P2, N=16, Terminated, Rakuten Medical, Inc. | Active, not recruiting --> Terminated; Business decision

P2, N=22, Recruiting, Rakuten Medical, Inc. | Trial completion date: Sep 2025 --> Mar 2027

Our new antibody dye conjugate targeting EGFR-expressing bladder cancer cells is a promising candidate for the future PIT of bladder cancer patients.

We further demonstrate that these antibodies recognize the AREG neo-epitope in formalin-fixed, paraffin-embedded tumor tissue, suggesting their utility as a companion diagnostic for patient selection. This ADC targeting AREG has potential utility in the treatment of breast and other tumors in which proteolytic AREG shedding is a frequent event.

Furthermore, dual-targeted NIR-PIT showed antitumor immunity in distant untreated tumors of the same type. Thus, simultaneous cancer cell-targeted NIR-PIT and CTLA4-targeted NIR-PIT is a promising new cancer therapy strategy, especially in poorly immunogenic tumors where NIR-PIT monotherapy is suboptimal.

This method could also be applied to other types of cancer approachable with endoscopy. Supporting information.

Herein, we demonstrate noninvasive SWIR fluorescence imaging of human epidermal growth factor receptor 2 (HER2)-positive and epidermal growth factor receptor (EGFR)-positive breast tumors using π-conjugation extended ICG and monoclonal antibody conjugates. The presented π-conjugation extended ICG analog probes will be a breakthrough to apply SWIR fluorescence imaging in biomedical fields.

In September 2020, the Japanese government approved cetuximab saratolacan (previously known as RM-1929, commercial name: Akalux) for the treatment of unresectable locally advanced or recurrent head and neck cancer. The treatment consists in the intravenous injection of cetuximab saratolacan, which binds to head and neck cancer cells expressing high levels of EGFR, followed by illumination of the tumor with red light (690 nm) for photodynamic therapy. This approach causes immunogenic cell death in malignant tissues, thus triggering a potent anticancer immune response.

Background RM-1929 is an antibody-dye conjugate comprised of cetuximab covalently linked to the photoactivable dye, IRDye® 700DX (IR700). Conclusions These results suggest that rHNSCC patients with lower PD-L1 expression levels may be more responsive to RM-1929 treatment and CPS/TPS could potentially be predictive biomarkers in identifying patients with a higher probability of benefiting from this treatment. Given the limited number of patients in this analysis, additional clinical trials will be needed to validate PD-L1 expression as an effective predictive biomarker for RM-1929 treatment.

Background RM-1929 is an antibody-dye conjugate comprised of cetuximab covalently linked to the photoactivable dye, IRDye® 700DX (IR700). Conclusions These results suggest that rHNSCC patients with lower PD-L1 expression levels may be more responsive to RM-1929 treatment and CPS/TPS could potentially be predictive biomarkers in identifying patients with a higher probability of benefiting from this treatment. Given the limited number of patients in this analysis, additional clinical trials will be needed to validate PD-L1 expression as an effective predictive biomarker for RM-1929 treatment.

Finally, molecular docking analysis verified that the erlotinib moiety of compound CE17 could form hydrogen bond with Met-769 and occupy active cavity of EGFR-TK. Therefore, we believed the integration strategy between heptamethine cyanine dyes and EGFR-TKI will contribute to enhancing the therapeutic effect of EGFR-TKI for NSCLC treatment.

The ON-Cetuximab-treated mice expressed strong fluorescence throughout their body at 8 h post-injection; therefore, lung tumor sites could not be discriminated using fluorescence imaging. These results confirm the benefits of Q-Cetuximab for image-guided precision surgery of EGFR-positive lung cancers.