Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03715933
• Other study ID #: Ph1 INBRX-109
• Status: Recruiting
• Phase: Phase 1
• Start date: October 10, 2018
• Est. completion date: July 2026

Study information

• Verified date: April 2024
• Source: Inhibrx, Inc.
• Contact: Study Director, -Inhibrx
• Phone: 858-500-7833
• Email: clinicaltrials[@]inhibrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: July 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Chondrosarcoma
• Colorectal Adenocarcinoma
• Ewing Sarcoma
• Gastric Adenocarcinoma
• GIST
• Malignant Pleural Mesothelioma
• Mesothelioma
• Mesothelioma, Malignant
• Neoplasms
• Pancreatic Adenocarcinoma
• Sarcoma
• Sarcoma, Ewing
• Solid Tumors

Intervention

Drug:
• INBRX-109
Tetravalent DR5 Agonist Antibody
• Carboplatin
Chemotherapy
• Cisplatin
Chemotherapy
• Pemetrexed
Chemotherapy
• 5-fluorouracil
Chemotherapy
• Irinotecan
Chemotherapy
• Temozolomide
Chemotherapy

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Center for Cancer Research at NCI	Bethesda	Maryland
United States	The University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	City of Hope	Duarte	California
United States	NEXT Oncology - Virginia	Fairfax	Virginia
United States	START Midwest Michigan, PC	Grand Rapids	Michigan
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Vanderbilt University School of Medicine	Nashville	Tennessee
United States	David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	NEXT Oncology	San Antonio	Texas
United States	University of California, San Diego (UCSD) - Moores Cancer Center	San Diego	California
United States	Sarcoma Oncology Center	Santa Monica	California
United States	HonorHealth Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Inhibrx, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Anti-tumor activity of INBRX-109	Tumor response will be determined by RECISTv1.1.	Up to 2 years
Primary	Frequency and severity of adverse events of INBRX-109	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.	Up to 2 years
Primary	Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-109	The MTD and/or RP2D of INBRX-109 will be determined.	Up to 2 years
Secondary	Area under the serum concentration time curve (AUC) of INBRX-109	Area under the serum concentration time curve (AUC) of INBRX-109 will be determined.	Up to 2 years
Secondary	Immunogenicity of INBRX-109	Frequency of ant-drug antibodies (ADA) against INBRX-109 will be determined.	Up to 2 years
Secondary	Maximum observed serum concentration (Cmax) of INBRX-109	Maximum observed serum concentration (Cmax) of INBRX-109 will be determined.	Up to 2 years
Secondary	Trough observed serum concentration (Ctrough) of INBRX-109	Trough observed serum concentration (Cmax) of INBRX-109 will be determined.	Up to 2 years
Secondary	Time to Cmax (Tmax) of INBRX-109	Time to Cmax (Tmax) of INBRX-109 will be determined.	Up to 2 years