Inhibrx seeks first systemic therapy approval in chondrosarcoma with ozekibart filing

San Diego-based Inhibrx Biosciences, Inc. (Nasdaq: INBX) announced that the US FDA has accepted a Biologics License Application (BLA) for ozekibart (INBRX-109), a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody, filed for the treatment of patients with unresectable or metastatic conventional chondrosarcoma. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of April 14, 2027. If approved, ozekibart would be the first systemic therapy approved for this indication and Inhibrx’s first commercial product.

The BLA was submitted in April 2026 and carries Fast Track designation, granted in January 2021, along with orphan drug designation awarded in November 2021 for chondrosarcoma.

The filing is supported by the ChonDRAgon study, a randomized, blinded, placebo-controlled registrational trial enrolling 206 patients with grade 2 or 3 unresectable or metastatic conventional chondrosarcoma across 67 sites. Topline results reported in October 2025 demonstrated that ozekibart met its primary endpoint, more than doubling median progression-free survival (PFS) to 5.52 months versus 2.66 months for placebo (stratified hazard ratio 0.479; 95% CI: 0.33, 0.68; p<0.0001), representing a 52% reduction in the risk of disease progression or death. The benefit was consistent across IDH-wild-type and IDH-mutant subgroups. Key secondary endpoints also supported the primary finding: disease control rate was 54% with ozekibart versus 27.5% with placebo, and treatment demonstrated delay in deterioration of pain and physical function. The most common treatment-related adverse events were fatigue, constipation, and nausea. Hepatotoxicity, a mechanism-related risk, occurred predominantly in patients with underlying hepatic impairment during the first treatment cycle; following protocol amendments excluding patients with severe liver impairment and implementing close monitoring, the overall incidence of treatment-related hepatic adverse events was 11.8% in the ozekibart arm versus 4.5% in the placebo arm, with the majority Grade 1 or 2.

Ozekibart functions by activating DR5 to induce tumor-biased apoptosis. The tetravalent format is central to its design: DR5 agonism requires receptor clustering to trigger apoptotic signaling, and the multivalent architecture is intended to drive this clustering more potently than conventional bivalent antibodies while exploiting the preferential DR5 expression on malignant cells.

Conventional chondrosarcoma, the second most common primary bone malignancy, is largely unresponsive to chemotherapy and radiotherapy, leaving surgical resection as the only established treatment for localized disease. No systemic therapy has previously been approved for the unresectable or metastatic setting.

The investigational pipeline is narrow. France-based Servier’s ivosidenib (Tibsovo), an IDH1 inhibitor already approved in acute myeloid leukemia and cholangiocarcinoma, is being evaluated in the Phase III CHONQUER trial (NCT06127407) in IDH1-mutant conventional chondrosarcoma, with primary completion anticipated in February 2028. Eli Lilly’s LY3410738, an IDH1/2 inhibitor, is also in clinical evaluation for this indication. Critically, both ivosidenib and LY3410738 are restricted to IDH-mutant tumors, which represent approximately 50%-70% of cases. Ozekibart, by contrast, demonstrated consistent benefit regardless of IDH mutation status, positioning it as a potentially broader-use agent in this setting. Updated interim data from an expansion cohort in late-line colorectal cancer, reported in April 2026, showed a 20% objective response rate and 87% disease control rate in 45 evaluable heavily pretreated patients as of the April 10, 2026 cutoff, supporting Inhibrx’s plans to explore ozekibart across additional solid tumor indications including Ewing sarcoma.

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