Imdelltra (tarlatamab-dlle) / Amgen, BeiGene - LARVOL DELTA

Small Cell Lung Cancer: A Review. (PubMed, JAMA) - "First-line treatment for ES-SCLC is combined treatment with platinum-etoposide chemotherapy and immunotherapy with the programmed cell death 1 ligand 1 (PD-L1) inhibitors durvalumab or atezolizumab followed by maintenance immunotherapy until disease progression or toxicity...Second-line therapy for patients with ES-SCLC includes the DNA-alkylating agent lurbinectedin (35% overall response rate; median progression-free survival, 3.7 months) and a bispecific T-cell engager against delta-like ligand 3, tarlatamab (40% overall response rate; median progression-free survival, 4.9 months)...First-line treatment for LS-SCLC is radiation targeting the tumor given concurrently with chemotherapy and followed by consolidation immunotherapy. For ES-SCLC, first-line treatment is chemotherapy and immunotherapy followed by maintenance immunotherapy."

Journal • Cough • Endocrine Cancer • Lung Cancer • Musculoskeletal Pain • Neuroendocrine Tumor • Oncology • Pain • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor

Tarlatamab-induced immune-related adverse events: Retrospective real-world pharmacovigilance study using FAERS database. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Adverse events • Real-world • Real-world evidence • Retrospective data • Palliative care

Optimizing tarlatamab therapy for relapsed small cell lung cancer: Biomarker identification and addressing treatment delivery disparity. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

Real world outcomes of patients treated with tarlatamab in extensive stage small cell lung cancer. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

Real-world safety and efficacy of tarlatamab in patients with small cell lung cancer or extrapulmonary small cell carcinoma. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

Administration of tarlatamab in an outpatient setting utilizing remote patient monitoring: Mayo Clinic experience. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical

Implementation of tarlatamab treatment for small cell lung cancer using an outpatient care program. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

Real-world efficacy and safety of tarlatamab in patients with relapsed extensive-stage small cell lung cancer. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): Primary analysis of Ph3 DeLLphi-304. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT05740566 The abstract will be released to the public on June 2, 2025 at 8:00 AM EDT"

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

A phase 2 basket trial of tarlatamab in patients with advanced DLL3-expressing tumors: University of California Lung Cancer Consortium UCCC-01/UCLA L-10. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06788938 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P2 data • Pan tumor • Lung Cancer • Oncology • Solid Tumor • DLL3

Tarlatamab for Extensive-Stage Small Cell Lung Cancer (ASCO 2025) - No abstract available

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

Advances in adoptive cell therapies in small cell lung cancer. (PubMed, Explor Target Antitumor Ther) - "While investigated therapies such as rovalpituzumab tesirine (Rova-T) have failed, several insights from these trials have led to the development of compelling new agents such as sacituzumab govitecan (SG), ifinatamab deruxtecan (I-DXd), tarlatamab, and DLL3-targeted CAR-T cells. Advancing development of molecular testing and improving targeted approaches remain integral to pushing forward the progress of adoptive cell therapies in SCLC."

IO biomarker • Journal • Review • Gene Therapies • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3

Improving Communication Between Inpatient and Outpatient Nursing for Multidisciplinary Clinical Trials (ONS 2025) - "In 2023, our team opened a trial introducing a novel investigational treatment, Tarlatamab, for small cell lung cancer (SCLC) patients requiring treatment in both the in- and outpatient setting...Our research team was able to adjust communication methods and tools with a multi-disciplinary approach to support quality treatment options for our SCLC patients. We are seeing more trials needing inpatient care so these frameworks of communication perpetuate future needs of clinical trials."

