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DRUG CLASS:

CD56-targeted antibody-drug conjugate

5ms
Antibody-drug conjugates treatment of small cell lung cancer: advances in clinical research. (PubMed, Discov Oncol)
Although toxicities exceeding expectations have been observed with Rova-T, drugs targeting TROP-2 (Sacituzumab Govitecan), B7-H3 (DS-7300), and SEZ6 (ABBV-011) have shown exciting clinical benefits. In this review, we collect the latest clinical evidence to describe the therapeutic efficacy and safety of ADCs in SCLC and discuss prospects and challenges.
Review • Journal
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CD276 (CD276 Molecule) • DLL3 (Delta Like Canonical Notch Ligand 3) • NCAM1 (Neural cell adhesion molecule 1) • SEZ6 (Seizure Related 6 Homolog)
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Trodelvy (sacituzumab govitecan-hziy) • Rova-T (rovalpituzumab tesirine) • ifinatamab deruxtecan (DS-7300) • ABBV-011
8ms
Expression of Potential Antibody-Drug Conjugate Targets in Cervical Cancer. (PubMed, Cancers (Basel))
Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.
Journal
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FOLR1 ( Folate receptor alpha ) • MSLN (Mesothelin) • CEACAM5 (CEA Cell Adhesion Molecule 5) • DLL3 (Delta Like Canonical Notch Ligand 3) • CD70 (CD70 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1) • GPNMB (Glycoprotein Nmb) • TACSTD2 (Tumor Associated Calcium Signal Transducer 2)
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TROP2 expression • CD70 expression • SDC1 positive
almost2years
Surfaceome Profiling of Cell Lines and Patient-Derived Xenografts Confirm FGFR4, NCAM1, CD276, and Highlight AGRL2, JAM3, and L1CAM as Surface Targets for Rhabdomyosarcoma. (PubMed, Int J Mol Sci)
Ranking based on expression levels and comparison to expression in normal MRC-5 fibroblasts and myoblasts, followed by statistical analysis, highlighted known RMS targets such as FGFR4, NCAM1, and CD276/B7-H3, and revealed AGRL2, JAM3, MEGF10, GPC4, CADM2, as potential targets for immunotherapies of RMS. L1CAM expression was investigated in RMS tissues, and strong L1CAM expression was observed in more than 80% of alveolar RMS tumors, making it a practicable target for antibody-based therapies of alveolar RMS.
Preclinical • Journal • IO biomarker
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FGFR4 (Fibroblast growth factor receptor 4) • CD276 (CD276 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • AGR2 (Anterior gradient 2) • L1CAM (L1 cell adhesion molecule)
2years
Pediatric Acute Myeloid Leukemia with Co-Occurring BCR::ABL and CBFA2T3::GLIS2 Dual Fusion with Deep Response to FOLR1-Targeting Antibody Drug Conjugate Stro-002 and Tyrosine Kinase Inhibitor (ASH 2022)
Review of diagnostic genomic profile mid induction showed a BCR::ABL minor breakpoint fusion as well as CBF::GLIS fusion.The child began AML induction on COG AAML1831 trial randomized to the experimental arm with CPX-351 and gemtuzumab ozogamicin (GO). Due to lack of response to AML therapy at end of Induction (EOI) I, she was taken off protocol and started on modified ALL regimen for Induction II consisting of cytarabine, low dose weekly methotrexate and bimonthly peg-asparaginase with addition of an oral TKI, dasatinib...Given availability of FOLR1 directed ADC on single-patient compassionate use basis, patient received single agent STRO-001 on a bi-monthly basis...Long-term follow-up is required to assess durability of remission. Additional testing of this approach in a larger patient population is needed to determine the role of STRO-002 in this high-risk pediatric AML population.
Clinical • IO biomarker
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FOLR1 ( Folate receptor alpha ) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GLIS2 (GLIS Family Zinc Finger 2)
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FOLR1 expression • CD8 negative
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dasatinib • methotrexate • Mylotarg (gemtuzumab ozogamicin) • Vyxeos (cytarabine/daunorubicin liposomal formulation) • luveltamab tazevibulin (STRO-002) • bezetabart debotansine (STRO-001)
almost3years
Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. (PubMed, Lung Cancer)
Antibody-drug conjugates (ADCs) are rapidly establishing their place and have shown promising preliminary data in lung cancer with impressive response rates and survival outcomes in previously treated patients.There are several ADCs currently in clinical trials for NSCLC and small cell lung cancer (SCLC). These ADCs often have different targets which include HER2, HER3, TROP2, CEACAM5, and MET in NSCLC and DLL3 in SCLC.Here we review the safety, and efficacy of newer ADCs in lung cancer including ado-trastuzumab emtansine, trastuzumab deruxetecan, patritomab deruxetecan, datopotamab deruxetecan, sacituzumab govitecan, SAR408701, Telisotuzumab vedotin, rovalpituzumab tesirine, lorvotuzumab mertansine, and sacituzumab govitecan.  Several novel methods are underway to improve the safety and efficacy of ADCs which include increasing the drug to antibody ratio (DAR), the potency of the payload, using more innovative payloads and replacing the antibody.
