CEACAM5-targeted antibody-drug conjugate 
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  • ||||||||||  Tumor-specific CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors (Section 24; Poster Board #30) -  Mar 14, 2023 - Abstract #AACR2023AACR_5142;    
    CD28 bispecifics were identified with selective potency on high versus low expressing cell lines, suggesting a favorable therapeutic index. CD28 bispecific antibodies co-targeting CEACAM5, Trop-2, STEAP1, and mesothelin show promising activity and warrant further development across a range of solid tumors.
  • ||||||||||  tusamitamab ravtansine (SAR408701) / Sanofi, Keytruda (pembrolizumab) / Merck (MSD)
    Safety and efficacy of tusamitamab ravtansine in combination with pembrolizumab  (Auditorium 4) -  Feb 10, 2023 - Abstract #ELCC2023ELCC_310;    
    P2
    Objective response rate (ORR) and disease control rate (DCR) for all patients were 40% and 88%, respectively. Table: 13MO Conclusions Tusa rav combined with SoC showed encouraging antitumor activity across all treatment arms with a favorable safety profile, including in the T4 arm, and no new safety concerns, supporting ongoing evaluation of tusa rav.
  • ||||||||||  Journal:  Antibody Drug Conjugates in Lung Cancer. (Pubmed Central) -  Nov 18, 2022   
    Currently, early-phase trials of ADCs in non-small cell lung cancer are rapidly gaining ground, with promising results targeting HER2 (human epidermal growth factor 2), HER3, TROP2 (trophoblast cell surface antigen 2), MET, CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5), and PTK7 (tyrosine protein kinase-like 7). Unfortunately, in small cell lung cancer, trials targeting the ubiquitous DLL3 (delta-like ligand 3) protein have failed to show clinically relevant results, despite significant toxicity.
  • ||||||||||  Development of a novel antibody-drug conjugate targeting both CEACAM5 and CEACAM6 (Exhibition Hall) -  Sep 3, 2022 - Abstract #AACRNCIEORTC2022AACR_NCI_EORTC_377;    
    CT109-SN-38 similarly exhibits a dose-dependent effect in reducing tumor growth in a heterotopic PDAC tumor xenograft model, with 2/10 mice exhibiting tumor regression throughout the study. Further preclinical and clinical development of CT109-SN-38 is warranted.
  • ||||||||||  Review, Journal:  Antibody drug conjugates in non-small cell lung cancer: An emerging therapeutic approach. (Pubmed Central) -  Jan 27, 2022   
    We also summarize the clinical development of several promising ADCs in early phase clinical trials for the treatment NSCLC. including ADCs against well-established targets (e.g.HER2 in breast cancer, Nectin4 in urothelial cancer), novel antigenic targets (e.g. HER3, TROP2, PTK7, CEACAM5), as well as promising combinations with agents known to be active in NSCLC such as tyrosine kinase inhibitors and ICI therapy, as a strategy to overcome mechanisms of resistance to ADC therapy.
  • ||||||||||  Review, Journal:  Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. (Pubmed Central) -  Jan 27, 2022   
    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.
  • ||||||||||  labetuzumab govitecan (IMMU-130) / Gilead
    Clinical, Journal:  Regulation of CEACAM5 and therapeutic efficacy of an anti-CEACAM5-SN38 antibody-drug conjugate in neuroendocrine prostate cancer. (Pubmed Central) -  Jan 19, 2022   
    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. Our findings provide insights into the scope and regulation of CEACAM5 expression in prostate cancer and strong support for clinical studies of labetuzumab govitecan for NEPC.
  • ||||||||||  docetaxel / Generic mfg.
    [VIRTUAL] Antibody Drug Conjugates for Non - small Cell Lung Cancer (Program Auditorium) -  Jun 17, 2021 - Abstract #IASLCWCLC2021IASLC_WCLC_33;    
    Datopotamab-DXd (Dato-DXd), other Trop2-ADC, showed promising efficacy and feasibility in phase I trial for advanced NSCLC, despite of relatively high frequency of ILD (14/175, 8%, including 3 G5) (8)...CEACAM5, also know as CEA, is detected in adenocarcinoma NSCLC(9) and CEACAM5-DM4 (SAR408701) is CEACAM5 targeted ADC, which preliminary efficacy and safety of phase I trial has been reported (10)...Telisotuzumab-vedotin (Teliso-V) is an anti–c-Met ADC of the telisotuzumab conjugated to the MMAE...From those promising results, phase 3 trial comparing with docetaxel for c-MET expressing patients is ongoing...Presented at the American Association for Cancer Research Annual Meeting 2021; April 10-15, 2021; Virtual. CT179.
  • ||||||||||  [VIRTUAL] Differential expression of surface protein-encoding genes highlights therapeutic vulnerabilities of four SCLC subtypes (virtual poster hall) -  Nov 3, 2020 - Abstract #SITC2020SITC_2132;    
    The two non-neuroendocrine subtypes, SCLC-P and SCLC-I shared some common hits such as the NK cell ligand MICA and B7H6. All of the identified and highlighted hits have been or are actively being pursued in clinical trials, highlighting the importance of understanding their expression levels pre- and post-treatment so that novel therapies can be developed that will be effective over the course of disease progression Conclusions The underlying biology defining our four identified subtypes of SCLC has revealed a striking number of targetable, differentially expressed surface protein encoding genes many of which already have clinically available reagents that could be repurposed for treatment of SCLC on a subtype-specific basis.
  • ||||||||||  [VIRTUAL] Differential expression of surface protein-encoding genes highlights therapeutic vulnerabilities of four SCLC subtypes (virtual poster hall) -  Nov 3, 2020 - Abstract #SITC2020SITC_2012;    
    The two non-neuroendocrine subtypes, SCLC-P and SCLC-I shared some common hits such as the NK cell ligand MICA and B7H6. All of the identified and highlighted hits have been or are actively being pursued in clinical trials, highlighting the importance of understanding their expression levels pre- and post-treatment so that novel therapies can be developed that will be effective over the course of disease progression Conclusions The underlying biology defining our four identified subtypes of SCLC has revealed a striking number of targetable, differentially expressed surface protein encoding genes many of which already have clinically available reagents that could be repurposed for treatment of SCLC on a subtype-specific basis.