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  • Positive associations of ac...
    Ou, Chien-Chih; Tsao, Chun-Yen; Yu, Chung-Yun; Yang, Cheuh-hao; Tang, Wei-Chien; Yang, Ming-Chen; Ho, Ching-Liang; Lai, Ming-Tain

    Journal of clinical oncology, 06/2024, Letnik: 42, Številka: 16_suppl
    Journal Article

    e14671 Background: OBI-833/OBI-821 (OBI-833) is a novel active immune therapy (cancer vaccine) targeting a tumor-associated carbohydrate antigen, Globo H. Previous reports have shown that OBI-833 can elicit a beneficial immune response in Non-Small Cell Lung Cancer (NSCLC) patients and rendered durable stable disease with some TKI-treated patients. In this study, we further evaluated the effect of OBI-833-induced immune responses on the in-study progression-free survivals (isPFS) during the treatment. Methods: Sera were collected for the evaluations of maximum concentration (Cmax) and exposure (area under the curve: AUC) of anti-Globo H IgM (GH IgM) and IgG (GH IgG), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and ex-vivo GH IgM induction with PBMC from each subject at baseline. The correlations of OBI-833-induced immune responses with isPFS and best overall response (BOR) were also evaluated. Pearson correlation coefficient analysis was used for all correlation evaluations. Results: Among the 14 OBI-833-treated subjects, 93% and 64% of subjects had significant increase in GH IgM and GH IgG, respectively. Median Cmax GH IgM and Cmax GH IgG were 13.8 µg/mL and 12.4 µg/mL, respectively. While the increase in CDC activities was not significantly correlated with the increase of GH IgM, a weak association between GH IgG and ADCC was observed (r=0.3380, p<0.0001). In addition, a strong association (r=0.84) was observed between Ex-vivo IFN-γ secreting and their Cmax IgM concentration in the OBI-833 Ex-vivo stimulation study. In contrast, weak association (r=0.26) was observed between Ex-vivo GH IgM induction and their Cmax of IgM. Correlations of the immune responses on isPFS were further analyzed. Significant positive correlations were observed for the Cmax and AUC of GH IgM with isPFS (Cmax: r=0.6345, p=0.0148; AUC: r=0.8212, p=0.0003) and the Cmax and AUC of GH IgG with isPFS (Cmax: r=0.7192, p=0.0037; AUC: r=0.6306, p=0.0062). Furthermore, distinct features of GH IgG responses from 2 subjects were identified based on the ADCC-GH IgG scatter plot. Samples from subject 034-006 showed high ADCC activity with relatively low GH IgG concentration, whereas the BOR was at -27%, which has significant negative correlation of tumor response (TR) with GH IgG (r=-0.7381, p=0.0148) and ADCC (r=-0.8565, p=0.0016). In contrast, samples from subject 034-004 showed average ADCC activity and relatively high GH IgG concentration with BOR at -12%, showing a negative correlation of TR with GH IgG (r=-0.8352, p=0.0001) and ADCC (r=-0.5690, p=0.0269). Conclusions: OBI-833 can elicit beneficial immune responses in NSCLC patients. Both GH IgM and GH IgG may contribute to the isPFS and TR of the subjects. Further development of OBI-833 in EGFR-mutated NSCLC patients phase II trial is ongoing.