- |||||||||| Vyloy (zolbetuximab) / Astellas, bemarituzumab (AMG 552) / Amgen
Review, Journal: New therapeutic target molecules for gastric and gastroesophageal junction cancer. (Pubmed Central) - Aug 26, 2024 Phase III and Ib/III trials of the FGFR2-targeted antibody bemarituzumab for G/GEJ cancer overexpressing FGFR2b are ongoing based on the promising result in a phase II trial, especially in cases with an FGFR2b positivity of???10%...CLDN18.2 is expressed in some G/GEJ tumors but lacks oncogenic driver potential, and the CLDN18.2-targeted antibody zolbetuximab prolonged the survival of CLDN18.2-positive G/GEJ cancer patients in phase III trials...Similarly, targeting of nondriver molecules such as DKK1, TROP2, and CEACAM5 is under investigation in early-stage clinical trials. This shift in focus from target molecules with driver potential to markers for precise drug delivery should increase the number of possible targets in G/GEJ cancer.
- |||||||||| labetuzumab govitecan (IMMU-130) / Gilead
Journal: CEACAM5-Targeted Immuno-PET in Androgen Receptor-Negative Prostate Cancer. (Pubmed Central) - Jul 1, 2024 This review summarizes the knowledge about the efficacy and tolerance profiles of ADCs targeting TROP2, HER2, HER3, CEACAM5 and c-MET in metastatic NSCLC with and without alterations in oncogenic drivers. [89Zr]Zr-DFO-labetuzumab imaging was able to clearly delineate both neuroendocrine H660 xenografts and AR- DU145 in
- |||||||||| Journal: Camelid-derived Tcell engagers harnessing human ?? T (Pubmed Central) - May 28, 2024
[89Zr]Zr-DFO-labetuzumab imaging was able to clearly delineate both neuroendocrine H660 xenografts and AR- DU145 in Furthermore, restricting the activation of fresh human peripheral T
- |||||||||| Journal: Expression of Potential Antibody-Drug Conjugate Targets in Cervical Cancer. (Pubmed Central) - May 11, 2024
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.
- |||||||||| M9140 / EMD Serono
Trial completion date, Trial primary completion date, Metastases: Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (PROCEADE-CRC-01) (clinicaltrials.gov) - Mar 27, 2024 P1, N=180, Recruiting, The lead candidate, ATOR-4066, targets CD40 and CEACAM5 and induces superior anti-tumour activity by myeloid cell-mediated and T cell-dependent mechanisms. Trial completion date: May 2025 --> Feb 2026 | Trial primary completion date: Apr 2024 --> Feb 2026
- |||||||||| P329G-Engager: A novel universal antibody-based adaptor platform for cancer immunotherapy (Section 3) - Mar 5, 2024 - Abstract #AACR2024AACR_9493;
Neither the individual P329G IgG nor the individual P329G-TCB induced anti-tumoral efficacy, validating the requirement for primary and secondary antibody binding for T cell engaging activity.These results provide in vitro and in vivo evidence that the universal P329G engager platform can be used as an efficacious cancer treatment. Ultimately, this modular approach may enable off-the-shelf personalization via combination of patient-specific antibodies and universal effector cell engagers based on the patient's tumor target and immune profile.
- |||||||||| ATOR-4066 / Alligator Biosci
ATOR-4066, a Neo-X-Prime (Section 3) - Mar 5, 2024 - Abstract #AACR2024AACR_8283; In contrast, RNA-sequencing of peripheral blood in ATOR-4066 treated mice showed only small transcriptomic differences compared to the vehicle treated group, but distinct from mice treated with a CD40 mAb, further demonstrating the CEACAM5 dependent response of ATOR-4066. In summary, these preclinical data demonstrate that ATOR-4066 activates infiltrating myeloid cells resulting in increases in activated tumor infiltrating T cells, thus creating a pro-inflammatory tumor microenvironment, which strongly supports further development and clinical testing of ATOR-4066.