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

LBL-058, A novel T cell engager conjugate (TEC) targeting DLL3 with dual tumor suppressive functions. (AACR 2025) - "Nowadays, many DLL3-targeting therapies are in development among them Tarlatamab, which is a T cell engager (TCE), has been approved by FDA for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy, at the same time several DLL3 targeting ADCs were also showing some promising results. LBL-058 has the potential to be a First-In-Class DLL3-targeted TCE ADC, which combines the anti-tumor properties of TCE and ADC, and shows a potent and durable anti-tumor activity and is expected to provide clinical benefits for the treatment of patients with SCLC."

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

AI-guided engineering and development of anti-DLL3-targeting T cell engagers (TCEs) (AACR 2025) - "An anti-DLL3 x CD3 bispecific T-cell engager (TCE), tarlatamab, has demonstrated significant clinical benefits and was recently approved by the US FDA for the treatment of DLL3-expressing SCLC...Our leading TCE molecule demonstrated a robust DLL3-specific T cell-dependent cellular cytotoxicity towards several tumor cell lines with various DLL3 expression levels, including both cisplatin-sensitive (e.g., NCI-H209, NCI-H526, DMS153) and cisplatin-resistant (e.g., SHP-77) cell lines. The biparatopic DLL3-target TCE also showed significant tumor inhibitory activity in tumor xenograft models including SHP-77, NCI-H82, and DMS-53. Taken together, our data underscore the significant utility of AI-guided platform in antibody/protein engineering, and support further development of our biparatopic anti-DLL3 x CD3 TCE in the treatment of DLL3-expressing SCLC and other NECs."

IO biomarker • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

ZW209, a DLL3 targeted trispecific T cell engager with integrated CD28 co-stimulation, demonstrates safety and potent preclinical efficacy in models of small cell lung cancer (AACR 2025) - "Bispecific T cell engagers (TCE) targeting DLL3, including tarlatamab which has received accelerated approval, have demonstrated anti-tumor activity in the clinic with an improved duration of response compared to current standard of care, including chemotherapy and immunotherapy. Importantly, a ZW209 cynomolgus cross-reactive surrogate molecule displayed a favorable safety profile as it was well tolerated in non-human primates with repeat dosing at 10 mg/kg with no abnormal clinical signs.In summary, these preclinical data support that ZW209 promotes improved anti-tumor activity against DLL3-positive cancer cells relative to competitor bispecific TCEs. By integrating CD28 co-stimulation into our trispecific T cell engager, ZW209 has the potential to improve the rate and duration of response for better clinical outcomes."

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

Preclinical evaluation of CD3/DLL3 bispecific antibody in syngeneic and humanized mouse models for solid tumor treatment (AACR 2025) - "In PBMC-reconstituted B-NDG mice implanted with human tumor cell line SHP-77, Tarlatamab analog (in house) almost completely suppresses tumor growth. These results indicate that both preclinical animal models can be used to evaluate the in vivo efficacy of the CD3/DLL3 BsAb treatment."

Preclinical • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • CAFs • DLL3

Bispecific antibody drug conjugates (bsADCs) targeting DLL3 and B7-H3 demonstrated potent anti-tumor activity in preclinical models of small cell lung cancer (SCLC) (AACR 2025) - "Tarlatamab, a T cell engager targeting DLL3, was recently approved for SCLC...In vitro, the bsAbs showed superior internalization in double positive cell lines than the parental monovalent arms and outperformed the naked antibodies of DS-7300 and rovalpituzumab (Rova)...The bsAbs for our lead bsADCs exhibited excellent stability under stress conditions, suggesting their suitability for CMC development. In summary, our DLL3xB7H3 bsADCs showed promising and superior in vitro and in vivo preclinical activities with first-in-class potential for SCLC treatment."

Preclinical • Brain Cancer • CNS Tumor • Endocrine Cancer • Glioblastoma • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3

Preclinical study of bispecific antibody drug conjugates (bsADCs) targeting DLL3 and SEZ6 demonstrated potent anti-tumor activity in small cell lung cancer (SCLC) xenograft models (AACR 2025) - "Tarlatamab, a T cell engager targeting DLL3, was recently approved for SCLC...In vivo, the bsADC exhibited robust anti-tumor efficacy in SCLC xenograft models. In summary, our DLL3xSEZ6 bsADC showed promising in vitro and in vivo preclinical activities with first-in-class potential for treatment of SCLC."

