A Randomized, Blinded, Placebo-controlled, Phase 2 Study of INBRX-109 in Unresectable or Metastatic Conventional Chondrosarcoma

Phase 2

Recruiting

Conditions: Conventional chondrosarcomas
malignant bone tumor
10005959

Registration Number: NL-OMON54090

Lead Sponsor: Inhibrx, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 18

Inclusion Criteria

To be eligible for study entry patients must satisfy all of the following
criteria:
1. Males or females aged >= 18 to <= 85 years.
Note: Potential inclusion of patients who are chronologically older than 85
years, but with Eastern Cooperative Group Performance Status (ECOG PS) 0 and a
younger biologic age per comprehensive geriatric assessment, must be based on
discussion with the Medical Monitor or Study Director.
2. Conventional (or primary) chondrosarcoma (Note: must be confirmed by local
institutional or reference pathology review, but this confirmation is not
required for enrollment)
• Metastatic or unresectable (i.e., not amenable to tumor resection with
curative intent),
• The availability of archival tissue or a fresh cancer biopsy is mandatory for
enrollment.
- Note: A confirmation of IDH mutational status (per Clinical Laboratory
Improvement Amendments [CLIA]-certified assay or equivalent) is required for
stratification prior to randomization, any status is allowed, i.e. IDH1, IDH2
or wildtype.
• Any number of prior lines of systemic therapy are allowed.
- Note: Since there are no FDA/EMA approved systemic therapies for this
population, patients with unresectable and/or metastatic disease who have not
received prior systemic therapy may be eligible, provided that they have
exhausted all clinically relevant (localized and/or palliative) treatment
options as per investigator*s preference as per local practice guidelines.
• Furthermore, patients with oligometastatic disease (low disease burden,
resectable) must have exhausted all clinically relevant options including
palliative radiation, surgery or chemotherapy with non-curative intent.
3. Measurable disease by RECISTv1.1.
• Note: Tumor lesions that are located in a previously irradiated (or other
locally treated) area will be considered measurable, provided there has been
clear imaging-based progression of the lesions since the time of radiation.
4. Evidence of confirmed radiographic disease progression per RECISTv1.1
criteria within 6 months prior to the start of the study treatment
• Note: Potential inclusion of patients with progression, which was not
determined or confirmed by RECISTv1.1 (e.g., bone only disease), must be
discussed and approved by the Medical Monitor or Study Director.
5. Adequate laboratory parameters:
• Adequate hepatic function:
* AST, ALT and GGT within ULN, and Bilirubin within ULN for patients without
liver metastasis.
* AST, ALT and GGT <= 2.5 x ULN, and Bilirubin <= 1.5 x ULN for patients with
liver metastasis.
* Exception: Bilirubin <= 2.5 x ULN for patients who have known serum bilirubin
increases due to underlying Gilbert*s Syndrome or familial benign unconjugated
hyperbilirubinemia.
- Note: As transient elevations in GGT can occur due to nonhepatobiliary
etiologies, the test can be repeated during Screening after consultation with
the
Medical Monitor.
• Adequate renal function: Creatinine clearance >= 50 mL/min.
• Adequate hematologic function: Absolute neutrophil count (ANC) >= 1500
cells/µL, Platelet count >= 100,000/µL and Hemoglobin >= 8.0 g/dL.
• Coagulation tests: Activated partial thromboplastin time (aPTT) <= 1.5 x ULN
and international normalized ratio (INR) <= 1.7 without anti-coagulants.
* Protocol only requires to test for standard coagula

Exclusion Criteria

Patients will be excluded from the study if one or more of the following
criteria is/are applicable:
1. Any prior exposure to DR5 agonists.
2. Receipt of any anti-cancer therapy (including investigational agents) within
4 weeks or within 5 half-lives prior to the first dose of study treatment,
whichever is shorter.
• Note: patients who received pazopanib as an immediate prior line, must have a
4 week washout and no evidence of prior or residual hepatotoxicity.
• Note: patients with any history or evidence of Grade >=3 hepatotoxicity on
prior anti cancer therapy are excluded.
3. Receipt of radiotherapy (with the exception of palliative localized
radiation) within 4 weeks to the first dose of study treatment. Patients must
have recovered from all radiation-related toxicities and not require
corticosteroids.
• Note: A 1-week washout is required for palliative radiation to non-central
nervous system (CNS) disease.
• Note: patients who had prior radiotherapy involving the liver (total
calculated dose to the liver >10Gy) are excluded.
4. Receipt of liver-directed therapies (e.g., RFA, TACE/embolization,
cryotherapy, SBRT, or others) within 12 months prior to the first dose of study
treatment.
• Note: patients who had prior radioembolization with Yttrium-90 beads are
excluded.
5. Allergy or sensitivity to INBRX-109 or known allergies to Chinese hamster
ovary (CHO) cell-produced antibodies, which in the opinion of the investigator
suggest an increased potential for an adverse hypersensitivity to INBRX-109.
6. Non-conventional CS, e.g., clear-cell, mesenchymal, extraskeletal myxoid,
myxoid*, and dedifferentiated CS.
• Note: *Conventional CS with myxoid features are considered Grade 2
conventional CS and are allowed in this study.
7. Prior or concurrent malignancies.
• Exception: Patients with a prior or concurrent malignancy whose natural
history or treatment does not have the potential to interfere with the safety
or efficacy assessments of INBRX-109. These cases must be reviewed and
discussed with the medical monitor and sponsor for potential inclusion.
8. Symptomatic active CNS metastases or leptomeningeal disease.
• Exception: Patients with asymptomatic CNS metastases are eligible if
controlled, defined as >= 4 weeks of stable neurologic function following CNS
directed therapy (stereotactic radiotherapy, definitive surgical resection,
and/or whole brain radiotherapy); not requiring steroids; and no evidence of
CNS disease progression as determined by radiographic imaging within 4 weeks
prior to the first dose of study treatment.
• Note: Patients with spinal cord metastases are allowed.
• Note: Patients with untreated, uncontrolled, ongoing spinal cord compression
are excluded.
9. Chronic liver diseases including but not limited to NAFLD or NASH,
alcohol-related liver disease, cirrhosis, hemochromatosis, Wilson*s disease,
alpha-1 antitrypsin deficiency, liver hemangioma, hepatic or biliary autoimmune
disorders (e.g., primary biliary cholangitis, autoimmune hepatitis) ), history
of portal or hepatic vein thrombosis, sinusoidal occlusion syndrome.
• Note: Liver imaging is required for all patients to rule out chronic liver
diseases. When NAFLD, NASH, fibrosis, or cirrhosis are suspected, liver MRI or
MRE are preferred, and the percentage of liver fat cont

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Endpoint:<br /><br>Progression free survival per RECISTv1.1 assessed by central real-time<br /><br>independent radiology review (IRR) in the intend-to-treat (ITT) population is<br /><br>the primary endpoint.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Endpoints include overall survival, objective response rate,<br /><br>progression free survival by Investigator assessment, Quality of Life, disease<br /><br>control rate, duration of response, safety, pharmacokinetics and immunogenicity.<br /><br><br /><br>Predictive Biomarker Strategy:<br /><br>Assessment of potential predictive diagnostic biomarkers for INBRX-109 is an<br /><br>exploratory endpoint, and availability of archival tissue or a fresh cancer<br /><br>biopsy is mandatory for enrollment to this study.</p><br>