OZEKIBART for Ewing sarcoma | Colorectal adenocarcinoma | Gastrointestinal stromal tumor | SDH-deficient solid tumors | Advanced or metastatic solid tumors

Inclusion criteria

• {"criterion_text":"- 1. Males or females aged ≥12 to <85 years of age for Ewing sarcoma and 18 to <85 years of age for other tumors. Note: body weight for adolescent patients must be ≥30 kg. Note: Study sites in the Netherlands are only allowed to enroll patients ≥16 years of age."}
• {"criterion_text":"- 9. Estimated life expectancy, in the documented judgment of the Investigator, of at least 12 weeks."}
• {"criterion_text":"- 10.\tFertile 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. Fertile male patients with female partners of childbearing potential must be willing to use acceptable methods of contraception at least 28 days before the first dose of study treatment until at least 3 months after the last dose of study treatment. Female patients of childbearing potential must be willing to use acceptable methods of contraception at least 28 days before the first dose of study treatment until at least 6 months after the last dose of TMZ or irinotecan, or at least 3 months after the last dose of INBRX 109, whichever is later. Male patients must refrain from donating sperm during this period. a.\tA woman is considered of childbearing potential following menarche and until becoming post menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Postmenopausal state is defined as no menses for 12 months without an alternative medical cause. b.\tA man is considered fertile after puberty unless permanently sterile by bilateral orchiectomy."}
• {"criterion_text":"- 11. Recovery from all reversible AEs of previous anticancer therapies to Baseline or NCI CTCAE v5.0 Grade 1 or better. Inclusion of patients with other not clinically significant toxicities (eg, alopecia [any Grade] and Grade ≤2 sensory peripheral neuropathy, vitiligo, electrolyte abnormalities, lymphopenia) should be discussed with the Medical Monitor or Study Director."}
• {"criterion_text":"- 12. Ability to understand and the willingness to sign a written informed consent/assent document, which must be obtained prior to initiation of any study procedures."}
• {"criterion_text":"- 2. Tumor types and tissue availability: 2a. Histologically confirmed Ewing sarcoma with a classical fusion. - Patients with locally advanced or metastatic, unnresectable, relapsed, or refractory disease who have received at least 1 but no more than 2 prior lines of systemic treatment and who are candidates for irinotecan and TMZ regimens. Prior systemic therapy in adjuvant or neoadjuvant (definitive) setting is allowed. - Patients with documented disease progression within 6 months of completion of their adjuvant or neoadjuvant therapy are considered primary refractory in the front-line setting. - Patients need to have documented presence of EWSR1-FLI1 (or EWSR1-ERG, EWSR1-FEV) rearrangement, which must be confirmed by a local institutional pathology laboratory or reference laboratory pathology review. - Submission of archival tissue is required for enrollment. For patients who do not have archival tissue available, a fresh biopsy will be necessary."}
• {"criterion_text":"- 2b: Colorectal adenocarcinoma. o\tPatients with locally advanced or metastatic, unresectable disease, who have received at least 2, but no more than 3 prior lines of systemic therapy. o\tPrevious treatment with an irinotecan-containing regimen is allowed but not as an immediate prior line of therapy (ie, patients had to receive a non irinotecan based treatment regimen before entering the study). o\tSubmission of archival tissue is required for enrollment. For patients who do not have archival tissue available, a fresh biopsy will be necessary"}
• {"criterion_text":"- 3. Measurable disease, as defined by RECIST version 1.1 or modified RECIST criteria. 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."}
• {"criterion_text":"- 4. Adequate hepatic function, defined by the following: •\tPatients without liver metastasis: a.\tAST and ALT within the upper limit of normal (ULN), gamma-glutamyl transferase (GGT) ≤1.5 × ULN and b.\tBilirubin within ULN. •\tPatients with liver metastasis: a.\tAST, ALT, and GGT ≤2.5 × ULN, and b.\tBilirubin ≤1.5 × ULN. •\tException: Bilirubin ≤2.5 × ULN is allowed for patients who have known serum bilirubin increases due to underlying Gilbert’s syndrome or familial benign unconjugated hyperbilirubinemia. o\tBecause Gilbert’s syndrome is associated with a mutation in uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene, any patient with Ewing sarcoma with known history of this syndrome must be screened for UGT1A1 gene variant. If needed, the dose of irinotecan should be adjusted."}
• {"criterion_text":"- 5.\tAdequate renal function: •Estimated creatinine CL ≥30 mL/min in Part 3 Cohort C3 and ≥50 mL/min in Part 3 Cohort C4 calculated using Schwartz’s formula (for patients ≤18 years) or Cockcroft Gault formula (for patients >18 years)"}
• {"criterion_text":"- 6. Adequate hematologic function: - Absolute neutrophil count (ANC) ≥1,500 cells/μL. - Platelet count ≥100,000/μL. - Hemoglobin ≥8.0 g/dL."}
• {"criterion_text":"- 7. Coagulation tests: - Activated partial thromboplastin time (aPTT) ≤1.5 × ULN. - International normalized ratio (INR) ≤1.7 without anticoagulants. - Exception: INR 2 to ≤3 is acceptable for patients on anticoagulation."}
• {"criterion_text":"- 8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1, or Karnofsky Performance Status score of ≥60, or Lansky Play-Performance Scale for Children score ≥60 (for patients <16 years). Exception: inclusion of non-frail, physically active patients with compromised mobility due to prior cancer surgery (eg, limb amputation, hemipelvectomy) should be discussed with the Medical Monitor and/or Study Director."}

