FDA Accepts BLA for Ozekibart in Unresectable or Metastatic Chondrosarcoma

The FDA has accepted for filing a biologics license application (BLA) for ozekibart (INBRX-109) in patients with unresectable or metastatic conventional chondrosarcoma, with a Prescription Drug User Fee Act (PDUFA) goal date of April 14, 2027, Inhibrx Biosciences announced in a news release.¹ The FDA identified no filing review issues at this time.

If approved, ozekibart would become the first and only approved systemic therapy for patients with unresectable or metastatic conventional chondrosarcoma, a rare cancer arising in the cartilage cells of bones, most commonly affecting the pelvis, hip, and shoulder, for which no systemic treatment options currently exist.

“Chondrosarcoma is an aggressive and devastating bone cancer and there are currently no approved therapies for patients suffering from this disease," said Mark Lappe, chief executive officer of Inhibrx, in a news release. "We look forward to working closely with the FDA during this review process to potentially bring this first-in-class targeted therapy to patients as quickly as possible."

Supporting Trial Data

The BLA is supported by results from the ChonDRAgon study (NCT04950075), a randomized, blinded, placebo-controlled registrational trial of ozekibart in 206 patients with metastatic or unresectable conventional chondrosarcoma conducted across 67 sites worldwide. The trial enrolled patients with grade 2 or 3 disease and randomly assigned them 2:1 to ozekibart or placebo every 3 weeks, stratified by line of therapy, tumor grade, and IDH1/2 mutation status. Patients in the placebo arm were permitted to cross over to receive ozekibart upon confirmed progression by central independent radiology review.

The trial met its primary end point of a statistically significant and clinically meaningful improvement in median progression-free survival (PFS), assessed by central real-time independent radiology review per RECIST 1.1. Ozekibart achieved a 52% reduction in the risk of disease progression or death compared with placebo (stratified HR, 0.479; 95% CI, 0.33-0.68; P <.0001), more than doubling median PFS to 5.52 months vs 2.66 months for placebo.¹ Ozekibart is the first investigational therapy to demonstrate a significant PFS benefit in a blinded, randomized trial for chondrosarcoma.

PFS benefit was consistent across all prespecified subgroups, including patients with IDH–wild-type and IDH-mutant tumors. Key secondary end points further supported the primary result: disease control rate was 54% with ozekibart vs 27.5% with placebo, and ozekibart also demonstrated a statistically meaningful delay to deterioration in pain and physical function.² Additional secondary end points under evaluation include overall survival, objective response rate, and duration of response.

Drug Mechanism and Designations

Ozekibart is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to exploit tumor-biased cell death induced by DR5 activation. The FDA granted fast track designation to ozekibart for the treatment of patients with metastatic or unresectable conventional chondrosarcoma in January 2021 and orphan drug designation for chondrosarcoma in November 2021.

Safety

Ozekibart was generally well tolerated, with a manageable safety profile in the ChonDRAgon study.¹ The most common treatment-related adverse events were fatigue, constipation, and nausea. Hepatotoxicity, a known mechanism-related risk for DR5 agonists, was observed primarily during the first treatment cycle and in patients with underlying hepatic impairment.

One hepatotoxicity-related fatal adverse event occurred early in the study, prior to the implementation of mitigation measures. Risk was subsequently managed by excluding patients with severe liver impairment and implementing close monitoring during early treatment cycles. The overall incidence of treatment-related hepatic adverse events was 11.8% with ozekibart vs 4.5% with placebo, with the majority of events being grade 1 or 2.

Ongoing Development

Beyond chondrosarcoma, Inhibrx is evaluating ozekibart in expansion cohorts in combination with irinotecan-based regimens. In a cohort of 25 evaluable patients with refractory Ewing sarcoma receiving ozekibart plus irinotecan and temozolomide, the overall response rate (ORR) was 64% and the disease control rate was 92%, compared with a typical response rate of 15% to 30% with irinotecan and temozolomide alone. In 26 evaluable patients with heavily pretreated colorectal cancer receiving ozekibart plus folinic acid (Leucovorin), fluorouracil (5-FU), and irinotecan, the ORR was 23% and the disease control rate was 92%, compared with an estimated 5% to 6% with current standard of care in this setting. Inhibrx noted these results support further exploration in both tumor types.

REFERENCES

1. Inhibrx Announces U.S. FDA Acceptance of BLA for Ozekibart in Patients with Conventional Chondrosarcoma. News release. Inhibrx. June 15, 2026. Accessed June 15, 2026. https://tinyurl.com/5ftpzkpm

2. Gelderblom H, Wang V, Doherty M, et al. The tetravalent death receptor 5 (DR5) agonist ozekibart (INBRX-109) in conventional chondrosarcoma (CS): Secondary efficacy endpoints from the randomized, registrational, phase 2 ChonDRAgon study. J Clin Oncol. 2026;44(suppl 16):11504. doi:10.1200/JCO.2026.44.16_suppl.11504