Preclinical • Brain Cancer • CNS Tumor • Endocrine Cancer • Glioblastoma • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3 • SEZ6 • TOP1

AI-guided engineering and preclinical development of biparatopic anti-DLL3 antibody-drug conjugates (ADCs) (AACR 2025) - "An anti-DLL3 x CD3 bispecific T-cell engager, tarlatamab, has demonstrated significant clinical benefits and was recently approved by the US FDA for the treatment of DLL3-expressing SCLC. On the other hand, Rova-T, the first antibody-drug conjugate (ADC) targeting DLL3 entered advanced clinical development, failed in phase III studies due to insufficient efficacy and an unfavorable safety profile...The ADCs showed selective cytotoxicity towards multiple tumor cell lines with varying levels of DLL3 expression in vitro, and potently inhibited the growth of several DLL3-expressing tumor xenografts in animal models. Taken together, our findings underscore the significance of AI-guided antibody engineering and optimization, and provide support for the further development of the biparatopic anti-DLL3 ADCs in patients with DLL3-expressing tumors such as SCLC and other neuroendocrine tumors."

Preclinical • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Combination surface targeting strategies in relapsed small cell lung cancer (SCLC) to overcome intratumoral heterogeneity associated with treatment resistance (AACR 2025) - "Following decades of, at best, modest clinical advances, 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...We show that combination targeting against different surface proteins (e.g., DLL3, TROP2, HER2) using both immune (i.e., chimeric antigen receptor T-cells, BiTEs) and payload-based modalities (i.e., ADCs) was more effective than single-agent targeting in resistant, neuroendocrine-low models. Therefore, intratumoral heterogeneity associated with relapsed SCLC, which limits efficacy of single-agent surface targeting strategies, may be exploited with combinatorial therapies to target resistant cell populations, including DTPCs, using payload and immune-based methods."

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

Optimization of tarlatamab step-up dosing regimen to mitigate cytokine release syndrome using quantitative systems pharmacology modeling (AACR 2025) - "This dose optimization might lower the probability of CRS grade 3 events observed in patients treated with 100 mg.Split-dose regimens and regimens with more than one step-up dose allow for minimizing CRS incidence without compromising the efficacy of TCEs. QSP modeling is a useful tool to investigate various doses and regimens of bispecific and multispecific antibodies."

Cytokine release syndrome • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

IMDELLTRA DEMONSTRATED SUPERIOR OVERALL SURVIVAL IN SMALL CELL LUNG CANCER (PRNewswire) - P3 | N=509 | DeLLphi-304 (NCT05740566) | Sponsor: Amgen | "Amgen...today announced that the global Phase 3 DeLLphi-304 clinical trial evaluating IMDELLTRA (tarlatamab-dlle) as a treatment for patients with small cell lung cancer (SCLC) who progressed on or after a single line of platinum-based chemotherapy met its primary endpoint at a planned interim analysis. IMDELLTRA demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) compared to local standard-of-care (SOC) chemotherapy....The safety profile for IMDELLTRA was consistent with its known profile. Detailed data from DeLLphi-304 will be presented at an upcoming medical congress."

P3 data • Small Cell Lung Cancer

Safety of tarlatamab with 6-8-h outpatient versus 48-h inpatient monitoring during cycle 1: DeLLphi-300 phase 1 substudy. (PubMed, ESMO Open) - "Safety outcomes, including hospitalization rates, were similar in this first-in-human study following tarlatamab 10 mg Q2W administration with 6-8-h outpatient versus 48-h inpatient monitoring in cycle 1."

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

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 | Not yet recruiting ➔ Recruiting

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