CEACAM5 overexpression

The comprehensive list of CEA-positive human tumor types demonstrates that CEA is expressed in a broad range of epithelial neoplasms, many of which might benefit from CEA serum monitoring and anti-CEA therapies.

Collectively, our findings identified firstly that SARS-CoV-2 spike induced intestinal barrier dysfunction through the interaction between CEACAM5 and Galectin-9. The result provides potential therapeutic targets in intestinal barrier dysfunction for treating severe COVID patients.

P1/2, N=80, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jul 2025 --> Dec 2024 | Trial primary completion date: Jul 2025 --> Dec 2024

P1, N=9, Recruiting, China Medical University, China | Not yet recruiting --> Recruiting

P1/2, N=80, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1, N=9, Not yet recruiting, China Medical University, China

Docetaxel ± ramucirumab (ram) every 3 weeks is standard second-line therapy for mNSQ NSCLC without targetable mutations after progression on immunotherapy ± chemotherapy. Conclusions Tusa rav + ram showed encouraging efficacy. The safety of this combination was consistent with the safety profile of each drug, with no unexpected safety signals.

[68 Ga]Ga-HNI01 is a novel CEA-targeted PET imaging radiotracer with excellent pharmacokinetics and favorable dosimetry profiles. [68 Ga]Ga-HNI01 PET is an effective and convenient imaging tool for detecting CRC lesions, particularly for identifying small metastases. Furthermore, its high specificity for CEA in vivo makes it an ideal tool for selecting patients for anti-CEA therapy.

Thus, the therapeutic effect of CAR-T therapy was related to the target antigen expression level, and the further retrospective analysis of pathological findings from PDAC patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. Therefore, CEA expression levels in biopsies or surgical specimens can be clinically used as biomarkers to select PDAC patients for anti-CAR-T therapy.

6 Tempus xT-Onco reliably detects HLA LOH and quantifies CEA and MSLN expression. Based on these data, patients with solid tumors are now being prospectively screened for HLA LOH using xT-Onco in an ongoing tissue banking study (BASECAMP-1, NCT04981119 ), preparing for future interventional protocols.

P1/2, N=80, Recruiting, Hoffmann-La Roche | Trial completion date: Oct 2024 --> Jul 2025 | Trial primary completion date: Oct 2024 --> Jul 2025

Corneal toxicity was manageable with dose delay or modification. Conclusions Tusamitamab ravtansine was well tolerated in patients with CRC or GC.

The outcomes of this research suggest that miR-498 is capable of repressing the proliferation, migration, and EMT of GC cells through CEACAM5 downregulation.

A Phase 3 study (NCT04154956) is currently ongoing in previously treated patients with NSQ NSCLC and high CEACAM5 expression comparing tusamitamab ravtansine to docetaxel. The study is designed to determine whether a broader patient population can benefit from treatment with tusamitamab ravtansine, compared with the patient population in the ongoing phase 3 study. Clinical Trials.gov identifier: NCT05245071.

The limit of detection for CEA in PBS and serum is calculated from a linear regression graph to be 0.5 ng/mL with R values of 0.9593 and 0.9657, respectively, over a linear range from 0.5 to 500 ng/mL. This CEA quantification by the aptasensor can help diagnose various surgical tumors and monitor their progression.

Almost half (47%) of pts who achieved a PR were treated for ≥ 1 y, suggesting that response to tusa in heavily pretreated pts was durable and frequently sustained. No patient discontinued long-term treatment because of drug-related toxicity. Corneal toxicity in these pts was manageable with dose modification (delay/reduction).

Xenografts subjected to targeted drug-loaded cubosomes showed a 5-7-fold higher drug accumulation in the tumor tissue compared to the liver, kidneys, and other vital organs, a significant decrease in tumor growth, and an increased survival rate compared to the nontargeted group. This work encompasses the first thorough preclinical investigation of Affimer targeted cubosomes as a cancer therapeutic.

The primary objective is to assess tolerability and determine the recommended dose in the combinations in Parts A, B, and C. Key secondary objectives are safety/tolerability, antitumor activity (objective response rate), pharmacokinetics, and immunogenicity. As of Jan 5, 2022, 27 sites in 7 countries are recruiting.

Due to high tumor specificity, CEA-regulated OA therapy has demonstrated a surprising antitumor effect for common CEA-positive tumors in preclinical trials These data suggested that CEA could be a diagnostic and prognostic biomarker for several rare solid tumors. We proposed the hypothesis that CEA-regulated oncolytic virus therapy could be a promising therapeutic strategy for CEA-positive rare solid tumors.

The micro-single photon emission computed tomography (micro-SPECT) imaging of [ Tc]Tc-scFv-96NRT showed a specific accumulation pattern, as blocking experiment with excess scFv-96NRT suppressed the tumor uptake. These preliminary results suggest that [ Tc]Tc-scFv-96NRT is a potential non-invasive molecular probe for imaging tumors with CEA over-expression.

P1/2, N=80, Recruiting, Hoffmann-La Roche | Trial completion date: Jun 2024 --> Oct 2024 | Initiation date: Apr 2021 --> Jul 2021 | Trial primary completion date: Jun 2024 --> Oct 2024

Almost 20% of prescreened NSCLC pts had high CEACAM5 expression. High CEACAM5 expressors exhibited a mixed pattern of whole membrane and polarized staining, with a predominance of whole membrane expression. In CEACAM5 moderate expressors, whole membrane CEACAM5 expression was similar to polarized CEACAM5 expression.

Background: In patients with metastatic non-small cell lung cancer (NSCLC) lacking targetable mutations who progress on immunotherapy and platinum-based chemotherapy, treatment options are generally limited to docetaxel ± a VEGF inhibitor such as ramucirumab. Parts 1 and 2 secondary endpoints include: safety, duration of response, progression-free survival, pharmacokinetics of tusa and ramucirumab, and anti-therapeutic antibodies. This study is recruiting participants at 12 sites in 6 countries, and has reached part 2 at all sites.

High CEACAM5 expression in colorectal cancer cells is firmly associated with the CD133-positive colorectal CSC phenotype, but it is unlikely that CD133 directly regulates CEACAM5 expression.

P1/2, N=80, Recruiting, Hoffmann-La Roche

P1; N=26; Terminated; Sponsor: Hoffmann-La Roche; Completed --> Terminated; Study terminated due to change in benefit-risk ratio, driven by high incidence GI toxicity in absence of clinically significant anti-tumor efficacy.

P1, N=26, Completed, Hoffmann-La Roche | Terminated --> Completed

P1, N=26, Terminated, Hoffmann-La Roche | N=150 --> 26 | Trial completion date: Dec 2020 --> Jul 2019 | Recruiting --> Terminated | Trial primary completion date: Dec 2020 --> Jul 2019; Study terminated due to change in benefit-risk ratio, driven by high incidence GI toxicity in absence of clinically significant anti-tumor efficacy.

P1, N=150, Recruiting, Hoffmann-La Roche | Trial completion date: Jun 2021 --> Dec 2020

P1, N=150, Recruiting, Hoffmann-La Roche | Trial completion date: Apr 2020 --> Jun 2021 | Trial primary completion date: Oct 2019 --> Dec 2020