CEACAM5-targeted antibody-drug conjugate News

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|||||||||| ATOR-4066 / Alligator Biosci
ATOR-4066, a Neo-X-Prime bispecific antibody targeting CD40 and CEACAM5, induces myeloid and T-cell dependent anti-tumor activity and synergizes with PD-1 inhibition (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_348;
Full Regular Abstract, Young Investigator Award (YIA), Immune Engineering Abstracts, and Late-breaking Abstract - Clinical Only (LBA) content will be embargoed until Nov. 5, 2024 at 8 a.m. CT / 9 a.m. ET

|||||||||| 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.

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi, AbbVie
Exploratory Analyses of Tusamitamab Ravtansine vs Docetaxel in Previously Treated Non-squamous NSCLC Patients: CARMEN-LC03 (Exhibit Hall) - Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_1559;
Conclusions : These exploratory analyses identify patients likely to derive clinical benefit from tusa rav and suggest a previously unknown prognostic role for CEACAM5 in NSCLC. Additional research is needed to corroborate these findings.

|||||||||| Tagrisso (osimertinib) / AstraZeneca
Analysis of Antibody-Drug Conjugate Target Expression Across Genomic Subsets of Non-Small Cell Lung Cancer (Exhibit Hall) - Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_1525;
We evaluated the ADC target expression in 9 paired pre- and post-osimertinib samples with EGFR mutations (exon 19 deletion, L858R, G719S/S768I, L861Q), finding no significant difference in the H-scores for MET [250 (100-291) vs 250 (0-300)], HER2 [0 (0-190) vs 3 (0-75)], TROP2 [130 (90-215) vs 115 (30-200)], CEACAM5 [40 (0-240) vs 60 (0-280)], and HER3 [0 (0-10) vs 0 (0-0)]...ADC target expression IHC H-scores in treatment-nai?ve NSCLC according to oncogene driver. H-score, Median (range) MET HER2 TROP2 CEACAM5 HER3 ALL (n=50) 220 (3-300) 15 (0-220) 152.5 (2-265) 137.5 (0-300) 0 (0-285) EGFR (n=16) 237.5 (100-295) 8.5 (0-220) 125 (5-230) 75 (0-295) 0 (0-285) ALK (n=10) 225 (160-300) 110 (15-160) 180 (137-220) 108 (0-295) 0 (0-8) ROS1 (n=9) 195 (59-290) 0 (0-170) 120 (15-210) 115 (0-210) 0 (0-0) RET (n=4) 242 (200-270) 52.5 (0-90) 90.5 (2-265) 126.5 (2-290) 3 (0-110) KRAS (n=11) 190 (2-300) 6 (0-150) 182.5 (30-205) 200 (0-300) 0 (0-10) Comparisons by oncogene driver EGFR vs KRAS p=0.183 p=0.421 p=0.635 p=0.288 p=0.305 EGFR vs fusion p=0.476 p=0.962 p=0.650 p=0.950 p=0.361 Fusion vs KRAS p=0.265 p=0.223 p=0.540 p=0.216 p=0.608 EGFR+fusion vs KRAS p=0.181 p=0.241 p=0.418 p=0.191 p=0.393

|||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Antibody-Drug Conjugates as Novel Therapeutic Agents for Non-Small Cell Lung Carcinoma with or without Alterations in Oncogenic Drivers. (Pubmed Central) - Jul 14, 2024
Several ADCs have already been approved for other cancers, such as breast cancer and urothelial carcinoma. 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.

|||||||||| 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.

