Imdelltra (tarlatamab-dlle) / Amgen 
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  • ||||||||||  Imdelltra (tarlatamab-dlle) / Amgen
    Review, Journal:  Bispecific T-cell engagers (BiTE): a review of tarlatamab in small cell lung cancer. (Pubmed Central) -  Jul 5, 2025   
    Tarlatamab's use must be evaluated in a more heterogeneous population with different demographics, comorbidities, and a larger patient population. The possibility of combination therapy studies should also be evaluated in future studies to increase the efficacy of tarlatamab.
  • ||||||||||  Review, Journal:  Bispecific Antibodies in Solid Tumors: Advances and Challenges. (Pubmed Central) -  Jun 26, 2025   
    Currently, several BsAbs are under clinical development for solid tumors, but are mostly in early phase I and II trials. This review provides an overview of the basic mechanism of action of BsAbs, current FDA-approved BsAbs, and current BsAbs under clinical development, their challenges in clinical use, the management of toxicities, and future directions.
  • ||||||||||  Review, Journal, PD(L)-1 Biomarker, IO biomarker:  Treatment of small cell lung cancer; advances and future prospects. (Pubmed Central) -  Jun 12, 2025   
    Two randomized phase III studies (IMpower 133 and CASPIAN) demonstrated that addition of atezolizumab or durvalumab to platinum plus etoposide prolonged the overall survival in ES-SCLC patients...Tarlatamab is a bispecific antibody that targets DLL3 and CD3...Further development of effective treatments and additional biomarkers to predict efficacy is needed. Bispecific antibodies and/or antibody-drug conjugate could be the next candidates for breakthroughs in the treatment of SCLC.
  • ||||||||||  Journal:  Small Cell Lung Cancer: A Review. (Pubmed Central) -  Jun 3, 2025   
    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:  Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy. (Pubmed Central) -  Jun 2, 2025   
    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.).
  • ||||||||||  Imdelltra (tarlatamab-dlle) / Amgen
    Review, Journal, IO biomarker:  Taking a Bite Out of Small Cell Lung Cancer By Leveraging Precision-Directed Delta-Like Ligand-3 Therapies. (Pubmed Central) -  May 29, 2025   
    The therapeutic landscape of small cell lung cancer (SCLC) is undergoing a paradigm shift with the emergence of delta-like ligand-3 (DLL3)-directed therapies, particularly tarlatamab, a first-in-class bispecific T-cell engager designed to bind to cluster of differentiation-3 on T cells and DLL3 on tumors cells, demonstrating promising efficacy, including potential intracranial activity, and a manageable safety profile...Importantly, the thoughtful incorporation of toxicity mitigation strategies, equitable access, and multidisciplinary care models will be critical to ensure that clinical advances translate into meaningful, real-world benefits. The challenge ahead lies in balancing efficacy with patient quality of life, financial burden, and time toxicity, an effort that requires continuous innovation, collaboration, and a patient-centered approach.
  • ||||||||||  Imdelltra (tarlatamab-dlle) / Amgen, ifinatamab deruxtecan (DS-7300) / Daiichi Sankyo, Merck (MSD), Trodelvy (sacituzumab govitecan-hziy) / Gilead
    Review, Journal:  ADCs and TCE in SCLC Therapy: The Beginning of a New Era? (Pubmed Central) -  May 27, 2025   
    These therapies represent a paradigm shift from traditional monoclonal antibody (mAb) and chemotherapy regimens, allowing direct engagement of multiple targets associated with tumor progression. In this review, we provide an overview of current drug development in SCLC, specifically focusing on these new agents, summarizing available evidence, and tracking future directions.
  • ||||||||||  Zepzelca (lurbinectedin) / PharmaMar, Jazz
    Real-world effectiveness of lurbinectedin in extensive stage small cell lung cancer (ES-SCLC). () -  Apr 23, 2025 - Abstract #ASCO2025ASCO_6343;    
    If the median TTD can be considered a potential surrogate for progression free survival (PFS), then we would have a PFS of 3 months which is slightly shorter in our cohort compared to 3.5 months reported by Trigo et al in their original paper. Retrospective nature of the study and lack of control group, however, limit the predictor variables.
