Detailed Description:
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).
Inclusion Criteria:
1. Conventional chondrosarcoma, unresectable (=inoperable) or metastatic.
2. 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.
3. Radiologic progression of disease per RECISTv1.1 criteria within 6 months prior to
screening for this study.
4. Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
5. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
6. Estimated life expectancy of at least 12 weeks.
7. Availability of archival tissue or fresh cancer biopsy are mandatory.
Exclusion Criteria:
1. Any prior exposure to DR5 agonists.
2. Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
3. Non-conventional chondrosarcoma, e.g., clear-cell, mesenchymal, extraskeletal myxoid,
myxoid, and dedifferentiated chondrosarcoma.
4. 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.
5. 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.
6. Evidence or history of multiple sclerosis (MS) or other demyelinating disorders.
7. Other exclusion criteria per protocol.
Primary outcome:
1. Progression-free survival per RECISTv1.1 comparing INBRX-109 and placebo (Time Frame - 3 years):
Progression-free survival per RECISTv1.1 will be determined.
Secondary outcome:
1. Overall survival of patients comparing INBRX-109 and placebo (Time Frame - 3 years):
Overall Survival in the ITT population
2. Overall response rate (in percent), duration of response (in time) and disease control rate (in percent) (Time Frame - 3 years):
Tumor response will be determined by RECISTv1.1.
3. PFS per RECISTv1.1 by Investigator assessment (Time Frame - 3 years):
PFS per RECISTv1.1, by Investigator assessment, comparing INBRX-109 and placebo.
4. Quality of life assessed by EORTC questionnaire for cancer patients (QLQ-C30) comparing INBRX-109 and placebo (Time Frame - 3 years):
Quality of life will be determined.
5. DCR per RECISTv1.1 by real-time IRR (Time Frame - 3 years):
measured by DCR per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo
6. DOR per RECISTv1.1 by real-time IRR (Time Frame - 3 years):
evaluate duration of response (DOR) per RECISTv1.1, assessed by central real-time IRR, comparing INBRX-109 and placebo
7. To evaluate the safety and tolerability of INBRX-109 (Time Frame - 3 years):
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.
8. Characterize the pharmacokinetics of INBRX-109. (Time Frame - 3 years):
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)
9. Immunogenicity of INBRX-109 (Time Frame - 3 years):
Frequency of anti-drug antibodies against INBRX-109 will be determined.
- Experimental: INBRX-109
IV every three weeks - Placebo Comparator: Placebo
IV every three weeks
- INBRX-109:
Tetravalent DR5 Agonist Antibody - Placebo:
Placebo
Quelle: ClinicalTrials.gov