- |||||||||| tusamitamab ravtansine (SAR408701) / Sanofi, AbbVie
Tusamitamab ravtansine induces immunogenic cell death and synergizes with anti-PD-1 or anti-PD-L1 antibody combination in solid tumor (Section 43) - Mar 5, 2024 - Abstract #AACR2024AACR_5138; In this model, the combination of tusamitamab ravtansine with anti-PD-1 or anti-PD-L1 antibody led to complete response and, even, tumor-free survivors at 120 days post tumor implantation while single agents were inactive or transiently active. In summary, these preclinical data show that tusamitamab ravtansine could be beneficially combined with immune checkpoint and strongly support their evaluation in clinical development.
- |||||||||| PF-08046050 / Sanofi, Pfizer
SGN-CEACAM5C / SAR445953, a novel topoisomerase I inhibitor antibody-drug conjugate targeting CEACAM5, has potent anti-tumor activity in CRC, PDAC, GC and lung cancer tumor models (Section 30) - Mar 5, 2024 - Abstract #AACR2024AACR_4068; P1 In CRC, gastric and lung cancer SMT, disease control rates are 95%, 84% and 87%, respectively with overall response rates of 55%, 68% and 71% including 15%, 10% and 26% of complete responses, respectively. The high anti-tumor activity across panels of PDX models of several CEACAM5 positive indications supports further evaluation of SGN-CEACAM5C / SAR445953 in patients with CRC, PDAC, GC and lung cancers (NCT06131840).
- |||||||||| Recentin (cediranib) / AstraZeneca, Avastin (bevacizumab) / Roche
Targeted proteomics and next-generation sequencing (NGS) for biomarker discovery in metastatic colorectal cancer (mCRC) (Section 39) - Mar 5, 2024 - Abstract #AACR2024AACR_2474; P2/3 Our preliminary findings for this cohort indicate the benefit of the use of multi-modal methodologies to inform better strategies for patient stratification and precision medicine, though further assessment of proteogenomic characteristics is needed. This data may inform future clinical development and guide patient eligibility to clinical trials and possible treatment sequencing for ADCs.
- |||||||||| M9140 / EMD Serono
Enrollment change, Trial completion date, Trial primary completion date, Metastases: Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (PROCEADE-CRC-01) (clinicaltrials.gov) - Mar 3, 2024 P1, N=180, Recruiting, This data may inform future clinical development and guide patient eligibility to clinical trials and possible treatment sequencing for ADCs. N=31 --> 180 | Trial completion date: Nov 2023 --> May 2025 | Trial primary completion date: Nov 2023 --> Apr 2024
- |||||||||| Journal: Generation and Characterization of Iduronidase-Cleavable ADCs. (Pubmed Central) - Dec 6, 2023
Finally, in vivo antitumor activity could be demonstrated for an IduA-cleavable duocarmycin ADC. The presented results emphasize the potential of iduronide linkers for ADC development and represent a tool for further balancing out tumor selectivity and safety.
- |||||||||| SCS-03: How CEACAM5 Expression Can Be Measured and Leveraged in NSCLC Care: Current Developments & Future Therapeutic Opportunities (Chicago Ballroom ABCD) - Nov 29, 2023 - Abstract #IASLCNACLC2023IASLC_NACLC_93;
The presented results emphasize the potential of iduronide linkers for ADC development and represent a tool for further balancing out tumor selectivity and safety. Promising initial evidence demonstrates the potential of targeting CEACAM5 to provide additional therapeutic options for patients with lung cancer, and several ongoing clinical trials are evaluating CEACAM5-targeting agents across different settings in NSCLC.In this live satellite symposium, renowned experts will discuss the clinical rationale for targeting CEACAM5, explore how strategies to test for CEACAM5 fit into larger testing paradigms in NSCLC, and review ongoing research efforts to develop antibody-drug conjugates
- |||||||||| ifinatamab deruxtecan (DS-7300) / Daiichi Sankyo, Merck (MSD), Trodelvy (sacituzumab govitecan-hziy) / Everest Medicines, Gilead, Rova-T (rovalpituzumab tesirine) / AbbVie
Review, Journal: Unlocking New Horizons in Small-Cell Lung Cancer Treatment: The Onset of Antibody-Drug Conjugates. (Pubmed Central) - Nov 25, 2023 Furthermore, an anti-B7-H3 (CD276), ifinatamab deruxtecan (DS7300A), showed a high response rate and durable responses in heavily pretreated SCLC...Further studies are needed to determine their efficacy and safety and the best location in the treatment algorithm for SCLC. In this review, we aim to collect and describe the results regarding the past, the present, and the future of ADCs in SCLC.
