- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
B-NDG MHC I/II DKO mice plus: A refined humanized model for evaluating T cell engager efficacy and toxicity (Section 8) - Mar 17, 2026 - Abstract #AACR2026AACR_9447;
B-NDG MHC I/II DKO mice plus effectively alleviate human PBMC-induced GvHD while retaining normal antibody pharmacokinetics and enabling reliable assessment of TCE anti-tumor efficacy and cytokine-mediated toxicity. This model provides a refined and translationally relevant platform for preclinical evaluation of TCE therapeutics.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Tumor cell surface targeting of high-grade neuroendocrine carcinomas (Section 16) - Mar 17, 2026 - Abstract #AACR2026AACR_7632;
DLL3 levels have been evaluated by CLIA-validated immunohistochemistry in >340 patients at MDACC, including those diagnosed with rare extrapulmonary hgNECs (i.e., Merkel cell carcinoma, small cell of the breast, thyroid, etc.) for off-label use of tarlatamab (DLL3-targeting TCE)...Surface-targeting therapies represent a new paradigm for hgNEC therapeutics and while DLL3- and SEZ6-targeting therapies are showing promise across all hgNECs, their impact will be limited outside SCLC without patient selection. Utilizing biomarkers, including those for target expression, inflammatory potential, and payload sensitivity, will be critical to optimize drug selection for patients with these malignancies.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Analysis of RNA expression of 47 cell surface proteins in real-world small cell lung cancer patients (Section 46) - Mar 17, 2026 - Abstract #AACR2026AACR_6881;
The biparatopic DLL3/CD3 TCE exhibits robust preclinical efficacy and a favorable safety profile, supporting its further development as a targeted immunotherapy for DLL3-positive SCLC and NECs. Almost all patients relapse after initial induction chemotherapy and immunotherapy, and clinical benefit from subsequent therapies including tarlatamab-dlle (a DLL3 bispecific T cell engager) are limited...With respect to treatment status, we detected significantly (p<0.05) higher expression of CTLA4, PDCD1, TIGIT, TACSTD2, and ITGB6 in treatment-na
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen, xaluritamig (AMG 509) / Amgen, IBI-389 / Innovent Biologics
An integrated preclinical platform for comprehensive evaluation of T-Cell engagers (Section 29) - Mar 17, 2026 - Abstract #AACR2026AACR_5220;
AMG509 (targeting STEAP1), AMG757 (targeting DLL3), and IBI-389 (targeting CLDN18.2) were evaluated in models of prostate cancer, small-cell lung cancer, and patient-derived xenografts (PDX), respectively. In the BALB/c-hCD3EDG syngeneic model, administration of the CD3/CD20 bispecific antibody led to 81.5% tumor growth inhibition after 18 days.GemPharmatech's integrated strategy
- |||||||||| CS5008 / CStone Pharma
Preclinical efficacy and safety of CS5008, a novel SSTR2 (Section 17) - Mar 17, 2026 - Abstract #AACR2026AACR_4690;
Its favorable preclinical safety and robust PK support further clinical development. An IND application is expected by the end of 2026.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
VHH nanobody-masked conditionally active CDH17 T cell engager for colorectal cancer (Section 10) - Mar 17, 2026 - Abstract #AACR2026AACR_4615;
P1/2
TCEs have demonstrated convincing efficacy in multiple blood cancers and have recently with Tarlatamab made breakthrough in solid tumors...WuXi Biologics has developed a conditionally active CDH17 TCE with the proprietary VHH-masked CD3 TCE platform. The molecule has demonstrated great efficacy and better tolerability preclinically, and is to be further evaluated in the clinic.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Development of a T cell engager against IGFBPL1: A novel target for small cell lung cancer and other neuroendocrine cancers (Section 10) - Mar 17, 2026 - Abstract #AACR2026AACR_4601;
FDA approval of tarlatamab, a T cell engager targeting DLL3, has delivered a new treatment option for patients with relapsed disease and spurred enthusiasm for T cell engagers and other DLL3-targeted therapies for SCLC...Our data support development of a novel T cell engager for SCLC based on IGFBPL1 targeting. This potential therapy provides another option to DLL3-targeting therapies in the clinic and under investigation, to overcome this challenging and devastating disease.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen, daraxonrasib (RMC-6236) / Revolution Medicines
Dual dependency of large cell neuroendocrine carcinoma on Ras and ASCL1 oncogenic pathways (Section 15) - Mar 17, 2026 - Abstract #AACR2026AACR_3303;
This is unexpected, as forced Ras expression inhibits SCLC proliferation, and forced ASCL1 expression does the same in lung adenocarcinoma. Dual dependence on the Ras-activated kinase cascade and ASCL1 may be a defining feature of LCNEC, and we are now exploring therapeutic strategies to exploit this vulnerability.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
A novel DLL3 trispecific T cell engager antibody integrating the CD2/CD58 co-stimulatory pathway demonstrates superior antitumor efficacy and balanced safety profile (Room 33 - Upper Level - Convention Center) - Mar 17, 2026 - Abstract #AACR2026AACR_2621;
These challenges contribute to the narrow therapeutic window of TCEs in treating solid tumors and partially explain why no solid tumor-targeting TCE received regulatory approval until the DLL3-targeting tarlatamab became the first (and only to date) in 2024...In summary, the incorporation of a CD2 co-stimulatory moiety into a DLL3-targeting TCE leads to a novel, next-generation TCE with improved efficacy and safety profiles in preclinical studies. IND-enabling studies are ongoing with the potential to advance it to clinical studies in the near future.
