E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable or metastatic conventional chondrosarcoma |
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E.1.1.1 | Medical condition in easily understood language |
Malignant bone tumor that cannot be resected or it has been spread from the primary site (place where it started) to other places in the body. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008734 |
E.1.2 | Term | Chondrosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the anticancer efficacy of INBRX-109 in the Intention To Treat (ITT) population as measured by Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECISTv1.1), assessed by central real-time IRR, comparing INBRX-109 and placebo. |
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E.2.2 | Secondary objectives of the trial |
Evaluate: • Anticancer efficacy of INBRX-109 as measured by overall survival (OS) comparing INBRX-109 and placebo. • Anticancer efficacy of INBRX-109 as measured by objective response rate (ORR) per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo • Anticancer efficacy of INBRX-109 as measured by PFS per RECISTv1.1, by Investigator assessment, comparing INBRX-109 and placebo • QoL, as measured by EORTC QLQ-C30, Pain and Physical Functioning scales, comparing INBRX-109 and placebo • Anticancer efficacy of INBRX-109 as measured by DCR per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo • DOR per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo. • Safety and tolerability of INBRX-109 • Characterize the pharmacokinetics (PK) of INBRX-109 • Frequency of ADA, and neutralizing ADA (NAb), against INBRX-109 and to explore the potential relationship with safety, PK and efficacy of INBRX-109
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females aged ≥ 18 years to ≤ 85 years 2. Conventional chondrosarcoma, unresectable (i.e., not amenable to tumor resection with curative intent) or metastatic. 3. Measurable disease by RECISTv1.1. Note: Tumor lesions 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 treatment. 4. Evidence of confirmed radiographic disease progression per RECISTv1.1 criteria within 6 months prior to screening for this study. 5. Adequate hematologic, coagulation, hepatic and renal function as defined per protocol. 6. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. 7. Estimated life expectancy of at least 12 weeks. 8. Fertile male patients with female partners of childbearing potential and female patients of childbearing potential must agree to avoid impregnating a partner or becoming pregnant, respectively. They must be willing to use acceptable methods of contraception at least 28 days before the first dose of study treatment until 90 days after the last dose of study treatment. |
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E.4 | Principal exclusion criteria |
1. Any prior exposure to DR5 agonists. 2. Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies. 3. 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 longer for biologics, and 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. 4.Receipt of radiotherapy (with the exception of palliative localized radiation) within 4 weeks to the first dose of study treatment. Participants must have recovered from all radiation-related toxicities and not require corticosteroids. Note: 1-week washout is required for palliative radiation to non-CNS disease. Note: patients who had prior radiotherapy involving the liver (total calculated dose to the liver >10Gy) are excluded. 5. Non-conventional chondrosarcoma, e.g., clear-cell, mesenchymal, extraskeletal myxoid, myxoid, and dedifferentiated chondrosarcoma. 6. 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. 7. Chronic liver diseases including but not limited to non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (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: Patients with any imaging evidence of NAFLD, NASH, fibrosis, or cirrhosis, regardless of prior history and LFTs at baseline are excluded from the study (liver MRI or MRE are preferred, other imaging modalities, such as CT [with contrast], ultrasound, transient elastography, are acceptable). Exception: Patients aged < 45 years with NAFLD detected by imaging may participate in the study if adequate hepatic function as defined in the inclusion criteria is confirmed. Note: Patients aged > 65 years with non-alcoholic fatty liver disease (NAFLD) are excluded from the study. Note: Patients aged > 65 ≥45 years with NAFLD are excluded from the study. 8. Patients aged ≥ 65 years and with BMI ≥ 30 kg/m2 and/or patients aged ≥45 years with HSI ≥36 or FLI ≥60 are excluded from the study. 9. Any evidence or history of multiple sclerosis (MS) or other demyelinating disorders. 10. Other exclusion criteria per protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Progression Free Survival (PFS) per RECISTv1.1 assessed by central IRR in the ITT population
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From study start until the end of the study. |
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E.5.2 | Secondary end point(s) |
• Overall Survival (OS) • Objective Response Rate (ORR) per RECISTv1.1 by real-time Independent Radiology Review (IRR) • Progression Free Survival (PFS) per RECISTv1.1 by Investigator assessment • Quality of Life (QoL) per EORTC QLQ-C30 (Pain and Physical function) • Disease Control Rate (DCR) per RECISTv1.1 by real-time IRR • Duration of Response (DOR) per RECISTv1.1 by real-time IRR • Treatment-Emergent Adverse Event (TEAEs) including SAEs • PK characterization: AUC0-inf, AUC0-last, AUC0-21d, Cmax, Ctrough, Tmax will be estimated using a standard non-compartmental method as the data allow. Other PK parameters (λz, t1/2, Vd, CL, and accumulation ratios RCmax, RCtrough) will be calculated if data permit • Frequency of Anti-Drug Antibodies (ADA) and neutralizing ADA (NAb)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• OS: from study start until the end of the study (EoS) • PFS: until DP • QoL: from study start until EoS • ORR and DOR per RECISTv1.1 by IRR: until Disease Progression (DP) • DCR: until DP • TEAEs including SAEs: from study start until EoS. • PK characterization: from study start until EoS • ADA and NAb: from study start until EoS
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Korea, Republic of |
United Kingdom |
United States |
France |
Germany |
Ireland |
Italy |
Netherlands |
Spain |
Türkiye |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |