71MO - OBI-833 was safe and immunogenic, without treatment-related SAEs, in a phase I dose-escalation trial

Background

OBI-833, a novel cancer active immunotherapy, consists of a synthetic Globo H combining with a recombinant CRM 197. Globo H is a tumor-associated carbohydrate antigen found in many epithelial cancers. A phase I trial assessed the safety and immune response of OBI-833 in subjects with advanced/metastatic gastric, lung, colorectal or breast cancer.

Methods

Subjects who failed to respond to at least one line of anticancer therapy were enrolled. For lung or breast cancer patients receiving targeted or hormone therapy, OBI-833 was added to their therapeutic regimen. Patients received a total of 10 subcutaneous injections of OBI-833/OBI-821. Three escalated doses of 10 μg, 30 μg, and 100 μg of OBI-833 were studied. A standard 3+3 rule was applied for dose escalation and DLT assessment.

Results

Eleven patients were enrolled, and all patients are now off study treatment. These patients include one lung cancer, seven colorectal cancer and three breast cancer patients. No patients in any of the three cohorts developed a DLT. The most common treatment-related AE was grade 1–2 injection site reaction, including erythema, induration, soreness, pruritus, etc. occurring on the day of injection and recovering within 2–3 days without requiring further medical treatment. Five treatment-unrelated SAEs were reported, including acute respiratory failure leading to death, bilateral malignant pleural effusion associated with disease progression, death associated with disease progression, hyponatremia, and acute kidney injury, which were all related to their underlying disease. All three doses of OBI-833/OBI-821 elicited anti-Globo H IgM and IgG antibody response, at least once during the course of therapy. Only one patient with NSCLC had a robust anti-Globo H IgG response. A positive correlation between complement-dependent cytotoxicity activities at a given time point and the anti-Globo H IgM level was observed. However, only minimum anti-Globo H IgG level and antibody-dependent cell-mediated cytotoxicity activity were detected.

Conclusions

OBI-833/OBI-821 had a favorable safety profile and generated detectable anti-Globo H IgM/IgG responses. The 30 μg dose of OBI-833 and NSCLC cancer type were selected for the cohort expansion.

Clinical trial identification

NCT02310464.

Editorial acknowledgement

Legal entity responsible for the study

OBI Pharma.

Funding

OBI Pharma.

Disclosure

C-C. Ou: Full/Part-time employment: OBI Pharma. Y. Yen: Advisory/Consultancy: OBI Pharma. All other authors have declared no conflicts of interest.