- |||||||||| itareparib (NMS-293) / Nerviano Medical Sciences
PARPA-293-004: Phase Ib study of NMS-03305293, a brain-penetrant, non-trapping PARP1-selective inhibitor, in combination with temozolomide in relapsed ES-small cell lung cancer (Foyer) - Mar 6, 2026 - Abstract #ESMOTAT2026ESMO_TAT_87;
P1, P1/2
This lack of cross-reactivity poses clear disadvantages in their preclinical development, particularly for toxicity and safety evaluation in nonhuman primate models. Itareparib, being a true non-trapping agent, unlike Veliparib, is designed to combine with DNA-damagers, as it lacks ability to induce PARP
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
DLL3-directed T cell redirection as a therapeutic strategy for medullary thyroid cancer (Foyer) - Mar 6, 2026 - Abstract #ESMOTAT2026ESMO_TAT_54;
Tarlatamab is active against these models in vitro and in vivo, with the addition of T cells, and induces strong DLL3-dependent cytotoxicity and tumor suppression. Overall, these results provide preliminary preclinical support for DLL3-targeted T-cell engagement as a promising therapeutic strategy in MTC and warrants future clinical investigation.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Enrollment closed: DeLLphi-309: A Phase 2, Open-label, Randomized, Multicenter Study of Tarlatamab Dosing Regimens in Subjects With SCLC (clinicaltrials.gov) - Mar 3, 2026
P2, N=252, Active, not recruiting,
Overall, these results provide preliminary preclinical support for DLL3-targeted T-cell engagement as a promising therapeutic strategy in MTC and warrants future clinical investigation. Recruiting --> Active, not recruiting
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Real-world management of CRS-related fever in SCLC patients treated with the DLL3-targeted T-cell engager tarlatamab (Room 10 | Pacifico Yokohama North 3F G316+G317) - Mar 2, 2026 - Abstract #JSMO2026JSMO_994;
These findings emphasize the importance of early recognition and intervention, supporting safe outpatient introduction in selected patients and providing insight for multicenter studies and guideline development. Despite the limited cohort size, our data highlight practical aspects of CRS management and warrant validation in larger populations to refine supportive care frameworks.
- |||||||||| Small cell lung cancer and mesothelioma () - Mar 2, 2026 - Abstract #JSMO2026JSMO_517;
These immunotherapies are more effective in sarcomatoid/biphasic compared to epithelial. Additionally, nivolumab has also been shown to be effective against mesothelioma that does not involve the pleura.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Review, Journal: Early Experience with Tarlatamab (T-Cell Engagers) for Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Canada: Lessons Learned and Implementation Strategies. (Pubmed Central) - Feb 26, 2026
By sharing insights into administration protocols, dose ramp-up procedures, post-cycle 1 monitoring, and AE management strategies implemented at their centres, early adopters of tarlatamab can help other institutions develop and refine their own protocols more efficiently. Lessons learned during the early implementation phase, including the roles of various healthcare providers and the transition from inpatient to outpatient care, should facilitate the smoother integration of tarlatamab and other TCEs for solid tumours into clinical pathways across Canada.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Journal: Expression of antibody drug conjugate target antigens in ovarian sex cord stromal Tumors. (Pubmed Central) - Feb 22, 2026
The pervasive absence of HER2, folate receptor alpha, DLL3, TROP-2, and nectin-4 expression in SCSTs suggests ADCs targeting these antigens may be of limited clinical benefit. The design of clinical trials investigating the use of tissue factor-targeting ADCs for the treatment of adult GCTs warrants future consideration.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Emerging Clinical Development of Bispecific Antibodies including T-cell Engagers in the Field of Lung Cancer (Room 12 | Pacifico Yokohama North 4F G401+G402) - Feb 14, 2026 - Abstract #JSMO2026JSMO_273;
Recently, tarlatamab, a bispecific T cell-inducing antibody that simultaneously targets tumor antigens and T cells, has been approved for previously treated small cell lung cancer, and its use in clinical practice has begun...These novel immunotherapies enable multilayered control of tumor immunity and have the potential to overcome the limitations of ICI monotherapy. In this section, we will outline the latest clinical development trends of bispecific antibodies (including T cell-induced antibodies) in the field of lung cancer and discuss their position in future treatment strategies.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen, obrixtamig (BI 764532) / Boehringer Ingelheim, gocatamig (MK-6070) / Merck (MSD), Daiichi Sankyo
