The investigational death receptor 5 (DR5) agonist antibody ozekibart (INBRX-109) administered in combination with FOLFIRI (leucovorin calcium [folinic acid], fluorouracil, and irinotecan hydrochloride) produced durable responses and a manageable safety profile in patients with heavily pretreated, locally advanced or metastatic colorectal cancer (CRC), according to updated interim data from a phase 1/2 trial (NCT03715933).¹
At a data cutoff of April 10, 2026, evaluable patients in the CRC cohort (n = 45) achieved a confirmed overall response rate (ORR) of 20% per RECIST 1.1 criteria, with approximately half of patients maintaining their response for more than 6 months. The overall disease control rate was 87%. The median progression-free survival (PFS) was 5.5 months, with 42% of patients remaining progression-free at the 6-month landmark. Of note, clinical activity was observed regardless of RAS or RAF mutation status, suggesting that ozekibart’s pro-apoptotic mechanism may be effective across diverse CRC molecular subtypes.
According to the drug’s developer, Inhibrx Biosciences, Inc, ORRs seen with ozekibart exceed historical benchmarks for standard later-line regimens, which typically range from 1% to 6%.
Regarding safety, the regimen’s toxicity profile was largely characterized by chemotherapy-related adverse effects (AEs). The most frequently reported treatment-related AEs were diarrhea, fatigue, and nausea, the majority of which were grade 1/2 events. No significant liver toxicity was observed in this trial, despite 68% of patients in this cohort presenting with liver metastases at baseline.
“The meaningful response rate and PFS, together with a manageable safety profile in this heavily pretreated population, are highly encouraging and support our plans to advance into first line, where the potential for deeper and more durable responses may be even greater,” Mark Lappe, chief executive officer of Inhibrx Biosciences, stated in a news release. “It also highlights the opportunity for broader expansion of ozekibart into other indications, which we continue to explore.”1
What is the design of this phase 1/2 study?
This open-label, multicenter, first-in-human dose-escalation and multicohort expansion study is evaluating the safety and efficacy of ozekibart across solid tumors.2
All eligible patients must have measurable disease per RECIST 1.1 (or modified RECIST for mesothelioma) criteria; have adequate hematologic, coagulation, hepatic, and renal function; and have an ECOG performance status of 0 or 1, a Karnofsky Performance Status score of at least 60, or a Lansky Play-Performance Scale for Pediatric Functional Status score of at least 60 for patients younger than 16 years.
Additionally, in the CRC cohort, eligible patients must be between 18 and 85 years of age, have locally advanced or metastatic unresectable disease, and have been previously exposed to at least 2 but no more than 3 lines of systemic therapy.
Patients with Ewing sarcoma must be between 12 and 85 years of age; have histologically confirmed, locally advanced or metastatic, unresectable, relapsed or refractory Ewing sarcoma with a classical fusion; and must have received at least 1 but no more than 2 prior lines of systemic treatment with a preferred first-line chemotherapy regimen.
Ozekibart Gains Traction in CRC and Beyond
- Ozekibart plus FOLFIRI produced a confirmed ORR of 20%, a DCR of 87%, and a median PFS of 5.5 months in patients with heavily pretreated metastatic CRC in a phase 1/2 study.
- Clinical activity was observed irrespective of RAS or RAF mutation status, supporting a mutation-agnostic mechanism of action.
- Based on these data, the drug’s developer plans to discuss a registrational trial in the first-line setting with the FDA in the second half of 2026, as well as a pathway for accelerated approval in fourth-line CRC and Ewing sarcoma.
Upon enrollment, patients receive either single-agent ozekibart at either the maximum-tolerated dose or recommended phase 2 dose; or ozekibart in combination with chemotherapy.
The study’s primary end points are the frequency and severity of ozekibart-related AEs and tumor response for both CRC and Ewing sarcoma cohorts. Immunogenicity, pharmacokinetics, and PFS serve as key secondary end points.
What regulatory pathways and future development strategies are being pursued for ozekibart?
Based on the results from this phase 1/2 study, discussion of a registrational trial in the first-line setting with the FDA is planned for the second half of 2026.1 Inhibrx also plans to explore a potential pathway for accelerated approval of ozekibart in fourth-line CRC and Ewing sarcoma.
Of note, a biologics license application for ozekibart in conventional chondrosarcoma was also submitted to the FDA in April 2026 based on the agent’s demonstrated PFS benefit vs placebo in the phase 2/3 ChonDRAgon trial (NCT04950075). Ozekibart previously received fast track and orphan drug designations for the treatment of patients with metastatic or unresectable conventional chondrosarcoma and for chondrosarcoma, respectively, in 2021.
References
- Inhibrx provides clinical update on ozekibart (INBRX-109) in late line colorectal cancer. News release. Inhibrx Biosciences, Inc. April 21, 2026. Accessed April 29, 2026. https://inhibrxbiosciences.investorroom.com/2026-04-21-Inhibrx-Provides-Clinical-Update-on-Ozekibart-INBRX-109-in-Late-Line-Colorectal-Cancer
- Phase 1 study of INBRX-109 in subjects with locally advanced or metastatic solid tumors including sarcomas. ClinicalTrials.gov. Updated March 18, 2026. Accessed April 29, 2026. https://clinicaltrials.gov/study/NCT03715933