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi, AbbVie
Assessment of carcinoembryonic antigen-related cell adhesion molecule 5 expression by immunohistochemistry in real-world clinical samples of non-small cell lung cancer. () - Apr 24, 2024 - Abstract #ASCO2024ASCO_6887;
The interrater reliability on the determination of high CEACAM5 expression was moderate among the three pathologists. We highlighted the challenging aspects in the evaluation of this biomarker.

|||||||||| M9140 / EMD Serono
First-in-human trial of M9140, an anti-CEACAM5 antibody drug conjugate (ADC) with exatecan payload, in patients (pts) with metastatic colorectal cancer (mCRC). (Hall D1) - Apr 24, 2024 - Abstract #ASCO2024ASCO_2163;
P1
Contrary to approved ADCs with Top1i payloads, no ILD or ocular toxicities were observed. Evaluation of M9140 in mCRC continues in the dose expansion part of this study.

|||||||||| PF-08046050 / Sanofi, Pfizer
An open-label phase 1 study to investigate SGNCEACAM5C/SAR445953 in adults with advanced solid tumors (SGNCEA5C-001). (Hall A; Poster Bd #: 305a) - Apr 24, 2024 - Abstract #ASCO2024ASCO_2131;
P1
5. Baudat 2024.

|||||||||| ATOR-4066 / Alligator Biosci
Modulation of the Tumour Microenvironment Using CD40 Targeting Neo-X-Prime bsAbs Developed Using the RUBY Format () - Apr 19, 2024 - Abstract #IOSUMMITEUROPE2024IO_SUMMIT_EUROPE_17;
The platform is built on bispecific antibodies targeting CD40 and highly expressed tumour-associated antigens (TAA). The lead candidate, ATOR-4066, targets CD40 and CEACAM5 and induces superior anti-tumour activity by myeloid cell-mediated and T cell-dependent mechanisms.

||||||||||  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,  Sponsor: EMD Serono Research & Development Institute, Inc.
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.

|||||||||| A novel epigenomic profiling assay reveals disease biology and therapeutic targets in gastro-esophageal cancer from 1 ml of plasma (Section 26) - Mar 5, 2024 - Abstract #AACR2024AACR_6859;
The HER2 classifier overcomes several of the challenges with IHC profiling by providing a uniform and quantitative measurement of HER2 activation. This non-invasive assay provides an accurate reflection of tumor transcriptional biology that can inform optimal patient selection strategies.

|||||||||| 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).

|||||||||| PF-08046050 / Sanofi, Pfizer
An open-label phase 1 study to investigate SGN-CEACAM5C in adults with advanced solid tumors (SGNCEA5C-001, Trial in Progress) (Section 49) - Mar 5, 2024 - Abstract #AACR2024AACR_3876;
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). Abstract is embargoed at this time.

|||||||||| BGB-B167 / BeiGene
BGB-B167, a first-in-class 4-1BB (CD137)/ CEACAM5 bispecific antibody, exhibits potent in vitro and in vivo anti-tumor activity and superior safety profile in preclinical models (Section 38) - Mar 5, 2024 - Abstract #AACR2024AACR_3764;
Here, we describe the characterization of BGB-B167 with regard to preclinical proof-of-concept and basic drug-like properties. The combined dataset provides an overview on the design, mode of action, preclinical pharmacology and safety profile of BGB-B167.

|||||||||| zosuquidar (LY335979) / Kanisa Pharma
Preclinical efficacy and safety of M9140, a novel antibody-drug conjugate (ADC) with topoisomerase 1 (TOP1) inhibitor payload targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5)?expressing colorectal tumors (Section 38) - Mar 5, 2024 - Abstract #AACR2024AACR_3755;
P1
The side effect profile in monkeys was favorable and in line with the expected toxicity of exatecan. Notably, ILD and ocular toxicity, which are known adverse effects of deruxtecan and maytansine-based ADCs respectively, were absent.

|||||||||| 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,  Sponsor: EMD Serono Research & Development Institute, Inc.
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

|||||||||| Preclinical, Journal: A novel human single-domain antibody-drug conjugate targeting CEACAM5 exhibits potent in vitro and in vivo antitumor activity. (Pubmed Central) - Feb 5, 2024
In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5?mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.

|||||||||| Preclinical, Journal, CAR T-Cell Therapy: New CEACAM-targeting 2A3 single-domain antibody-based chimeric antigen receptor T-cells produce anticancer effects in vitro and in vivo. (Pubmed Central) - Feb 1, 2024
Our results for the first time show an enhanced targeting toward CEACAM5 and CEACAM6 molecules by the new 2A3 sdAb-based CAR T-cells. The results strongly support the further development of 2A3-CAR T-cells as a potential treatment strategy against CEACAM5/6-overexpressing cancers.

