 demonstrated an acceptable safety profile, with long-term tolerability and unprecedented OS."

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

Ablative Radiotherapy Meets T-Cell Engagement: SABR During Tarlatamab in Oligoprogressive ES-SCLC (ESMO 2026) - No abstract available

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

Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: results from the phase 3 DeLLphi-304 trial. (PubMed, Lung Cancer) - "In addition to its previously reported antitumor activity, tarlatamab demonstrated clinically meaningful improvements in symptoms and HRQoL compared with SoC. These findings support a favorable benefit-risk profile of tarlatamab in patients previously treated for ES-SCLC."

Journal • P3 data • Cough • Lung Cancer • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor

Phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer (NEPC). (ASCO 2024) - P1 | "Findings from this phase 1 study of tarlatamab in pts with NEPC demonstrated manageable safety with encouraging anti-tumor activity in DLL3 expressing NEPC. Further investigation is ongoing."

IO biomarker • P1 data • Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Metastatic Castration-Resistant Prostate Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

Tarlatamab Real-World Use and Early Effectiveness Outcomes in Patients With Previously Treated Small Cell Lung Cancer (IASLC-WCLC 2026) - "Additionally, most patients (71%) were treated with an anti-PD-L1 agent in 1L, and among them, 71% received atezolizumab. Conclusions : Early real-world survival outcomes with tarlatamab were consistent with clinical trial findings, despite broader use across diverse SCLC populations and practice settings. Updated analyses with larger sample size and longer follow-up are planned."

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

Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy. (PubMed, N Engl J Med) - P3 | "Treatment with tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. (Funded by Amgen; DeLLphi-304 ClinicalTrials.gov number, NCT05740566.)."

Journal • Cough • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor

Tarlatamab in previously treated small cell lung cancer (SCLC): DeLLphi-300 phase I study long-term outcomes and intracranial activity (ELCC 2024) - P1 | "Table: 195MO ORR mDOR mPFS mOS % (95% CI) mos (95% CI) Tarlatamab (N = 152)a 25.0 (18.3, 32.7) 11.2 (6.6, 22.3) 3.5 (2.7, 3.8) 17.5 (11.4, NE) 10 mg (n = 17)b 35.3 (14.2, 61.7) 14.9 (3.0, NE) 4.0 (1.6, 11.0) 20.3 (5.1, NE) 30 mg (n = 8)b 12.5 (0.3, 52.7) 3.8 (NE, NE) 1.8 (1.1, NE) 7.2 (1.5, NE) 100 mg (n = 76)b 19.7 (11.5, 30.5) 22.3 (5.6, NE) 3.7 (1.9, 4.5) 17.5 (11.7, NE) 100 mg (eIV) (n = 32)c 37.5 (21.1, 56.3) 6.5 (3.5, 11.2) 3.8 (1.7, 5.7) 12.6 (7.9, NE) Other (n = 19)d 21.1 (6.1, 45.6) NE (6.8, NE) 2.8 (2.1, 3.5) NE (6.0, NE) aDCO 2 Oct 2023 b1-step dosing: 1 mg (Day 1); target dose: Days 8, 15, then Q2W cCohorts: 30 mg eIV → 100 mg Q2W; 100 mg eIV → 100 mg Q2W dCohorts: 1 → 25 → 100 mg Q2W; 1 → 100 → 200 mg Q3W; 1 → 100 mg D1/D8 eIV, extended IV; NE, not estimable Conclusions In longer follow-up of DeLLphi-300, tarlatamab demonstrated durable responses and unprecedented survival outcomes in previously treated SCLC. While limited to analyses of treated, stable..."

P1 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Detailed safety analysis of DeLLphi-304: The first phase III study to evaluate tarlatamab versus chemotherapy for previously treated small cell lung cancer (ESMO 2025) - P3 | "Methods Pts were randomized to tarlatamab or chemotherapy (CTx: topotecan, lurbinectedin, or amrubicin). Conclusions In the DeLLphi-304 trial, tarlatamab demonstrated a predictable and manageable safety profile in 2L SCLC, with no new safety signals identified. Table: LBA100 Treatment-related adverse events TRAE Tarlatamab (n = 252) CTx (n = 244) All Grades Grade ≥3 All Grades Grade ≥3 Anemia 19.8% 2.0% 61.5% 27.9% Neutropenia 7.5% 4.4% 29.5% 22.1% Thrombocytopenia 3.2% 0.4% 23.8% 11.8% Infection 6.3% 1.2% 15.2% 8.6%"

Clinical • Late-breaking abstract • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • DLL3

Successful off-label treatment of two immune checkpoint inhibitor-refractory, metastatic mucosal melanomas with the DLL3-directed T-cell engager tarlatamab (ADO 2026) - No abstract available

Checkpoint inhibition • Metastases • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • DLL3

T-Cell Engagers in Lung Cancer: A Comprehensive Literature Review from Tarlatamab Approval to Next-Generation Strategies. (PubMed, Cancers (Basel)) - "Tarlatamab approval validates the TCE platform in lung cancer, but overcoming TME-mediated resistance, antigen heterogeneity, and class-specific toxicities including cytokine release syndrome remains the central challenge. Rational TCE design, incorporating costimulatory signaling, antigen selection informed by parallel ADC validation data, and evidence-based combination strategies, offers the most credible path toward expanding this platform's impact in metastatic lung cancer."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • CD70 • CLDN18 • DLL3 • FOLR1 • HER-2

Next-generation antibody-based therapeutics in cancer: antibody-drug conjugates bispecific antibodies across hematologic malignancies and solid tumors. (PubMed, J Hematol Oncol) - "ADCs such as trastuzumab deruxtecan have expanded the concept of targetable HER2 expression, demonstrating meaningful intracranial activity and redefining standards of care in HER2-low breast cancer and beyond...In solid tumors, EGFR‑MET and DLL3‑targeted bsAbs have delivered clinically validated efficacy in historically refractory settings, including regulatory approval of tarlatamab...Next‑generation strategies-bispecific ADCs, probody‑drug conjugates, and immune‑stimulating antibody conjugates-combined with immunotherapy partnerships hold promise for overcoming resistance and improving therapeutic indices. By distilling pivotal clinical data and highlighting unresolved questions, this review provides a roadmap for translating antibody‑based innovations into precision oncology."

IO biomarker • Journal • Review • Acute Lymphocytic Leukemia • B Cell Lymphoma • Breast Cancer • Hematological Disorders • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD20 • CD276 • CLDN18 • DLL3 • EGFR • ERBB3 • HER-2

Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study (ESMO 2025) - P1 | "c Fatal TRAE of septic shock related to platinum-etoposide chemotherapy. Conclusions The combination of tarlatamab with chemo-IO for 1L treatment of ES-SCLC demonstrated manageable safety with encouraging initial survival outcomes, supporting further investigation of this combination in the phase III DeLLphi-312 study."

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