  • ||||||||||  ZL-1310 / ZAI Lab
    ZL-1310, a DLL3 ADC, in patients with extensive stage small cell lung cancer: Ph1 trial update. (Hall A - Posters and Exhibits; Poster Bd #: 356) -  Apr 23, 2025 - Abstract #ASCO2025ASCO_3657;    
    P1
    ZL-1310 demonstrated a tolerable safety profile and promising antitumor activity in r/r ES-SCLC, including pts with brain metastases, pt with prior tarlatamab, and in the setting of low DLL3 expression. Updated data, including patients in the randomized Part 2 dose optimization, will be presented.
  • ||||||||||  Imdelltra (tarlatamab-dlle) / Amgen
    Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): Primary analysis of Ph3 DeLLphi-304. (Arie Crown Theater) -  Apr 23, 2025 - Abstract #ASCO2025ASCO_1529;    
    P3
    The DeLLphi-304 trial showed tarlatamab significantly improved OS, PFS, and PROs, with a favorable safety and tolerability profile compared to CTx in pts with SCLC that progressed on or after initial platinum-based CTx, defining a new standard of care for these patients. Clinical Trial Information: NCT05740566; Legal entity responsible: Amgen Inc.; Funding: Amgen Inc.; Editorial acknowledgement: Medical writing support for the development of this abstract was provided by Sukanya Raghuraman, PhD, of Cactus Life Sciences, part of Cactus Communications, and was funded by Amgen Inc.
  • ||||||||||  Review, Journal, IO biomarker:  Expanding the Therapeutic Reach of Chimeric Antigen Receptor T-Cells and Bispecific T-Cell Engagers Across Solid Tumors. (Pubmed Central) -  Mar 27, 2025   
    In this review, we discuss the landmark data that led to the commercialization of four novel FDA-approved T-cell-based therapeutics in solid malignancies, including tarlatamab for small cell lung cancer, afamitresgene autoleucel for synovial sarcoma, lifileucel for metastatic melanoma, and tebentafusp for metastatic uveal melanoma...Some solutions include addressing on-target, off-tumor toxicity; improving the manufacturing of CARs; optimizing the tissue-specific tumor microenvironment by combating immune desert tumors; and discovering natural tumor neoantigens and non-self-epitopes generated by tumor-specific mutations. These concepts can help provide transformative benefits for patients with solid malignancies in the coming years.
  • ||||||||||  LBL-058 / Leads Biolabs
    LBL-058, A novel T cell engager conjugate (TEC) targeting DLL3 with dual tumor suppressive functions. (Section 40; Poster Board No: 8) -  Mar 25, 2025 - Abstract #AACR2025AACR_9287;    
    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.
  • ||||||||||  Imdelltra (tarlatamab-dlle) / Amgen
    AI-guided engineering and development of anti-DLL3-targeting T cell engagers (TCEs) (Section 40; Poster Board No: 5) -  Mar 25, 2025 - Abstract #AACR2025AACR_9284;    
    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.
  • ||||||||||  Imdelltra (tarlatamab-dlle) / Amgen, ifinatamab deruxtecan (DS-7300) / Daiichi Sankyo, Merck (MSD), Rova-T (rovalpituzumab tesirine) / AbbVie
    Bispecific antibody drug conjugates (bsADCs) targeting DLL3 and B7-H3 demonstrated potent anti-tumor activity in preclinical models of small cell lung cancer (SCLC) (Section 37; Poster Board No: 22) -  Mar 25, 2025 - Abstract #AACR2025AACR_8181;    
    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.
  • ||||||||||  Imdelltra (tarlatamab-dlle) / Amgen, Rova-T (rovalpituzumab tesirine) / AbbVie
    AI-guided engineering and preclinical development of biparatopic anti-DLL3 antibody-drug conjugates (ADCs) (Section 36; Poster Board No: 8) -  Mar 25, 2025 - Abstract #AACR2025AACR_6971;    
    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.
  • ||||||||||  Imdelltra (tarlatamab-dlle) / Amgen
    Combination surface targeting strategies in relapsed small cell lung cancer (SCLC) to overcome intratumoral heterogeneity associated with treatment resistance (Section 17; Poster Board No: 2) -  Mar 25, 2025 - Abstract #AACR2025AACR_5404;    
    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.