CLINICAL TRIAL / NCT03715933
Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas
- Interventional
- Recruiting
- NCT03715933
Contact Information
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
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).
Gender
All
Age Group
12 Years to 85 Years
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Males or females aged ≥12 to <85 years for Ewing sarcoma and 18 to <85 years of age
for GIST.
- Escalation: Histologically or cytologically-confirmed advanced/metastatic or
non-resectable solid tumors, including sarcoma, that are refractory or intolerant to
standard therapy, or for which no standard therapy exists that is likely to confer
any clinical benefit.
- Expansion Cohorts: Malignant pleural mesothelioma, gastric adenocarcinoma,
colorectal adenocarcinoma, pancreatic adenocarcinoma and certain sarcoma subtypes
(e.g., chondrosarcoma, Ewing sarcoma), GIST, and SDH-def solid tumors with locally
advanced or metastatic, non-resectable disease, that are refractory or intolerant to
standard therapy, or for which no standard therapy exists that is likely to confer
any clinical benefit.
- Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma)
criteria.
- Adequate hematologic, coagulation, hepatic and renal function as defined per
protocol.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 for Part 1
and ECOG PS of 0, 1 or 2 for Parts 2 and 3.
Exclusion Criteria:
- Prior treatment with or exposure to DR5 agonists.
- 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.
- 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.
- Subject has undergone allogeneic hematopoietic stem cell or bone marrow
transplantation within the last 5 years. Exception: Participants 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).
- Prior or concurrent malignancies. Exception: Subjects 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.
- Hematologic malignancies.
- Symptomatic active primary CNS tumors, leptomeningeal disease, and CNS metastases.
Exceptions per protocol.
- Chronic liver disease including but not limited to cirrhosis, non-alcoholic fatty
liver disease (NAFLD) or non-alcoholic 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. Exceptions per protocol.
- Acute viral or toxic liver disease within 12 months prior to the first dose of study
drug.
- Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus
(HIV) infection.
- Clinically significant cardiac condition, including myocardial infarction,
uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart
disease < 3 months;
- Sensitivity or contraindications to INBRX-109, irinotecan, or temozolomide.
- Major surgery within 4 weeks prior to enrollment on this trial.
- Systemic infection requiring antibiotics within 2 weeks prior to the first dose of
study drug.
- Pregnant or nursing females.
- 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.
- Gastric Cancer
- Sarcomas
- Solid Tumors