Exclusion criteria

• {"criterion_text":"- 1. Any prior treatment with or exposure to DR5 agonists."}
• {"criterion_text":"- 10.\tAcute viral liver desease (including hepatitis A, D, or E viruses [HAV, HDV, or HEV], cytomegalovirus [CMV], and Epstein Barr virus [EBV]) or toxic liver disease within 12 months prior to the first dose of study treatment."}
• {"criterion_text":"- 11. Any evidence or history of hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection. - Note: If test results for HBV and HCV infection are ≥1 month old or not available in the medical history, they must be confirmed by Baseline test result obtained during Screening. Test results for HIV do not need to be repeated."}
• {"criterion_text":"- 12. •\tCohort C3, with treatment with irinotecan and TMZ: a.\tKnown sensitivity to irinotecan or TMZ. b.\tAny contraindications to TMZ or irinotecan. •\tCohort C4, with treatment with FOLFIRI: a.\tKnown sensitivity to FU, leucovorin, or irinotecan. b.\tAny contraindications to FU, leucovorin, or irinotecan."}
• {"criterion_text":"- 13. Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease <3 months prior to enrollment; left ventricular ejection fraction (LVEF) <50% or shortening fraction <28% (echocardiogram is not required at Screening); New York Heart Association (NYHA) Class III or IV congestive heart failure; or uncontrolled hypertension Stage >1. Note: The NYHA classification does not apply to adolescent patients. Cardiac condition of adolescent patients should be assessed per institutional and/or national guidelines."}
• {"criterion_text":"- 14. Acute, hemodynamically significant deep vein thrombosis or clinically significant pulmonary embolism not resolved or stable for at least 3 months prior to the start of study treatment."}
• {"criterion_text":"- 15. Major surgery within 4 weeks prior to enrollment in this study."}
• {"criterion_text":"- 16.\tSystemic clinically significant bacterial, fungal, or viral infection requiring anti-infective treatment within 2 weeks prior to the first dose of study treatment."}
• {"criterion_text":"- 17.\tPregnant or nursing females; and female patients of childbearing potential and fertile male patients with female partners of childbearing potential unwilling use acceptable contraception methods as presented in inclusion criterion #10."}
• {"criterion_text":"- 18. Any known, documented, or suspected history of illicit substance abuse that would preclude patient from participation, unless clinically justified (ie, will not interfere with study participation and/or will not compromise study objectives) per judgment of the Investigator and with approval of the Medical Monitor or Study Director. •\tException: Physician-prescribed medicinal opioids or cannabinoids without hepatotoxic potential are allowed for pain management. Cannabinoids are allowed for patients from states/countries that have legalized its use. •\tNote: Patients with ongoing or prior history of alcoholism are excluded unless they qualify per LFTs and liver imaging."}
• {"criterion_text":"- 19.\tAny other disease or clinically significant abnormality in laboratory parameters, including serious medical or psychiatric illness/condition, which in the judgment of the Investigator likely might compromise the safety of the patient or integrity of the study, interfere with the patient participation in the study or compromise the study objectives. Note: Patients with the following ongoing comorbid conditions are excluded: a.\tClinically significant, uncontrolled with medication type 2 diabetes mellitus; metabolic syndrome or pre-diabetes; insulin-resistance (with A1c >6%). b.\tClinically significant, uncontrolled with medication hypothyroidism. c.\tClinically significant, uncontrolled with medication hypertriglyceridemia and/or hyperlipidemia. d.\tHypoxia with oxygen saturation <92%. e.\tEncephalopathy Stage ≥1. f.\tRecent or ongoing gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy)."}
• {"criterion_text":"- 2. Receipt of any anticancer therapy (including investigational agents) within 4 weeks or within 5 half lives prior to the first dose of study treatment. - Exception: Hormonal and/or hormonal replacement therapy. - 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 anticancer therapy are excluded."}
• {"criterion_text":"- 20. Patients who are receiving strong cytochrome P450 (CYP) 3A inhibitors and/or inducers, and/or UGT1A1 inhibitors within 14 days of Cycle 1 Day 1."}
• {"criterion_text":"- 3.\tAllergy or sensitivity to INBRX-109 or known allergies to Chinese hamster ovary (CHO) cell-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to INBRX-109."}
• {"criterion_text":"- 4.\tReceipt of radiotherapy (with the exception of palliative localized radiation, ie, 1 week) within 4 weeks prior to the first dose of study treatment, and liver-directed therapies within 12 months prior to the first dose of study treatment. Patients must have recovered from all radiation-related toxicities and not require corticosteroids. o Note: 1-week washout is required for palliative radiation to non-central nervous system (CNS) disease. o\tNote: Patients who had prior radioembolization with Yttrium-90 beads are excluded. o\tNote: Patients who had prior radiotherapy involving liver (total calculated dose to the liver ≥10 Gy) are excluded."}
• {"criterion_text":"- 5. Has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. - Exception: Patients who have had a stem cell or bone marrow transplant >5 years ago are eligible for enrollment, as long as there are no symptoms of graft versus host disease (GVHD)."}
• {"criterion_text":"- 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 of INBRX-109. These cases must be reviewed and discussed with the Medical Monitor or Study Director for potential inclusion."}
• {"criterion_text":"- 7. Hematologic malignancies (ie, acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], myelodysplastic syndrome [MDS], CLL, chronic myelogenous leukemia [CML], non Hodgkin lymphoma [NHL], Hodgkin lymphoma, and multiple myeloma)."}
• {"criterion_text":"- 8. Symptomatic active primary CNS tumors, leptomeningeal disease, and CNS metastases. - Exception: Patients with asymptomatic CNS metastases are eligible if there is 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. - Note: Patients with any evidence or history of multiple sclerosis (MS) or other demyelinating disorders are excluded."}
• {"criterion_text":"- 9.\tAny chronic liver disease including but not limited to cirrhosis, nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), alcohol related liver disease, hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, multiple liver hemangioma (except incidental finding of clinically nonsignificant liver hemangioma), hepatic or biliary autoimmune disorders (ie, primary biliary cholangitis, autoimmune hepatitis), history of portal or hepatic vein thrombosis, and sinusoidal occlusion syndrome. o\tNote: Patients with any imaging evidence of NAFLD, NASH, fibrosis, or cirrhosis, regardless of prior history and liver function tests (LFTs) at Baseline are excluded from the study. Liver magnetic resonance imaging (MRI) or magnetic resonance elastography (MRE) are preferred. Other imaging modalities, such as computed tomography (CT; without contrast), ultrasound, transient elastography, are acceptable to rule out other chronic liver diseases. o\tException: 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. Unclear cases must be reviewed and discussed with the Medical Monitor or Study Director for potential inclusion. o\tNote: Patients aged >45 years with NAFLD are excluded from the study. o Patients aged >65 years and with BMI >30 kg/m2 are excluded from the study. Patients aged ≥45 years with hepatic steatosis index (HSI) ≥36 and fatty liver index (FLI) ≥60 are also excluded from the study. If one of the values (HSI or FLI) is in the acceptable range and the other is above the cutoff, the patient may still be eligible for the study if fatty liver is excluded at imaging. These cases must be reviewed and discussed with the Medical Monitor."}

Primary endpoints

• {"endpoint_text":"- 1. TEAEs including determination of DLTs and SAEs. AEs will be assessed, and severity assigned by using the NCI CTCAE v5.0.","definition_or_measurement_approach":"AEs assessed and severity assigned using NCI CTCAE v5.0; includes determination of dose-limiting toxicities (DLTs) and serious adverse events (SAEs)."}
• {"endpoint_text":"- 2. Clinical response including ORR and DOR per RECIST v1.1 in colorectal adenocarcinoma and Ewing sarcoma.","definition_or_measurement_approach":"Objective response rate (ORR) and duration of response (DOR) assessed per RECIST v1.1 in colorectal adenocarcinoma and Ewing sarcoma."}

Secondary endpoints

• {"endpoint_text":"- 1. PK parameters: AUC0-inf, AUC0-last, AUC0-21d or AUC0-28d (depending on dosing interval), Cmax, Ctrough, and Tmax will be estimated using standard non compartmental analysis (NCA) as the data allow. Other PK parameters (λz, t½, Vd, CL, and accumulation ratios [RCmax, RCtrough]) will be calculated if data permit.","definition_or_measurement_approach":"Pharmacokinetic parameters estimated using standard non-compartmental analysis (NCA); specific parameters include AUC0-inf, AUC0-last, interval-specific AUC, Cmax, Ctrough, Tmax, and others (λz, t½, Vd, CL, accumulation ratios) if data permit."}
• {"endpoint_text":"- 2. Incidence, quantity, and effect of ADAs against INBRX-109.","definition_or_measurement_approach":"Anti-drug antibodies (ADAs) incidence, titer/quantity and impact on safety/PK/efficacy to be measured (immunogenicity assessments)."}
• {"":"","endpoint_text":"- 3. Median PFS (colorectal adenocarcinoma and Ewing sarcoma).","definition_or_measurement_approach":"Median progression-free survival measured per study radiographic and clinical assessment schedules (PFS defined as time from treatment start to progression or death)."}

Netherlands

Earliest CTIS Part Ii Submission Date

03-04-2024

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

674

Number Of Sites

2

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

03-04-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

679

Number Of Sites

3

Number Of Participants

7

Spain

Earliest CTIS Part Ii Submission Date

01-04-2024

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

689

Number Of Sites

3

Number Of Participants

10

France

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

05-02-2026

Processing Time Days

720

Number Of Sites

2

Number Of Participants

10

Primary sponsor

Full Name

Inhibrx Biosciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

8

Name

Q Squared Solutions Limited

Responsibilities

15: Kits for PK/ADA, collects samples

Name

Q Squared Solutions Holdings LLC

Responsibilities

15: Kits for PK/ADA, collects samples.

Third parties

• {"country":"United Kingdom","full_name":"Catalent Cts (Edinburgh) Limited","duties_or_roles":"14; 15: Labelling and packaging, QP release for UK","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"15: Kits for PK/ADA, collects samples","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"8","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Precision for Medicine GmbH","duties_or_roles":"15: kits for tissue, collects the tissue for EU","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"14; 15: QP release for EU","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"15: Scan images via portal","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions Holdings LLC","duties_or_roles":"15: Kits for PK/ADA, collects samples.","organisation_type":"Laboratory/Research/Testing facility"}