INBRX-109 for Chondrosarcoma
(ChonDRAgon Trial)
Recruiting in Palo Alto (17 mi)
+72 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Inhibrx Biosciences, Inc
Prior Safety Data
Approved in 1 Jurisdiction
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.
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.
12345What 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.
678910Eligibility 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.
+5 more
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.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: INBRX-109Experimental Treatment1 Intervention
IV every three weeks
Group II: PlaceboPlacebo Group1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PennsylvaniaPhiladelphia, PA
University of WashingtonSeattle, WA
University of Oklahoma - Stephenson Cancer CenterOklahoma City, OK
Precision NextGen Oncology & Research CenterBeverly Hills, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Inhibrx Biosciences, IncLead Sponsor
Inhibrx, Inc.Lead Sponsor
References
Therapeutic Targets and Emerging Treatments in Advanced Chondrosarcoma. [2022]Due to resistance to standard anticancer agents, it is difficult to control the disease progression in patients with metastatic or unresectable chondrosarcoma. Novel therapeutic approaches, such as molecule-targeting drugs and immunotherapy, are required to improve clinical outcomes in patients with advanced chondrosarcoma. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including IDH1/2 and COL2A1. Several molecule-targeting agents and immunotherapies have shown favorable antitumor activity in clinical studies in patients with advanced chondrosarcomas. This review summarizes recent basic studies on biomarkers and molecular targets and recent clinical studies on the treatment of chondrosarcomas.
1-benzyl-2-phenylbenzimidazole (BPB), a benzimidazole derivative, induces cell apoptosis in human chondrosarcoma through intrinsic and extrinsic pathways. [2021]In this study, we investigated the anticancer effects of a new benzimidazole derivative, 1-benzyl-2-phenyl -benzimidazole (BPB), in human chondrosarcoma cells. BPB-mediated apoptosis was assessed by the MTT assay and flow cytometry analysis. The in vivo efficacy was examined in a JJ012 xenograft model. Here we found that BPB induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353) but not in primary chondrocytes. BPB induced upregulation of Bax, Bad and Bak, downregulation of Bcl-2, Bid and Bcl-XL and dysfunction of mitochondria in chondrosarcoma. In addition, BPB also promoted cytosolic releases AIF and Endo G. Furthermore, it triggered extrinsic death receptor-dependent pathway, which was characterized by activating Fas, FADD and caspase-8. Most importantly, animal studies revealed a dramatic 40% reduction in tumor volume after 21 days of treatment. Thus, BPB may be a novel anticancer agent for the treatment of chondrosarcoma.
Results of a prospective phase 2 study of pazopanib in patients with surgically unresectable or metastatic chondrosarcoma. [2021]This single-arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable or metastatic conventional chondrosarcoma.
A novel benzofuran derivative, ACDB, induces apoptosis of human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress. [2018]Chondrosarcoma is one of the bone tumor with high mortality in respond to poor radiation and chemotherapy treatment. Here, we analyze the antitumor activity of a novel benzofuran derivative, 2-amino-3-(2-chlorophenyl)-6-(4-dimethylaminophenyl)benzofuran-4-yl acetate (ACDB), in human chondrosarcoma cells. ACDB increased the cell apoptosis of human chondrosarcomas without harm in chondrocytes. ACDB also enhanced endoplasmic reticulum (ER) stress, which was characterized by varieties in the cytosolic calcium levels and induced the expression of glucose-regulated protein (GRP) and calpain. Furthermore, the ACDB-induced chondrosarcoma apoptosis was associated with the upregulation of the B cell lymphoma-2 (Bcl-2) family members including pro- and anti-apoptotic proteins, downregulation of dysfunctional mitochondria that released cytochrome C, and subsequent activation of caspases-3. In addition, the ACDB-mediated cellular apoptosis was suppressed by transfecting cells with glucose-regulated protein (GRP) and calpain siRNA or treating cells with ER stress chelators and caspase inhibitors. Interestingly, animal experiments illustrated a reduction in the tumor volume following ACDB treatment. Together, these results suggest that ACDB may be a novel tumor suppressor of chondrosarcoma, and this study demonstrates that the novel antitumor agent, ACDB, induced apoptosis by mitochondrial dysfunction and ER stress in human chondrosarcoma cells in vitro and in vivo.