Review • Journal
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HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CEACAM5 (CEA Cell Adhesion Molecule 5) • DLL3 (Delta Like Canonical Notch Ligand 3)
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Kadcyla (ado-trastuzumab emtansine) • Trodelvy (sacituzumab govitecan-hziy) • tusamitamab ravtansine (SAR408701) • telisotuzumab vedotin (ABBV-399) • Rova-T (rovalpituzumab tesirine) • lorvotuzumab mertansine (IMGN901)
almost3years
Clinical • Trial completion • Trial completion date
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NCAM1 (Neural cell adhesion molecule 1)
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NCAM1 expression
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lorvotuzumab mertansine (IMGN901)
3years
Journal
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NCAM1 (Neural cell adhesion molecule 1)
3years
Adcitmer , a new CD56-targeting MMAE-conjugated antibody is a potential therapeutic approach in Merkel cell carcinoma. (PubMed, Br J Dermatol)
Our study suggests Adcitmer® as a therapeutic option to be further assessed in MCC patients, as an alternative or combined with immune checkpoint inhibitors.
Journal • IO biomarker
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NCAM1 (Neural cell adhesion molecule 1)
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NCAM1 expression
over3years
[VIRTUAL] Adcitmer , a new CD56-targeting MMAE-conjugated antibody is a potential therapeutic approach in Merkel cell carcinoma (ESDR 2021)
Adcitmer significantly reduced tumor growth in a MCC mouse model. Our study suggests Adcitmer as a therapeutic option to be further assessed in MCC patients, as an alternative or combined with immune checkpoint inhibitors.
IO biomarker
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NCAM1 (Neural cell adhesion molecule 1)
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NCAM1 expression
4years
Bispecifics, trispecifics, and other novel immune treatments in myeloma. (PubMed, Hematology Am Soc Hematol Educ Program)
Belantamab mafodotin, a B-cell maturation antigen (BCMA)-targeted ADC, has shown response rates >30% in a phase 2 trial of highly refractory patients and is being investigated in a variety of settings and combinations...This is an area of active preclinical research at this time. Lastly, designed ankyrin repeat proteins, which are small antibody-mimetic proteins with high target-binding affinity, have the potential to block multiple pathways at once and provide stimulatory signals to the immune system.
Journal
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CD74 (CD74 Molecule) • CD38 (CD38 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1)
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Blenrep (belantamab mafodotin-blmf)
4years
[VIRTUAL] Pharmacokinetic and Pharmacodynamic Correlates from the Phase 1 Study of Camidanlumab Tesirine (Cami) in Patients with Relapsed or Refractory Hodgkin Lymphoma and Non-Hodgkin Lymphoma (ASH 2020)
While Treg modulation was seen with all populations, these data support further study, particularly of the Cami 45 µg/kg dose for pts with HL. Given that CD25 is the cognate target of Cami, these data suggest pts with HL achieving CR have higher drug exposure, resulting from lower baseline sCD25, and potential association with lower tumor burden. Although exposure at the 45 µg/kg dose showed moderate inter-patient variability, it was associated with noteworthy, cycle-related modulation in circulating Treg and clear increases in Teff:Treg ratios, thought to favor clinical response.
Clinical • P1 data • PK/PD data
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CD19 (CD19 Molecule) • CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2RA (Interleukin 2 receptor, alpha) • IL7R (Interleukin 7 Receptor) • NCAM1 (Neural cell adhesion molecule 1) • IL10 (Interleukin 10) • FOXP3 (Forkhead Box P3)
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IL2RA expression
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camidanlumab tesirine (ADCT-301)
4years
[VIRTUAL] Target-Informed Repurposing of Immunotherapies in AML – a Transcriptome Based Approach for Identifying Immediately Available Therapeutics (ASH 2020)
Future expansion of this methodology into other cellular therapies (CAR NK or BiTE) and the examination of new data sources could reveal additional targets with robust expression in AML. Demonstration of cell surface expression of these targets, and appropriate preclinical evidence of efficacy, could lay the groundwork for quickly moving these therapies to clinical trials in AML.
IO biomarker
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FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD74 (CD74 Molecule) • FOLR1 ( Folate receptor alpha ) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • MSLN (Mesothelin) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • CD44 (CD44 Molecule) • NCAM1 (Neural cell adhesion molecule 1)
over4years
Clinical • P2 data • Journal
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NCAM1 (Neural cell adhesion molecule 1)
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dexamethasone • lorvotuzumab mertansine (IMGN901)