|||||||||| CT109-ADC / Stromatis Pharma
Journal: CT109-SN-38, a Novel Antibody-drug Conjugate with Dual Specificity for CEACAM5 and 6, Elicits Potent Killing of Pancreatic Cancer Cells. (Pubmed Central) - Jan 5, 2024
The results strongly support the further development of 2A3-CAR T-cells as a potential treatment strategy against CEACAM5/6-overexpressing cancers. These data suggest that further preclinical and clinical development of CT109-SN-38 is warranted.

|||||||||| 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.

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi
Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker: The search for therapeutic targets in lung cancer: Preclinical and human studies of carcinoembryonic antigen-related cell adhesion molecule 5 expression and its associated molecular landscape. (Pubmed Central) - Sep 19, 2023
In NSQ-NSCLC tumors, CEACAM5 HE prevalence was 24.3% overall and was higher with KRAS altered and with PD-L1 negative/low tumors but similar regardless of EGFR mutation status. These findings support targeting CEACAM5 and the clinical development of tusamitamab ravtansine for patients with NSQ-NSCLC with CEACAM5 HE.

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi
P1 data, PK/PD data, Clinical Trial,Phase I, Journal, Metastases: Tusamitamab Ravtansine in Patients with Advanced Solid Tumors: Phase I Study of Safety, Pharmacokinetics, and Antitumor Activity Using Alternative Dosing Regimens. (Pubmed Central) - Sep 3, 2023
P1
(NCT02187848). The collective results of this phase I dose-escalation study will inform further studies of tusamitamab ravtansine in patients with solid tumors with CEACAM5 expression, including patients with non-small cell lung cancer.

|||||||||| TACSTD2 (Trop-2) constitutes a promising antibody-drug conjugate target for patients with non-small cell lung cancer brain metastases () - Jul 27, 2023 - Abstract #ESMO2023ESMO_2910;
Further validation is warranted in terms of protein expression. Our results underscore the potential value of gene expression profiling to identify new targets and improve patient selection in the context of NSCLC-BM ADC therapy.

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi, Cyramza (ramucirumab) / Eli Lilly
Tusamitamab ravtansine plus ramucirumab as 2L therapy or beyond in patients with metastatic NSq NSCLC and high CEACAM5 expression (CARMEN-LC04) () - Jul 27, 2023 - Abstract #ESMO2023ESMO_2903;
P2
Our results underscore the potential value of gene expression profiling to identify new targets and improve patient selection in the context of NSCLC-BM ADC therapy. Docetaxel

|||||||||| 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

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi
Phase 1/2 study of tusamitamab ravtansine in patients with advanced solid tumors: Pooled safety analysis of corneal adverse events. () - Apr 26, 2023 - Abstract #ASCO2023ASCO_4723;
P1
These results support the ongoing clinical development of tusa rav. Further investigation of the mechanisms of corneal TEAEs with ADCs and their management is necessary.

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi
Industry Expert Theater: Sanofi Oncology Pipeline and CEACAM5: A Potential Biomarker in Advanced Non-Small Cell Lung Cancer for Targeted Therapies (Available On Demand) - Apr 10, 2023 - Abstract #ASCO2023ASCO_746;
Sponsored by Sanofi. Join us for an overview of Sanofi

|||||||||| Dr. @Joshua_Reuss gives a great talk at #TexasLung23 on antibody drug conjugates including ADCs targeting #Trop2 #HER2 #HER3 #B7H7 #CEACAM5. Important class of agents, each with a unique target and set of toxicities. How will we use these in the future: combinations? 1L? (Twitter) - Apr 1, 2023

