Ozekibart/FOLFIRI Yield Activity in Pretreated Advanced Colorectal Cancer

The combination of the investigational death receptor 5 (DR5) agonist antibody ozekibart (INBRX-109) and folinic acid, fluorouracil, and irinotecan (FOLFIRI) has demonstrated significant clinical activity in patients with heavily pretreated, locally advanced or metastatic colorectal cancer (CRC), according to a clinical update from the developer, Inhibrx Biosciences, Inc.¹

The combination therapy produced an objective response rate (ORR) that exceeded historical benchmarks for late-line treatments in this population. Ozekibart is a tetravalent single-domain antibody-based therapeutic candidate designed to induce tumor-selective programmed cell death by agonizing the DR5 receptor.

What efficacy and safety signals were observed with ozekibart plus FOLFIRI in late-line CRC?

As of the April 10, 2026, data cutoff date, the CRC cohort of the ongoing phase 1/2 trial (NCT03715933) demonstrated a confirmed ORR of 20% among 45 evaluable patients per RECIST v1.1. Durability was a key feature of the response data, as approximately half of the responding patients maintained their response for more than 6 months. The overall disease control rate (DCR) reached 87%, comprising patients who achieved either a partial response or stable disease. The median progression-free survival (PFS) for the evaluable population was 5.5 months, with 42% of patients remaining progression-free at the 6-month landmark. Clinical activity was observed regardless of the RAS or RAF mutation status of the tumors, suggesting that the pro-apoptotic mechanism of ozekibart may be effective across diverse molecular subtypes of colorectal adenocarcinoma.

The developer notes the ORR finding as notable when compared with historical response rates for the current late-line standards of care, which typically range from 1% to 6% per RECIST v1.1.

The safety profile of the ozekibart and FOLFIRI combination remained manageable and was largely characterized by adverse events typically associated with chemotherapy. The most frequently reported treatment-related adverse events were diarrhea, fatigue, and nausea, most of which were classified as grade 1 or 2 in severity. No significant liver toxicity was observed in this trial, and this lack of hepatic signal was notable given that 68% of the patients in the cohort presented with liver metastases at baseline.

Based on these results, the developer plans to discuss a registrational trial in the first line setting with the FDA in the second half of 2026, while also exploring potential accelerated approval pathways for ozekibart in the fourth-line setting of CRC.

“The meaningful response rate and PFS, together with a manageable safety profile in this heavily pre-treated 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 the press release.¹ “It also highlights the opportunity for broader expansion of ozekibart into other indications, which we continue to explore.”

How was the phase 1/2 trial of ozekibart in CRC structured?

The CRC cohort is part of an open-label, multicenter, first-in-human phase 1/2 study evaluating the safety and efficacy of ozekibart across multiple solid tumor types.² Eligible participants for the CRC arm had locally advanced or metastatic disease that had received at least 2 but no more than 3 prior lines of systemic therapy. Patients needed to be between 18 and 85 years of age, with measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, and an estimated life expectancy of at least 12 weeks.

Specifically, 70% of the cohort received the ozekibart combination as a fourth-line treatment, and 80% had previously experienced disease progression on an irinotecan-based regimen. The treatment regimen involved the administration of ozekibart in combination with a standard FOLFIRI backbone.

The primary end points of the trial were the frequency and severity of adverse events from ozekibart and tumor response for CRC and Ewing sarcoma.

This regulatory and clinical progress follows the April 2026 submission of a biologics license application (BLA) for ozekibart in conventional chondrosarcoma, an indication for which the agent previously received both fast track and orphan drug designations from the FDA.

References

1. Inhibrx provides clinical update on ozekibart (INBRX-109) in late line colorectal cancer. News release. Inhibrx Biosciences, Inc. April 21, 2026. Accessed April 22, 2026. https://tinyurl.com/4d72myer
2. 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 22, 2026. https://tinyurl.com/3rv7e795