An Open-Label, Multicenter, First-in-Human, Phase 1 Dose-Escalation and Multicohort Expansion Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas

Trial ID: NCT03715933

Interventional - Phase 1 - Recruiting

This is a first-in-human, open-label, non-randomized, three-part phase 1 trial of INBRX-109, which is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5).

Conditions

• Ewing Sarcoma
• Colorectal Adenocarcinoma

Interventions

• INBRX-109
• Irinotecan
• Temozolomide
• carboplatin
• pemetrexed
• Leucovorin
• Fluorouracil
• Bevacizumab
• Trifluridine + Tipiracil

Eligibility

Inclusion criteria

• 1. Males or females aged ≥12 to less than 85 years for Ewing sarcoma and 18 to less than 85 years of age for other tumors.
• 2. Part 3 combination therapy expansion tumor types:
• Histologically confirmed Ewing sarcoma with a classical fusion: Patients with locally advanced or metastatic, unresectable, 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.
• Colorectal adenocarcinoma: Patients who have failed 1 (one) prior line of systemic therapy that did not include irinotecan.
• Colorectal adenocarcinoma: Patients who have failed 2 but no more than 3 prior lines of systemic therapy and are FTD/TPI-naïve.
• 3. Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma) criteria.
• 4. Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
• 5. 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 less than 16 years).
• 6. Estimated life expectancy of at least 12 weeks.
• 7. Availability of archival tissue or fresh cancer biopsy are mandatory.

Exclusion criteria

• 1. Prior treatment with or exposure to DR5 agonists.
• 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. Exceptions per protocol.
• 3. Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
• 4. Receipt of radiotherapy within 4 weeks prior to the first dose of study treatment, and liver-directed within 12 months prior to the first dose of study drug.
• 5. Subject has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. Exceptions per protocol.
• 6. Prior or concurrent malignancies. Exceptions per protocol.
• 7. Hematologic malignancies.
• 8. Symptomatic active primary CNS tumors, leptomeningeal disease, and CNS metastases. Exceptions per protocol. Patients with any evidence or history of multiple sclerosis (MS) or other demyelinating disorders are excluded.
• 9. Chronic liver diseases including fatty liver. Exception: Patients \< 45 years old with fatty liver disease may be accepted as long as adequate hepatic function as defined in the inclusion/exclusion criteria is confirmed.
• 10. Acute viral or toxic liver disease within 12 months prior to the first dose of study drug.
• 11. Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
• 12. Known sensitivity or contraindications to the following drugs:
• Ewing sarcoma: irinotecan or TMZ
• colorectal adenocarcinoma: FU, leucovorin, irinotecan, bevacizumab or FTP/TPI
• 13. Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease less than 3 months prior to enrollment.
• 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 on this trial.
• 16. Systemic infection requiring antibiotics within 2 weeks prior to the first dose of study drug.
• 17. Other exclusion criteria per protocol.

Sponsor

Inhibrx Biosciences, Inc

Source: ClinicalTrials.gov

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