BH3 mimetics inhibit growth of chondrosarcoma--a novel targeted-therapy for candidate models. [2014]Chondrosarcoma is refractory to conventional chemotherapy. BH-3 mimetics ABT-737 and ABT-263 are synthetic small-molecule inhibitors of anti-apoptotic proteins B-cell lymphoma-2 (Bcl2) and Bcl-xL, which play a critical role in survival of chondrosarcoma cells.
Reporting of Thromboembolic Events with JAK Inhibitors: Analysis of the FAERS Database 2010-2019. [2022]A potentially elevated risk for pulmonary thrombosis with Janus kinase inhibitors (JAKinibs) was identified, as well as an increased risk for portal vein thrombosis, in ruxolitinib patients. Consequently, the objective of this investigation was to repeat a comprehensive analysis of the US FDA's Adverse Event Reporting System (FAERS) database to assess postmarketing reporting rates of thromboembolic events (TEs) in patients treated with JAKinibs.
Janus Kinase Inhibitors: Safety in Patients With Psoriatic Arthritis. [2022]Janus kinase inhibitors (JAKi; or Jakinibs) have become widely prescribed around the world for a variety of immune-mediated inflammatory diseases, including psoriatic arthritis. A previous noninferiority surveillance study of patients aged > 50 years with rheumatoid arthritis and ≥ 1 additional cardiac risk factor raised a number of safety concerns. This review focuses on available safety data from peer-reviewed publications, as well as the most recent presentations from major conferences highlighting JAKi-associated adverse effects. The safety data for several types of JAKi are reviewed. The latest available safety data for tofacitinib, upadacitinib, filgotinib, deucravacitinib, and brepocitinib is presented. In addition, the findings from the oral surveillance study will be discussed to put safety concerns into context.
Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis: a phase 3, randomised, double-blind, placebo-controlled study. [2023]Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug.
Clinical efficacy of new JAK inhibitors under development. Just more of the same? [2023]Janus kinase inhibition is promising in the treatment of RA, with already two oral drugs marketed. New compounds are under investigation that are more selective for Janus kinase 1 or Janus kinase 3. Phase II results for filgotinib, upadacitinib, peficitinib and decernotinib are reviewed showing almost consistently a fast dose-dependent clinical improvement similar to already approved drugs tofacitinib and baricitinib. I will reflect on the most frequently reported dose-dependent adverse events and laboratory changes. Some are similar for all drugs of this class, some are more specific for a certain drug, but all may influence future treatment effectiveness in daily practice. This implies the need for a critical evaluation of phase III trials, and eventually trials specifically powered for conclusions on the safety profile and registries once these drugs become marketed. These innovative drugs also need head-to-head trials versus biologics or in-class as well as specific strategy studies to determine their optimal future use.
Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes. [2016]CP-690,550 is an orally active and selective inhibitor of the janus kinase (JAK) molecules. The molecular pathways through which the JAK moieties function are described along with the clinical mechanisms associated with their inhibition. Animal models of JAK inhibition are reviewed as a background for the possible inhibition of JAK in humans. The pharmacokinetics of CP-690,550 in humans is described, and the Phase IIA and IIB trials are reviewed in some detail. These trials were dose-ranging and showed a general dose response with relatively robust American College of Rheumatology 20 (ACR20) responses. A proof-of-concept 6-week trial in which CP-690,550 was given as monotherapy was associated with highly efficacious responses at the mid and higher twice-daily dose ranges employed. A subsequent 24 week dose-ranging trial in which CP-690,550 was administered in combination with methotrexate showed ACR20 responses, which were also statistically significant versus placebo interventions. CP-690,550 treatment was associated with side effects, which included headache and nausea. Infections were more common versus placebo as were elevations in transaminase enzymes when administered in combination with methotrexate, and increases in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. Decreases in haemoglobin and white blood cell (WBC) counts were also observed along with small increases in serum creatinine. Occasional significant decreases of haemoglobin (>2 g dl(-1)) were observed, although decreases of WBC to less than 1000 per mm(3) were not seen. Plans for long-term follow-up of the described trials are described along with the features of five presently ongoing Phase III trials of the CP-690,550 janus kinase (JAK) inhibitor. Future directions include completion and publication of these trials along with study of JAK inhibition for other indications.
