Inhibrx Biosciences, Inc. (Nasdaq: INBX) has announced encouraging preliminary efficacy and safety data from its Phase 1 trial of ozekibart (INBRX-109) in combination with FOLFIRI for patients with advanced or metastatic, unresectable colorectal adenocarcinoma (CRC). The data, presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Annual Cancers Symposium, suggest potential clinical benefits in heavily pretreated patients.
Efficacy and Disease Control
Efficacy was evaluated in 10 of the 13 patients who received at least one dose of ozekibart, based on RECIST v1.1 criteria. The results demonstrated a complete response (CR) in one patient, partial responses (PR) in three patients, and stable disease (SD) in six patients. Notably, 46.2% of patients achieved durable disease control lasting ≥180 days, with a median progression-free survival (PFS) of 7.85 months. All patients had received at least one prior line of systemic therapy, with a median of two prior lines (range: 1–6). The patient who achieved a CR had undergone three prior lines of therapy, and two PRs were observed in patients who had failed prior FOLFIRI-based treatments.
Safety Profile
Ozekibart-related treatment-emergent adverse events (TEAEs) were reported in 84.6% of patients, with the majority being grade 1 or 2 in severity. Grade ≥3 TEAEs were observed in 30.8% of patients. The most common ozekibart-related TEAEs included nausea, increased alanine aminotransferase, diarrhea, and fatigue, with most being low-grade.
Expansion Cohort and Future Directions
Based on these initial findings, Inhibrx has initiated a new expansion cohort to further evaluate ozekibart in a more uniform patient population. This cohort is expected to enroll up to 50 patients, each with two to three prior lines of systemic therapy, and data are anticipated in Q3 2025.
Josep Garcia, Chief Clinical Development Officer at Inhibrx, commented, "We believe these interim results underscore the potential of ozekibart to provide meaningful clinical benefit for patients with advanced solid tumors, even in heavily pretreated populations. We are particularly encouraged by the durable disease control observed and look forward to further evaluating these findings in our expansion cohort."
Colorectal Adenocarcinoma Context
Colorectal adenocarcinoma is a significant global health concern, ranking as the third most frequent cancer and the second leading cause of cancer-related deaths. The World Health Organization (WHO) reported nearly 2 million new cases of CRC in 2020, resulting in approximately 1 million deaths. Effective therapies beyond the second-line setting remain limited. In the U.S., the five-year relative survival rate for patients with metastatic CRC is 15.7%, highlighting the urgent need for improved treatment options.
About Ozekibart (INBRX-109)
Ozekibart is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to induce tumor-biased cell death through DR5 activation. The FDA has granted Fast Track designation to ozekibart for metastatic or unresectable conventional chondrosarcoma (January 2021) and orphan drug designation for chondrosarcoma (November 2021). In addition to the CRC trial, Inhibrx is also investigating ozekibart in a Phase 2 trial for chondrosarcoma and a Phase 1 trial for Ewing sarcoma.
