INBRX-109 for Chondrosarcoma

(ChonDRAgon Trial)

Recruiting at 72 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

201 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests INBRX-109, a specially designed protein, in patients with a hard-to-treat type of bone cancer. The treatment helps the immune system target and kill cancer cells by attaching to a specific marker on these cells.

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.

What data supports the idea that INBRX-109 for Chondrosarcoma is an effective treatment?

The available research does not provide specific data on the effectiveness of INBRX-109 for Chondrosarcoma. However, it mentions other treatments like BPB and ACDB, which have shown promising results in reducing tumor size in chondrosarcoma. For example, BPB led to a 40% reduction in tumor volume in animal studies. These findings suggest that there are emerging treatments for chondrosarcoma, but specific data on INBRX-109 is not available in the provided information. ^{1 2 3 4 5}

What safety data is available for INBRX-109 (also known as JCT-205 or Ozekibart) in treating Chondrosarcoma?

The provided research does not contain any safety data for INBRX-109, JCT-205, or Ozekibart. The studies focus on Janus kinase inhibitors (JAKinibs) and their safety profiles, which are unrelated to INBRX-109 or its other names. ^{6 7 8 9 10}

Is the drug INBRX-109 a promising treatment for chondrosarcoma?

The information provided does not mention INBRX-109, so we cannot determine if it is a promising treatment for chondrosarcoma based on the given research articles. ^{2 3 11 12 13}

Research Team

Clinical Lead

Principal Investigator

Inhibrx Biosciences, Inc

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Targets and Emerging Treatments in Advanced Chondrosarcoma. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

1-benzyl-2-phenylbenzimidazole (BPB), a benzimidazole derivative, induces cell apoptosis in human chondrosarcoma through intrinsic and extrinsic pathways. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Results of a prospective phase 2 study of pazopanib in patients with surgically unresectable or metastatic chondrosarcoma. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

A novel benzofuran derivative, ACDB, induces apoptosis of human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress. [2018]

5. Greece pubmed.ncbi.nlm.nih.gov

BH3 mimetics inhibit growth of chondrosarcoma--a novel targeted-therapy for candidate models. [2014]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Reporting of Thromboembolic Events with JAK Inhibitors: Analysis of the FAERS Database 2010-2019. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

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

8. England 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes. [2016]

11. Greece 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. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

SF2523 inhibits human chondrosarcoma cell growth in vitro and in vivo. [2021]

13. United States 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. [2023]