FDA accepted Inhibrx’s BLA for ozekibart in unresectable or metastatic chondrosarcoma; Phase 3 trial doubled PFS vs placebo, with PDUFA date set for April 2027.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has accepted for filing Inhibrx Biosciences’ Biologics License Application (BLA) for ozekibart (INBRX-109) in patients with unresectable or metastatic conventional chondrosarcoma.
The agency identified no filing review issues and assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 14, 2027.
The submission is supported by positive results from the registrational Phase 3 ChonDRAgon trial, where ozekibart significantly improved progression-free survival (PFS) compared with placebo. If approved, the therapy would become the first FDA-approved systemic treatment for patients with advanced conventional chondrosarcoma, a disease with no established drug therapies.
Targeting a Major Unmet Need in Bone Cancer
Chondrosarcoma is the second most common primary bone malignancy and typically arises from cartilage-producing cells. While surgery remains effective for localized disease, treatment options become extremely limited once tumors are unresectable or metastasize. Conventional chemotherapy and many targeted therapies have shown limited activity in this setting, leaving patients with poor outcomes and few therapeutic alternatives.
Ozekibart is a tetravalent death receptor 5 (DR5) agonist antibody that activates tumor cell death pathways through targeted DR5 signaling. The FDA previously granted Fast Track designation for metastatic or unresectable conventional chondrosarcoma in 2021, followed by orphan drug designation later that year.
ChonDRAgon Trial Demonstrated Significant PFS Benefit
The global ChonDRAgon study (NCT04950075) enrolled 206 patients across 67 sites and evaluated ozekibart against placebo in a randomized, blinded, placebo-controlled design. Eligible participants had grade 2 or grade 3 unresectable or metastatic conventional chondrosarcoma and were randomized in a 2:1 ratio to receive ozekibart or placebo every three weeks.
The study met its primary endpoint, demonstrating a statistically significant improvement in centrally reviewed progression-free survival. Ozekibart reduced the risk of disease progression or death by 52% versus placebo (HR 0.479; 95% CI, 0.33–0.68; P<0.0001). Median PFS more than doubled, reaching 5.52 months compared with 2.66 months in the placebo arm.
The treatment effect remained consistent across predefined patient subgroups, including both IDH-mutant and IDH-wild-type disease. Secondary endpoints also favored ozekibart, with disease control rates of 54% versus 27.5% for placebo and delayed deterioration in pain and physical function.
Manageable Safety Profile Supports Regulatory Review
Ozekibart was generally well tolerated. The most common treatment-related adverse events included fatigue, constipation, and nausea.
Investigators closely monitored hepatotoxicity, a recognized risk associated with DR5 agonism. One treatment-related fatal hepatic event occurred early in development before protocol modifications were introduced. Subsequent risk mitigation measures, including exclusion of patients with severe hepatic impairment and enhanced monitoring during early treatment cycles, substantially reduced the incidence of severe liver-related complications.
Treatment-related hepatic adverse events occurred in 11.8% of patients receiving ozekibart compared with 4.5% in the placebo arm, with most events classified as Grade 1 or Grade 2.
Regulatory Path Forward
FDA acceptance marks a pivotal regulatory milestone for Inhibrx, which has yet to commercialize a product. Beyond chondrosarcoma, the company continues to evaluate ozekibart in expansion cohorts studying irinotecan-based combination regimens in Ewing sarcoma and colorectal cancer.
The FDA’s decision, expected in April 2027, could establish ozekibart as the first approved systemic therapy for patients with unresectable or metastatic conventional chondrosarcoma and create a new treatment standard in a disease that has historically lacked effective drug options
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About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.