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

April 24, 2024 updated by: Inhibrx, Inc.

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

240

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Active, not recruiting
        • HonorHealth Research Institute
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Principal Investigator:
          • Mark Agulnik, MD
        • Contact:
        • Contact:
      • Los Angeles, California, United States, 90067
      • San Diego, California, United States, 92093
        • Recruiting
        • University of California, San Diego (UCSD) - Moores Cancer Center
        • Principal Investigator:
          • Adam Burgoyne, MD
      • Santa Monica, California, United States, 90403
        • Recruiting
        • Sarcoma Oncology Center
        • Contact:
        • Principal Investigator:
          • Sant P Chawla, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Hospital
        • Principal Investigator:
          • Christopher Lieu, MD
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University - Winship Cancer Institute
        • Principal Investigator:
          • Olatunji Alese, MD
        • Contact:
          • Suzanne Scott
          • Phone Number: 404-778-4083
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Active, not recruiting
        • The University of Chicago
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Not yet recruiting
        • Center for Cancer Research at NCI
        • Contact:
          • J Glod
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Principal Investigator:
          • Rashmi Chugh, MD
        • Contact:
      • Grand Rapids, Michigan, United States, 49546
        • Active, not recruiting
        • START Midwest Michigan, PC
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Emily Slotkin, MD
        • Contact:
          • Care Advisors
          • Phone Number: 833-675-5437
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Principal Investigator:
          • Dale Shepard, MD
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University
        • Principal Investigator:
          • Michael Heinrich, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19106
        • Recruiting
        • University of Pennsylvania Abramson Cancer Center
        • Contact:
        • Principal Investigator:
          • Lee Hartner, MD
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Not yet recruiting
        • Vanderbilt University School of Medicine
        • Principal Investigator:
          • Elizabeth Davis, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • UT MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • David Hong, MD
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Active, not recruiting
        • Next Oncology
    • Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation
INBRX-109 will be escalated (3+3 design) in subjects with locally advanced or metastatic solid tumors including sarcomas.
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Experimental: Expansion Malignant Pleural Mesothelioma
Subjects with malignant pleural mesothelioma will be treated with single-agent INBRX-109 at either the MTD or RP2D.
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Experimental: Expansion Gastric Adenocarcinoma
Subjects with gastric adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Experimental: Expansion Colorectal Adenocarcinoma
Subjects with colorectal (CRC) adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Experimental: Expansion Sarcomas
Subjects with certain sarcoma subtypes will be treated with single-agent INBRX-109 at either the MTD or RP2D.
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Experimental: Combination Expansion Malignant Pleural Mesothelioma
Subjects with malignant pleural mesothelioma will be treated with INBRX-109 in combination with chemotherapies (carboplatin, cisplatin, carboplatin and pemetrexed, or cisplatin and pemetrexed)
Drug: Pemetrexed
Chemotherapy
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Drug: Carboplatin
Chemotherapy
Drug: Cisplatin
Chemotherapy
Experimental: Combination Expansion Pancreatic Adenocarcinoma
Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy
Drug: Irinotecan
Chemotherapy
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Drug: 5-fluorouracil
Chemotherapy
Experimental: Combination Expansion Ewing Sarcoma
Subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide
Drug: Irinotecan
Chemotherapy
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Drug: Temozolomide
Chemotherapy
Experimental: Combination Expansion Colorectal Adenocarcinoma
Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy
Drug: Irinotecan
Chemotherapy
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Drug: 5-fluorouracil
Chemotherapy
Experimental: Expansion Solid Tumors
Subjects with Solid tumors and high BMI will be treated with single-agent INBRX-109 at either the MTD or RP2D.
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Experimental: Combination Expansion SDH-deficient solid tumors or GIST
Subjects with SDH-deficient solid tumors or GIST will be treated with INBRX-109 in combination with temozolomide
Drug: INBRX-109
Tetravalent DR5 Agonist Antibody
Drug: Temozolomide
Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency and severity of adverse events of INBRX-109
Time Frame: Up to 2 years
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
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-109
Time Frame: Up to 2 years
The MTD and/or RP2D of INBRX-109 will be determined.
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the serum concentration time curve (AUC) of INBRX-109
Time Frame: Up to 2 years
Area under the serum concentration time curve (AUC) of INBRX-109 will be determined.
Up to 2 years
Immunogenicity of INBRX-109
Time Frame: Up to 2 years
Frequency of ant-drug antibodies (ADA) against INBRX-109 will be determined.
Up to 2 years
Maximum observed serum concentration (Cmax) of INBRX-109
Time Frame: Up to 2 years
Maximum observed serum concentration (Cmax) of INBRX-109 will be determined.
Up to 2 years
Trough observed serum concentration (Ctrough) of INBRX-109
Time Frame: Up to 2 years
Trough observed serum concentration (Cmax) of INBRX-109 will be determined.
Up to 2 years
Time to Cmax (Tmax) of INBRX-109
Time Frame: Up to 2 years
Time to Cmax (Tmax) of INBRX-109 will be determined.
Up to 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti-tumor activity of INBRX-109
Time Frame: Up to 2 years
Tumor response will be determined by RECISTv1.1.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inhibrx, Inc.

Investigators

  • Study Director: Clinical Lead, Inhibrx, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2018

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

October 11, 2018

First Submitted That Met QC Criteria

October 19, 2018

First Posted (Actual)

October 23, 2018

Study Record Updates

Last Update Posted (Estimated)

April 25, 2024

Last Update Submitted That Met QC Criteria

April 24, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ph1 INBRX-109

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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