Fusion of the Genes for Interferon Regulatory Factor 2 Binding Protein 2 (IRF2BP2) and Caudal Type Homeobox 1 (CDX1) in a Chondrogenic Tumor. [2023]Chondrogenic tumors are benign, intermediate or malignant neoplasms showing cartilaginous differentiation. In 2012, we reported a mesenchymal chondrosarcoma carrying a t(1;5)(q42;q32) leading to an IRF2BP2::CDX1 fusion gene. Here, we report a second chondrogenic tumor carrying an IRF2BP2::CDX1 chimera.
SF2523 inhibits human chondrosarcoma cell growth in vitro and in vivo. [2021]Developing novel therapeutic agents against chondrosarcoma is important. SF2523 is a PI3K-Akt-mTOR and bromodomain-containing protein 4 (BRD4) dual inhibitor. Its activity in human chondrosarcoma cells is tested. Our results show that SF2523 potently inhibited survival, proliferation and migration, and induced apoptosis activation in SW1353 cells and primary human chondrosarcoma cells. The dual inhibitor was yet non-cytotoxic to the primary human osteoblasts and OB-6 osteoblastic cells. SF2523 blocked Akt-mTOR activation and downregulated BRD4-regulated genes (Bcl-2 and c-Myc) in chondrosarcoma cells. It was more efficient in killing chondrosarcoma cells than other established PI3K-Akt-mTOR and BRD4 inhibitors, including JQ1, perifosine and OSI-027. In vivo, intraperitoneal injection of SF2523 (30 mg/kg) potently inhibited subcutaneous SW1353 xenograft tumor growth in severe combined immunodeficient mice. Akt-mTOR inhibition as well as Bcl-2 and c-Myc downregulation were detected in SF2523-treated SW1353 tumor tissues. In conclusion, targeting PI3K-Akt-mTOR and BRD4 by SF2523 potently inhibited chondrosarcoma cell growth in vitro and in vivo.
Inhibition of Bcl-2 family members sensitizes mesenchymal chondrosarcoma to conventional chemotherapy: report on a novel mesenchymal chondrosarcoma cell line. [2023]Mesenchymal chondrosarcomas are rare and highly aggressive sarcomas occurring in bone and soft tissue, with poor overall survival. Bcl-2 expression was previously shown to be upregulated in mesenchymal chondrosarcomas. We here report on a newly derived mesenchymal chondrosarcoma cell line, MCS170, in which we investigated treatment with the BH3 mimetic ABT-737 alone or in combination with conventional chemotherapy as a possible new therapeutic strategy. The presence of the characteristic HEY1-NCOA2 fusion was confirmed in the MCS170 cell line using FISH, RT-PCR, and sequencing. The MCS170 cell line was treated with ABT-737 alone or in combination with doxorubicin or cisplatin. Cell viability and proliferation was determined using WST-1 viability assays and the xCELLigence system. Expression of Bcl-2 family members was studied using immunohistochemistry. Apoptosis was determined using the caspase-glo 3/7 assay and western blot for PARP cleavage. The MCS170 cell line was sensitive to doxorubicin treatment with an IC50 of 0.09 μM after 72 h, but more resistant to cisplatin treatment with an IC50 of 4.5 μM after 72 h. Cells showed little sensitivity toward ABT-737 with an IC50 of 1.8 μM after 72 h. Combination treatments demonstrated ABT-737 synergism with cisplatin as well as doxorubicin as shown by induction of apoptosis and reduction in cell proliferation. Restoration of the apoptotic machinery by inhibition of Bcl-2 family members sensitizes MCS170 mesenchymal chondrosarcoma cells to conventional chemotherapy. This indicates that combining the inhibition of Bcl-2 family members with conventional chemotherapy can be a possible therapeutic strategy for patients with mesenchymal chondrosarcoma.