Study of INBRX-109 in Conventional Chondrosarcoma

Study Overview
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Brief Summary
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Randomized, blinded, placebo-controlled, Phase 2 study of INBRX-109 in unresectable or metastatic conventional chondrosarcoma patients.

Detailed Description
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This is a randomized, blinded, placebo-controlled, Phase 2 study of INBRX-109 in unresectable or metastatic conventional chondrosarcoma patients. INBRX-109 is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5).

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

Conditions
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Conventional Chondrosarcoma

Intervention / Treatment
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* Drug: INBRX-109
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Conventional chondrosarcoma, unresectable (=inoperable) or metastatic. 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. Radiologic progression of disease per RECISTv1.1 criteria within 6 months prior to screening for this study. Adequate hematologic, coagulation, hepatic and renal function as defined per protocol. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Estimated life expectancy of at least 12 weeks. Availability of archival tissue or fresh cancer biopsy are mandatory. Exclusion Criteria: Any prior exposure to DR5 agonists. Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies. Non-conventional chondrosarcoma, e.g., clear-cell, mesenchymal, extraskeletal myxoid, myxoid, and dedifferentiated chondrosarcoma. 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. Chronic liver diseases. Exception: Patients with fatty liver disease are acceptable as long as adequate hepatic function as defined in the inclusion/exclusion criteria is confirmed. Evidence or history of multiple sclerosis (MS) or other demyelinating disorders. Other exclusion criteria per protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: INBRX-109 and placebo arms are in parallel. Patients on placebo are allowed to cross-over to open-label INBRX-109 at time of disease progression.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INBRX-109<br>IV every three weeks | Drug: INBRX-109<br>* Tetravalent DR5 Agonist Antibody<br>|
| Placebo Comparator: Placebo<br>IV every three weeks | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival per RECISTv1.1 comparing INBRX-109 and placebo | Progression-free survival per RECISTv1.1 will be determined. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival of patients comparing INBRX-109 and placebo | Overall Survival in the ITT population | 3 years | 
| Overall response rate (in percent), duration of response (in time) and disease control rate (in percent) | Tumor response will be determined by RECISTv1.1. | 3 years | 
| PFS per RECISTv1.1 by Investigator assessment | PFS per RECISTv1.1, by Investigator assessment, comparing INBRX-109 and placebo. | 3 years | 
| Quality of life assessed by EORTC questionnaire for cancer patients (QLQ-C30) comparing INBRX-109 and placebo | Quality of life will be determined. | 3 years | 
| DCR per RECISTv1.1 by real-time IRR | measured by DCR per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo | 3 years | 
| DOR per RECISTv1.1 by real-time IRR | evaluate duration of response (DOR) per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo | 3 years | 
| To evaluate the safety and tolerability of INBRX-109 | Adverse events will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. | 3 years | 
| Characterize the pharmacokinetics of INBRX-109. | AUC0-inf, AUC0-last, AUC0-21d, Cmax, Ctrough, Tmax will be estimated using a standard non- Sponsor: Inhibrx, Inc. Version 5.0 (Amendment 4) Protocol Number: Ph2 INBRX-109 SA CS 28-Feb-2023 Page 41 of 113 CONFIDENTIAL Objective Endpoint compartmental method as the data allow. Other PK parameters (λz, t1/2, Vd, CL, and accumulation ratios RCmax, RCtrough) | 3 years | 
| Immunogenicity of INBRX-109 | Frequency of anti-drug antibodies against INBRX-109 will be determined. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DR5, INBRX-109, Apoptosis, Programmed cell death