INBRX-109 for Chondrosarcoma

(ChonDRAgon Trial)

No longer recruiting at 74 trial locations

Overseen By Study Director, -Inhibrx

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Inhibrx Biosciences, Inc

Must not be taking: DR5 agonists

Disqualifiers: Non-conventional chondrosarcoma, Chronic liver diseases, Multiple sclerosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called INBRX-109, an experimental drug, for individuals with chondrosarcoma that cannot be surgically removed or has metastasized. Researchers aim to determine if INBRX-109 can slow or halt cancer growth. Participants will receive either the experimental drug or a placebo (a substance with no active ingredient) every three weeks to compare outcomes. The trial seeks individuals with chondrosarcoma whose cancer has recently progressed and who have not previously received similar treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The protocol does not specify if you need to stop your current medications. Please consult with the trial coordinators for more details.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that INBRX-109 is likely to be safe for humans?

Previous studies have shown that INBRX-109 has a promising safety profile. Research indicates that patients with advanced chondrosarcoma, a type of bone cancer, tolerate it well. The trials focused mainly on safety, and the results were positive. Serious side effects occurred rarely, making it a potentially safe option for those considering participation in the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chondrosarcoma?

Unlike the standard treatments for chondrosarcoma, which primarily involve surgery and sometimes chemotherapy or radiation, INBRX-109 is unique because it harnesses a novel mechanism of action. INBRX-109 is a monoclonal antibody that targets and binds to the DR5 receptor on cancer cells, leading to their destruction. Researchers are excited about INBRX-109 because it offers a targeted approach, potentially increasing the effectiveness of treatment while minimizing damage to healthy cells. This could mean fewer side effects and better outcomes for patients with this challenging type of bone cancer.

What evidence suggests that INBRX-109 might be an effective treatment for chondrosarcoma?

Research has shown that INBRX-109, also known as ozekibart, may effectively treat chondrosarcoma, a type of bone cancer. In this trial, participants will receive either INBRX-109 or a placebo. One study found that patients taking ozekibart had a 52% lower chance of disease progression or death compared to those taking a placebo, which contains no active drug. This indicates that the drug helped slow the cancer's growth or spread. Earlier trials also found that INBRX-109 helped shrink or control tumor size. Overall, these findings suggest that INBRX-109 could be a promising treatment for patients with chondrosarcoma that cannot be surgically removed or has metastasized. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Lead

Principal Investigator

Inhibrx Biosciences, Inc

Are You a Good Fit for This Trial?

This trial is for people with a type of bone cancer called conventional chondrosarcoma that can't be removed by surgery or has spread. Participants must have shown disease progression recently, be in fairly good health (ECOG PS 0 or 1), and have a life expectancy of at least 12 weeks. They cannot join if they've had certain immune disorders like MS, allergies to the study drug or similar drugs made from Chinese hamster ovary cells, or previous treatment with DR5 agonists.

Inclusion Criteria

My cancer can be measured by scans and has grown since any local treatments like radiation.

Availability of archival tissue or fresh cancer biopsy are mandatory

I am fully active or can carry out light work.

Exclusion Criteria

I have a history of multiple sclerosis or similar conditions.

You are allergic to INBRX-109 or have known allergies to antibodies made from CHO cells.

I have been treated with DR5 agonists before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INBRX-109 or placebo intravenously every three weeks

3 years

Visits every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• INBRX-109

Trial Overview The study is testing INBRX-109 against a placebo in patients with advanced chondrosarcoma. It's a Phase 2 trial where participants are randomly assigned to receive either the real drug or a fake one without knowing which one they're getting. The goal is to see if INBRX-109 helps control the cancer better than no active treatment.

How Is the Trial Designed?

Group I: INBRX-109 Experimental Treatment 1 Intervention

IV every three weeks

Group II: Placebo Placebo Group 1 Intervention

IV every three weeks

INBRX-109 is already approved in United States for the following indications:

Approved in United States as INBRX-109 for:

• Chondrosarcoma (Orphan Drug Designation)

Who Is Running the Clinical Trial?

Inhibrx Biosciences, Inc

Lead Sponsor

Trials

9

Recruited

1,700+

Inhibrx, Inc.

Lead Sponsor

Trials

9

Recruited

1,700+

Published Research Related to This Trial

SF2523, a dual inhibitor of PI3K-Akt-mTOR and BRD4, effectively reduced survival, proliferation, and migration of chondrosarcoma cells while inducing apoptosis, showing promise as a therapeutic agent against this cancer.

In animal studies, SF2523 significantly inhibited tumor growth in mice without harming normal osteoblast cells, indicating its potential safety and efficacy in targeting chondrosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SF2523 inhibits human chondrosarcoma cell growth in vitro and in vivo. Zhu, JX., Xiao, JR.[2021]

The newly derived mesenchymal chondrosarcoma cell line MCS170 showed sensitivity to doxorubicin, with an IC50 of 0.09 μM, but was more resistant to cisplatin (IC50 of 4.5 μM) and had limited sensitivity to the BH3 mimetic ABT-737 (IC50 of 1.8 μM).

Combining ABT-737 with conventional chemotherapy (doxorubicin or cisplatin) resulted in a synergistic effect, enhancing apoptosis and reducing cell proliferation, suggesting that targeting Bcl-2 family members could improve treatment outcomes for mesenchymal chondrosarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Bcl-2 family members sensitizes mesenchymal chondrosarcoma to conventional chemotherapy: report on a novel mesenchymal chondrosarcoma cell line. de Jong, Y., van Maldegem, AM., Marino-Enriquez, A., et al.[2023]

The novel compound ACDB effectively induces apoptosis in human chondrosarcoma cells while sparing normal chondrocytes, suggesting a targeted therapeutic approach with potentially fewer side effects.

ACDB triggers endoplasmic reticulum (ER) stress and mitochondrial dysfunction, leading to the activation of apoptotic pathways, and has been shown to reduce tumor volume in animal models, indicating its potential as a new treatment for chondrosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel benzofuran derivative, ACDB, induces apoptosis of human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress. Su, CM., Chen, CY., Lu, T., et al.[2018]

The analysis of the FDA's Adverse Event Reporting System revealed significantly elevated risks of pulmonary thrombosis with tofacitinib and pulmonary embolism with baricitinib, indicating potential safety concerns for these JAK inhibitors.

Ruxolitinib was associated with increased rates of portal vein thrombosis, and both baricitinib and ruxolitinib showed heightened reports of deep vein thrombosis, suggesting that JAKinibs may not be safe for patients with a history of thromboembolic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of Thromboembolic Events with JAK Inhibitors: Analysis of the FAERS Database 2010-2019. Setyawan, J., Azimi, N., Strand, V., et al.[2022]

Tofacitinib, an oral Janus kinase inhibitor, significantly improved symptoms in Chinese patients with active psoriatic arthritis compared to placebo, achieving a 38.2% ACR50 response at 3 months versus 5.9% for placebo (p<0.0001).

The safety profile of tofacitinib was consistent with previous studies, showing a lower incidence of serious adverse events compared to placebo, with no major cardiovascular events or non-melanoma skin cancers reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis: a phase 3, randomised, double-blind, placebo-controlled study. Leng, X., Lin, W., Liu, S., et al.[2023]

Janus kinase inhibitors, including new compounds like filgotinib and upadacitinib, show promising fast and dose-dependent clinical improvements in treating rheumatoid arthritis, comparable to existing treatments like tofacitinib and baricitinib.

While these new drugs have similar adverse events, some side effects are specific to individual drugs, highlighting the need for thorough phase III trials and safety evaluations to optimize their use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of new JAK inhibitors under development. Just more of the same? Westhovens, R.[2023]

The new benzimidazole derivative, BPB, effectively induces apoptosis in human chondrosarcoma cells while sparing normal chondrocytes, suggesting a targeted anticancer mechanism.

In animal studies, BPB treatment resulted in a significant 40% reduction in tumor volume over 21 days, indicating its potential as a novel therapeutic agent for chondrosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1-benzyl-2-phenylbenzimidazole (BPB), a benzimidazole derivative, induces cell apoptosis in human chondrosarcoma through intrinsic and extrinsic pathways. Liu, JF., Huang, YL., Yang, WH., et al.[2021]

Chondrosarcoma, particularly in its metastatic or unresectable forms, is challenging to treat due to resistance to standard anticancer therapies, highlighting the need for novel treatments.

Recent research has identified promising biomarkers like IDH1/2 and COL2A1, and several targeted therapies and immunotherapies have shown encouraging antitumor activity in clinical studies for advanced chondrosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Targets and Emerging Treatments in Advanced Chondrosarcoma. Miwa, S., Yamamoto, N., Hayashi, K., et al.[2022]

BH3 mimetics ABT-737 and ABT-263 effectively inhibit the growth of chondrosarcoma cells in vitro and induce apoptosis, suggesting a potential new treatment approach for this chemotherapy-resistant cancer.