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi
Clinical: Tusamitamab ravtansine a humanized CEACAM5-specific antibody-drug conjugate linked to DM4, combined with SoC showed encouraging antitumor activity across all treatment arms. Some concerns regarding the safety profile (4 grade 5). @LuisPaz_Ares #ELCC23 (Twitter) - Mar 30, 2023

|||||||||| A novel topoisomerase I inhibitor antibody-drug conjugate targeting CEACAM5 has potent anti-tumor activity in colorectal cancer models (Section 14; Poster Board #1) - Mar 14, 2023 - Abstract #AACR2023AACR_7234;
The ADC induces a disease control rate of 95% and an overall response rate of 50% following a single dose of 10 mg/kg. The outstanding anti-tumor activity across CRC PDX models and its favorable safety profile in rats support further evaluation of this investigational novel topoisomerase I ADC in CRC patients.

|||||||||| NEO-201 / ImmunityBio
A therapeutic humanized anti-carcinoma monoclonal antibody (mAb) NEO-201 can also target human granulocytic myeloid-derived suppressor cells (gMDSCs) and regulatory T (Tregs) cells (Section 44; Poster Board #3) - Mar 14, 2023 - Abstract #AACR2023AACR_7042;
Depletion of suppressive Tregs and gMDSCs in the TME could be an effective strategy to prevent hyperprogressive disease when anti-PD-1 is used in cancer immunotherapy. These data support the rationale for the ongoing phase II clinical trial using NEO-201 in combination with pembrolizumab in checkpoint refractory patients with metastatic solid tumors.

|||||||||| Anti-CEACAM5 immune stimulant TLR7/8 agonist antibody drug conjugate is a potent myeloid cell activator for the treatment of CEACAM5-expressing tumors (Section 25; Poster Board #13) - Mar 14, 2023 - Abstract #AACR2023AACR_6305;
In a pharmacodynamic study using lung tumor patient-derived xenograft mouse model, this ADC triggers murine cytokine inductions, innate immune cell enrollment at tumor site, and tumor necrosis in a dose-dependent manner. Based on preclinical in vitro and in vivo data, the tusamitamab R848 ADC is an innovative ADC approach with the potential to eradicate CEACAM5+ tumors in patients.

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi
Biomarker analysis from Phase 1/2 study of tusamitamab ravtansine (SAR408701) in patients with advanced non-small cell lung cancer (NSCLC) (Section 47; Poster Board #3) - Mar 14, 2023 - Abstract #AACR2023AACR_6031;
P1
Based on preclinical in vitro and in vivo data, the tusamitamab R848 ADC is an innovative ADC approach with the potential to eradicate CEACAM5+ tumors in patients. In response evaluable CEACAM5 HEs with available BL cCEA data (n = 61), ORR was 10/24 (41.7%) in pts with high cCEA (?100

|||||||||| 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
Characterization of a novel immunohistochemistry (IHC) assay for CEACAM5 using a commercial antibody (Section 17; Poster Board #17) - Mar 14, 2023 - Abstract #AACR2023AACR_4933;
CI-P83-1 was the closest to 769 among the 5 clones. Further testing and validation are required to understand the finer differences between 769 and CI-P83-1.

|||||||||| tusamitamab ravtansine (SAR408701) / Sanofi
Biomarker analysis from Phase 1/2 study of tusamitamab ravtansine (SAR408701) in patients with advanced non-small cell lung cancer (NSCLC) (Exhibition and Poster area) - Feb 14, 2023 - Abstract #ELCC2023ELCC_377;
P1
Conclusions In CEACAM5 HEs, high cCEA was associated with numerically greater ORR vs low cCEA (41.7% vs 8.1%). Associations were also observed between: cCEA and cCEACAM5; IHC CEACAM5, cCEA, and cCEACAM5; and IHC CEACAM5 and CEACAM5 tumor mRNA levels, but not between IHC CEACAM5 and actionable oncogenic drivers.

|||||||||| 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.

|||||||||| Optimizing utilization of antibody-drug conjugates in NSCLC by identification of subsets using RNA sequencing (Hall Bordeaux) - Jan 31, 2023 - Abstract #ESMOTAT2023ESMO_TAT_127;
Particularly, CEACAM5 and TACSTD2 expression showed an inverse correlation and appeared to be nearly mutually exclusive biomarkers. This emphasizes the need for biomarker-based approaches for optimal selection of ADCs based on expression of target antigens.



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