Inhibrx Biosciences Highlights 20% ORR for Ozekibart Combo in Late-Line Colorectal Cancer

Key Points

• Inhibrx reported that ozekibart plus FOLFIRI produced a 20% ORR and a median PFS of 5.5 months in 45 heavily pretreated advanced colorectal cancer patients, with nearly half of responses lasting >6 months and >41% progression-free at six months.
• The combination had a manageable safety profile—mostly low-grade diarrhea, fatigue and nausea—and the company observed no significant liver toxicity despite 68% of patients having liver metastases.
• Inhibrx plans to move ozekibart into earlier lines, including an FDA meeting in H2 to discuss a ~500‑patient first-line registrational study targeting a PFS improvement from 11 to 16 months, alongside second- and third-line cohorts and potential accelerated pathways.

Inhibrx Biosciences NASDAQ: INBX shared a clinical update on ozekibart in advanced colorectal cancer, highlighting Phase I/II data evaluating ozekibart in combination with FOLFIRI in a heavily pretreated population that company executives said has historically seen minimal benefit from standard options.

Late-line colorectal cancer data and patient population

Founder and CEO Mark Lappe said the company’s newly released results involved 45 evaluable patients with advanced or metastatic unresectable colorectal cancer (CRC). According to Lappe, 70% of patients received ozekibart plus FOLFIRI as fourth-line therapy and 30% received it as third-line therapy. He added that 80% of patients were already refractory to irinotecan.

Lappe contrasted the study outcomes with historical expectations in this setting, describing the standard of care as having an objective response rate (ORR) of “almost zero” and a median progression-free survival (PFS) of “only two to three months.”

In the ozekibart combination cohort, Lappe reported an ORR of 20% and said “nearly half of those responses were durable for over six months.” Median PFS was 5.5 months, and he said that at the six-month mark, “over 41% of these patients remain progression-free.” Lappe also noted that nine patients were still on treatment as of the data cutoff date, arguing this suggests durable benefit among patients who achieve disease control.

Safety observations

On tolerability, Lappe said the most common treatment-emergent adverse events included diarrhea, fatigue, and nausea, with most events described as low-grade and consistent with known side effects of FOLFIRI. He also emphasized liver safety in a cohort where 68% of patients entered the study with liver metastases, stating the company observed “no significant liver toxicity” in these patients.

Lappe said the combination’s manageable safety profile, alongside the efficacy signal, supports the company’s intention to move ozekibart into earlier lines of CRC treatment.

Mechanism and rationale for activity

In a Q&A session, Lappe discussed Inhibrx’s approach to targeting DR5, saying ozekibart’s format—“four binding domains”—was designed to achieve agonism while avoiding unwanted effects. He said the company’s view is that “it needs to be a tetramer” to act as an agonist, while going beyond that could increase engagement with “healthy hepatocyte” populations.

Lappe also pointed to preclinical and clinical observations suggesting synergy with irinotecan. He said irinotecan can stress tumor cells and make them “much more susceptible” to DR5 agonism, adding that this was seen previously in Ewing sarcoma data and is now “becoming apparent in the colorectal data as well.”

He further referenced single-agent activity observed in a registrational study in chondrosarcoma as supporting confidence in the mechanism, and noted potential future interest in combinations involving “topoisomerase-based class of ADCs” because they are “essentially irinotecan based.”

Regulatory discussions and development plans

Lappe said Inhibrx plans to meet with the FDA in the second half of the year to discuss a registrational trial in first-line CRC. He also said the company intends to discuss potential accelerated regulatory pathways for unresectable refractory Ewing sarcoma and unresectable metastatic CRC in the fourth-line setting, while cautioning that timing and outcomes cannot be predicted.

He expressed optimism about an accelerated approval pathway in Ewing sarcoma, citing what he described as a superior response rate and disease control rate in a high unmet-need indication that is “predominantly a pediatric indication.” For fourth-line CRC, Lappe said an accelerated path “might be a bigger ask” given the number of available treatments, but he argued existing therapies show limited efficacy in late-line CRC and said the company believes the data are strong enough to pursue discussions.

Trial design details: first-, second-, and third-line CRC

Lappe provided additional specifics on the company’s planned CRC development strategy. He said Inhibrx is aiming for a first-line registrational study that it would plan to initiate around the end of the year or early next year. The proposed design would evaluate ozekibart plus either FOLFIRI and bevacizumab or FOLFOXIRI and bevacizumab, versus control regimens of either FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab.

He said PFS would be the primary endpoint and described the trial as “approximately about a 500-patient study,” targeting a PFS improvement of about five months (from 11 to 16 months), corresponding to a hazard ratio less than 0.68. Lappe described an estimated two-year enrollment period and about a one-year follow-up for PFS, with a readout timeframe “sometime in 2030.” He said the study would be conducted in an “all-comers” population, with the expectation that ozekibart could work irrespective of mutation status.

Beyond first line, Lappe said Inhibrx is starting a second-line Phase I/II single-arm cohort of ozekibart plus FOLFIRI and bevacizumab in about 30 to 40 patients, primarily to generate safety data for the triplet combination. He also said the company is initiating a third-line study of ozekibart plus Lonsurf and bevacizumab, citing preclinical synergy and the practical challenge of using FOLFIRI again for patients who already received it in second line.

When asked about readiness to begin a frontline study and possible gating factors, Lappe said the company does not see barriers such as manufacturing constraints. He said Inhibrx expects to have “a large amount of drug supply” that will be commercially ready, and described plans to generate second-line safety data with bevacizumab alongside preparation for the registrational program.

In closing remarks, Lappe said the CRC results support ozekibart as “not only a sarcoma drug” but one with broader potential across solid tumors, which he said could expand commercial opportunities and provide additional options for patients.

About Inhibrx Biosciences NASDAQ: INBX

Inhibrx, Inc, headquartered in La Jolla, California, is a clinical-stage biotechnology company focused on the discovery and development of next-generation protein therapeutics. The company's proprietary protein engineering platform enables the design and production of multispecific and multivalent biologics with tailored binding characteristics and favorable pharmacokinetic properties. By leveraging high-throughput screening and structure-based design, Inhibrx aims to create molecules that address challenging targets in oncology, regenerative medicine and other areas of unmet medical need.

The company's lead candidate, INBRX-109, is a tetravalent agonist of the receptor tyrosine kinase ROR2 designed to stimulate tissue repair and regeneration.

This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to contact@marketbeat.com.