In vivo studies using a mouse model demonstrated that ABT-263 not only inhibited chondrosarcoma growth but also improved survival, highlighting its efficacy as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BH3 mimetics inhibit growth of chondrosarcoma--a novel targeted-therapy for candidate models. Morii, T., Ohtsuka, K., Ohnishi, H., et al.[2014]

A second case of a chondrogenic tumor was identified in a 41-year-old woman, diagnosed as chondromyxoid fibroma, which also carried the IRF2BP2::CDX1 fusion gene, suggesting a potential link between this genetic alteration and chondrogenic tumors.

The presence of the IRF2BP2::CDX1 chimera in these tumors indicates a possible recurrent genetic feature, although more data is needed to determine if it is associated with benign or malignant tumor behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fusion of the Genes for Interferon Regulatory Factor 2 Binding Protein 2 (IRF2BP2) and Caudal Type Homeobox 1 (CDX1) in a Chondrogenic Tumor. Panagopoulos, I., Gorunova, L., Lobmaier, I., et al.[2023]

In a phase 2 study involving 47 patients with unresectable or metastatic conventional chondrosarcoma, pazopanib demonstrated a disease control rate of 43% at 16 weeks, indicating its potential effectiveness in managing this type of cancer.

The median overall survival for patients was 17.6 months, with manageable side effects, primarily hypertension (26%) and elevated liver enzymes (9%), suggesting that pazopanib is a relatively safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a prospective phase 2 study of pazopanib in patients with surgically unresectable or metastatic chondrosarcoma. Chow, W., Frankel, P., Ruel, C., et al.[2021]

Janus kinase inhibitors (JAKi) are commonly used for treating immune-mediated inflammatory diseases like psoriatic arthritis, but recent studies have raised safety concerns, particularly in patients over 50 with cardiac risk factors.

This review summarizes the latest safety data for various JAKi, including tofacitinib and upadacitinib, and discusses findings from an oral surveillance study to provide context for these safety issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus Kinase Inhibitors: Safety in Patients With Psoriatic Arthritis. Nash, P.[2022]

CP-690,550 is an effective oral JAK inhibitor that showed significant improvement in rheumatoid arthritis symptoms in Phase II trials, with robust ACR20 responses at mid to high doses.

While CP-690,550 demonstrated efficacy, it was associated with side effects such as headaches, nausea, and an increased risk of infections, along with changes in blood parameters like elevated cholesterol and decreased hemoglobin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes. Riese, RJ., Krishnaswami, S., Kremer, J.[2016]

Citations

1. inhibrx.investorroom.com inhibrx.investorroom.com/2025-10-23-Inhibrx-Biosciences-Reports-Positive-Topline-Results-from-its-Registrational-Trial-of-Ozekibart-INBRX-109-in-Chondrosarcoma-and-Provides-Updates-on-Colorectal-Cancer-and-Ewing-Sarcoma-Expansion-Cohorts

Inhibrx Biosciences Reports Positive Topline Results from its ... ... chondrosarcoma treated with ozekibart compared to placebo. Ozekibart achieved a 52% reduction in the risk of disease progression or death ...

2. clinicaltrialsarena.com clinicaltrialsarena.com/news/inhibrx-biosciences-ozekibart-chondrosarcoma-phase-ii/

Inhibrx Biosciences' stock soars on chondrosarcoma ... Meanwhile, the drug also showed promise in relapsed/refractory Ewing sarcoma, demonstrating an ORR of 64% and a DCR of 92%. In a 24 October ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04950075

Study of INBRX-109 in Conventional Chondrosarcoma This is a randomized, blinded, placebo-controlled, Phase 2 study of INBRX-109 in unresectable or metastatic conventional chondrosarcoma patients.

4. finance.yahoo.com finance.yahoo.com/news/inhibrx-biosciences-reports-positive-topline-200500734.html

Inhibrx Biosciences Reports Positive Topline Results from ... ... chondrosarcoma treated with ozekibart compared to placebo. Ozekibart achieved a 52% reduction in the risk of disease progression or death ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10425732/

Preclinical Characterization and Phase I Trial Results of ... INBRX-109 demonstrated encouraging antitumor activity with a favorable safety profile in patients with unresectable/metastatic chondrosarcoma.

6. inhibrx.com inhibrx.com/ozekibart-inbrx-109/

ozekibart (INBRX-109) Sarcoma Trials for 2025 The registration-enabling phase 2 trial for ozekibart (INBRX-109) (NCT04950075) is in patients with unresectable or metastatic conventional chondrosarcoma.

7. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO.2025.43.4_suppl.129

Tetravalent death receptor 5 (DR5) agonist ozekibart ( ... The primary endpoint is safety; clinical response is an exploratory endpoint. Results: In total, 13 pts with CRC (male, 62%) received ozekibart + FOLFIRI.