Journal: Structural and functional insights into CD3 bispecific antibodies targeting DLL3 in cancer immunotherapy. (Pubmed Central) - Feb 7, 2026
Not yet recruiting --> Recruiting | Trial completion date: Mar 2030 --> Aug 2030 | Initiation date: Sep 2025 --> Feb 2026 | Trial primary completion date: Sep 2028 --> Feb 2029 This study systematically characterized three clinical-stage CD3
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
DeLLphi-312 phase III trial-in-progress: Tarlatamab with durvalumab, carboplatin and etoposide versus durvalumab, carboplatin and etoposide as first-line (1L) therapy in extensive-stage small cell lung cancer (ES-SCLC) (Foyer) - Feb 5, 2026 - Abstract #ELCC2026ELCC_748;
P3
Key exclusion criteria are history of other malignancy within the past 2 years, active/documented autoimmune or inflammatory disorders, prior DLL3 pathway-selective inhibitor therapy, and prior history of severe/life-threatening events from any immune-mediated therapy. The dual primary endpoints are OS and PFS (by BICR), and secondary endpoints include PFS by investigator assessment, objective response, disease control rate, duration of response, safety, and tarlatamab pharmacokinetics.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
P4 data, Journal, Adverse events, Real-world evidence: Post-marketing safety surveillance of tarlatamab: a real-world pharmacovigilance study based on the FAERS database. (Pubmed Central) - Jan 29, 2026
Leveraging FAERS, this first comprehensive real-world characterization of tarlatamab safety confirms core immune-related toxicities (CRS, ICANS) and identifies new signals (TLS, respiratory failure), with sex- and age-associated risk differences. As spontaneous-report signals are inherently hypothesis-generating, causality requires validation in robust pharmacoepidemiologic studies; meanwhile, early detection and supportive care are essential to optimize the benefit-risk profile as use expands.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
FDA event, Journal: FDA Approval Summary: Tarlatamab for the Treatment of Extensive Stage Small Cell Lung Cancer. (Pubmed Central) - Jan 26, 2026
P2
The most common adverse reactions (?20%) were cytokine release syndrome (CRS), fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia and nausea. Product labeling includes a Boxed Warning for serious or life-threatening CRS and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen, Lorbrena (lorlatinib) / Pfizer
Journal: First Report of Response to Tarlatamab in a Patient With Histologic-Transformed SCLC From ALK-Rearranged NSCLC: Case Report. (Pubmed Central) - Jan 26, 2026
Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients. Here, we present a case of a patient with ALK-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Review, Journal, IO biomarker: Updates on Antibody Drug Conjugates and Bispecific T-Cell Engagers in SCLC. (Pubmed Central) - Jan 21, 2026
Collectively, these emerging immunotherapies illustrate a shift toward antigen-specific targeting in a disease historically defined by limited therapeutic innovation. Continued optimization of antigen selection, payload and linker engineering, and biomarker-driven trial design will be critical for translating early promise into durable clinical benefit and reshaping the treatment landscape for SCLC.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
Journal, Circulating tumor cells: Circulating Tumor Cells Predict Response to the DLL3-targeting Bispecific Antibody Tarlatamab. (Pubmed Central) - Jan 14, 2026
Acquired resistance to tarlatamab is associated in some cases with loss of DLL3 expression, but persistence of other targetable neuro-endocrine epitopes; in other patients, DLL3 is retained on CTCs, but accompanied by systemic markers of T cell dysfunction. Quantitation of DLL3-positive CTCs identifies patients likely to benefit from tarlatamab, and longitudinal monitoring may guide therapeutic decision-making at the time of acquired resistance.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
SCLC Outcomes and Real-World Insight with Tarlatamab, a Multi-Center Experience (Salon ABC) - Jan 14, 2026 - Abstract #IASLCTTLC2026IASLC_TTLC_178;
Conclusion Tarlatamab was overall well-tolerated in this real-world cohort and demonstrated preliminary efficacy for active CNS metastases. Real world efficacy appears similar to clinical trial results.
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