- |||||||||| ATOR-4066 / Alligator Biosci
Combination treatment with ATOR-4066, a Neo-X-Prime (Exhibit Hall B) - Sep 27, 2023 - Abstract #SITC2023SITC_1164; Furthermore, using DTCs from gastric cancer patients, ATOR-4066 induced activation of multiple immune cell populations. Conclusions Overall, these data emphasize the potential of ATOR-4066 as monotherapy and as a checkpoint inhibitor combination partner to further enhance the immune response in tumors, demonstrating the promise of this new candidate drug for further clinical development.
- |||||||||| Review, Journal, IO biomarker: Antibody-Drug Conjugates in Lung Cancer: Recent Advances and Implementing Strategies. (Pubmed Central) - Jul 19, 2023
In this review, we discuss the available evidence and future perspectives on ADCs for lung cancer treatment, including a comprehensive discussion on structure-based drug design, mechanism of action, and resistance concepts. Data were summarized by specific target antigen, biology, efficacy, and safety, differing among ADCs according to the ADC payload and their pharmacokinetics and pharmacodynamics properties.
- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca
Antibody-Drug Conjugates for Lung Cancer: Payloads and Progress () - Jun 1, 2023 - Abstract #ASCO2023ASCO_7174; Trastuzumab Deruxtecan (also known as DS-8201a or T-DXd) an ADC directed at HER2 recently became the first ADC to receive FDA approval in lung cancer, on the basis of its activity in tumors with HER2 mutations, demonstrated in the Destiny-Lung01 and Lung02 trials. PRACTICAL APPLICATIONS: Traztuzumab deruxtecan (T-DXd) is the first antibody-drug conjugate (ADC) approved for lung cancer on the basis of activity in patients with HER2 mutation
- |||||||||| MODULE 6: Future Directions in the Management of Metastatic NSCLC (Hilton Chicago, Grand Ballroom ) - May 15, 2023 - Abstract #ASCO2023ASCO_7042;
This event is organized and accredited by Research to Practice and supported through educational grants provided by AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Lilly, Novocure Inc, Regeneron Pharmaceuticals Inc, and Takeda Pharmaceuticals USA Inc. Biologic rationale for targeting TROP2 in lung cancer; mechanism of action of the TROP2-directed antibody-drug conjugate datopotamab deruxtecan (dato-DXd) Clinical activity observed with dato-DXd as monotherapy and in combination with other systemic anticancer therapies for advanced NSCLC; ongoing Phase III studies Incidence and severity of toxicities associated with dato-DXd, including interstitial lung disease Mechanism of action of tumor treating fields; preclinical and early clinical data supporting the investigation of this treatment modality in NSCLC Emerging positive results from the Phase III LUNAR study of tumor treating fields concurrent with immune checkpoint inhibition or docetaxel for metastatic NSCLC after failure of platinum-based therapy Potential clinical role of tumor treating fields in the care of patients with progressive NSCLC Early-phase data with anti-PD-1/PD-L1 antibodies in combination with other systemic therapies (eg, ramucirumab/pembrolizumab, lenvatinib/pembrolizumab, sitravatinib/nivolumab, durvalumab/ceralasertib) for progressive advanced NSCLC Other promising novel agents and strategies in clinical development for advanced NSCLC
- |||||||||| 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.
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