E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable or metastatic conventional chondrosarcoma |
|
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. |
|
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) |
|
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 RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo. |
|
E.2.2 | Secondary objectives of the trial |
• Evaluate the anticancer efficacy of INBRX-109 as measured by overall survival (OS) comparing INBRX-109 and placebo. • Evaluate the anticancer efficacy of INBRX-109 as measured by PFS per RECISTv1.1, by Investigator assessment, comparing INBRX-109 and placebo. • Evaluate the quality of life (QoL) as measured by EORTC QLQ-C30, EQ-5D-5L, PGI-C and PGI-S comparing INBRX-109 and placebo. • Evaluate the 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. • Evaluate the anticancer efficacy of INBRX-109 as measured by DCR per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo. • Evaluate the safety and tolerability of INBRX-109 • Characterize the pharmacokinetics (PK) of INBRX-109 • Evaluate the frequency of ADA, and neutralizing ADA (NAb), against INBRX-109 and to explore the potential relationship with safety, PK and efficacy of INBRX-109
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females aged ≥ 18 years 2. Conventional chondrosarcoma, unresectable (i.e., resection with curative intent to remove cancer completely is not possible) ) 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. Radiologic progression of disease 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. Male and female patients of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception (i.e., less than 1% failure rate), from the time of signing informed consent and for the duration of study participation through 3 months, following the last dose of study treatment. |
|
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 investigational or approved anticancer drug(s) including biological product(s) within 4 weeks or within 5 half-lives, whichever is longer, prior to the first dose of study treatment. 4. Non-conventional chondrosarcoma, e.g., clear-cell, mesenchymal, extraskeletal myxoid, myxoid, and dedifferentiated chondrosarcoma. 5. 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. 6. Chronic liver diseases. Exception: Patients aged < 64 years with NAFLD detected by imaging are acceptable 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. 7. Patients aged > 65 years and with BMI > 30 kg/m2 are excluded from the study. 8. Other exclusion criteria per protocol. |
|
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
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From study start until the end of the study. |
|
E.5.2 | Secondary end point(s) |
• Overall Survival (OS) • Progression Free Survival (PFS) per RECISTv1.1 by Investigator assessment • Quality of Life (QoL) per EORTC QLQ-C30, EQ-5D-5L, PGI-C, PGI-S • Objective Response Rate (ORR) and Duration of Response (DOR) per RECISTv1.1 by real-time Independent Radiology Review (IRR) • Disease Control Rate (DCR) 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)
|
|
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
|
|
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.8.5 | 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 |
Germany |
Ireland |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
France |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |