Study of INBRX-109 in Patients with Advanced Solid Tumors, Including Sarcomas.
- Conditions
- Advanced or metastatic solid tumorsTherapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-508139-29-00
- Lead Sponsor
- Inhibrx Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 130
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 must be =30 kg., 9. Estimated life expectancy, in the documented judgment of the Investigator, of at least 12 weeks., 10. 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. Male patients must refrain from donating sperm during this period. a. A 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. A man is considered fertile after puberty unless permanently sterile by bilateral orchiectomy., 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., 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., 2. Tumor types and tissue availability: 2a. Histologically confirmed Ewing sarcoma. - Patients with locally advanced or metastatic, nonresectable disease, relapsed, or refractory disease who have received at least 1 but no more than 2 prior lines of systemic treatment with a preferred first-line chemotherapy regimens, 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 other less common 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., 2b. SDH-deficient solid tumors or GIST with recurrent or refractory, unresectable, or metastatic disease for which there is no known curative therapy. - Eligible patients must have documented loss of SDHB expression by IHC and/or assessment of SDH (A/B/C/D) gene mutation(s) by next generation sequencing using certified assays. - Patients with GIST must have pathologically confirmed disease. - Previously untreated patients are eligible, due to the absence of approved standard systemic therapy. - Patients previously treated with other therapies for GIST will also be eligible. - Submission of archival tissue is required for enrollment., 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 progres
1. Any prior treatment with or exposure to DR5 agonists., 10. Acute viral (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 drug., 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., 12. - Cohort C3, with treatment with irinotecan and TMZ: a. Known sensitivity to irinotecan or TMZ. b. Any contraindications to TMZ or irinotecan. - Cohort C5, with treatment with TMZ: a. Any history of prior Grade =3 toxicity to TMZ. b.Known sensitivity to TMZ. c. Any contraindications to TMZ., 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., 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., 15. Major surgery within 4 weeks prior to enrollment in this study., 16. Systemic clinically significant bacterial, fungal, or viral infection requiring anti-infective treatment within 2 weeks prior to the first dose of study drug., 17. Pregnant or nursing females; and female patients of childbearing potential and fertile male patients with female partners of childbearing potential unwilling use acceptable contraception methods at least 28 days before the first dose of study treatment until 90 days after the last dose of study treatment., 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. •Exception: 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. •Note: Patients with ongoing or prior history of alcoholism are excluded unless they qualify per LFTs and liver imaging., 19. Any 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 clinically significant comorbid conditions are excluded: a. Uncontrolled type 2 diabetes mellitus; metabolic syndrome or pre-diabetes; insulin-resistance (with A1c >6%). b. Unc
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and tolerability of INBRX-109 administered IV in combination with distinct chemotherapies in adults and/or adolescents with advanced/metastatic Ewing sarcoma and SDH-deficient solid tumors or GIST, and to assess the antitumor efficacy in Ewing sarcoma by objective response rate (ORR) and duration of response (DOR).;Secondary Objective: 1. To assess the PK of INBRX-109 in combination with distinct chemotherapies., 2. To assess the immunogenicity of INBRX-109 in combination with distinct chemotherapies., 3. To assess median progression-free survival (PFS) in Ewing sarcoma.;Primary end point(s): 1. TEAEs including determination of DLTs and SAEs. AEs will be assessed, and severity assigned by using the NCI CTCAE v5.0., 2. Clinical response including ORR and DOR per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Ewing sarcoma only.
- Secondary Outcome Measures
Name Time Method Secondary end point(s):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 (?z, t½, Vd, CL, and accumulation ratios [RCmax, RCtrough]) will be calculated if data permit.;Secondary end point(s):2. Incidence, quantity, and effect of ADAs against INBRX-109.;Secondary end point(s):3. PFS (Ewing sarcoma).