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

NCT03715933 | Recruiting Phase 1 FDA Drug

• 1 other identifier: Ph1 INBRX-109
• Study Type: interventional
• Target: 321
• Locations: 6 countries
• Sites: 35

Brief 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).

Conditions

Ewing Sarcoma

Keywords

Phase 1; Phase 1 Clinical Trial; Solid Tumors; Sarcoma; DR5; Ewing Sarcoma

Outcome Measures

Primary Outcomes (2)

• 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 8 years

• Evaluating Tumor Response for colorectal cancers and Ewing sarcoma

  Evaluating how the tumor responds to treatment by measuring the number of patients with colorectal cancer and Ewing sarcoma that experience tumor shrinkage and for how long.

  Up to 8 years

Secondary Outcomes (3)

• Immunogenicity of INBRX-109

  Up to 8 years

• Characterize the pharmacokinetics of INBRX-109 as a single agent, and of INBRX-109 in combination with distinct chemotherapies.

  Up to 8 years

• Median progression-free survival for colorectal adenocarcinoma and Ewing sarcoma.

  Up to 8 years

Other Outcomes (2)

• Anti-tumor activity of INBRX-109

  Up to 8 years

• Potential predictive response biomarkers

  Up to 8 years

Study Arms (11)

Dose Escalation (Complete)

EXPERIMENTAL

INBRX-109 will be escalated (3+3 design) in subjects with locally advanced or metastatic solid tumors including sarcomas.

Drug: INBRX-109

Expansion Malignant Pleural Mesothelioma (Complete)

EXPERIMENTAL

Subjects with malignant pleural mesothelioma will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Drug: INBRX-109

Expansion Gastric Adenocarcinoma (Complete)

EXPERIMENTAL

Subjects with gastric adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Drug: INBRX-109

Expansion Colorectal Adenocarcinoma (Complete)

EXPERIMENTAL

Subjects with colorectal (CRC) adenocarcinoma will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Drug: INBRX-109

Expansion Sarcomas (Complete)

EXPERIMENTAL

Subjects with certain sarcoma subtypes will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Drug: INBRX-109

Combination Expansion Malignant Pleural Mesothelioma (Complete)

EXPERIMENTAL

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: INBRX-109; Drug: carboplatin; Drug: pemetrexed

Combination Expansion Pancreatic Adenocarcinoma (Complete)

EXPERIMENTAL

Subjects with pancreatic adenocarcinoma will be treated with INBRX-109 in combination with 5FU/irinotecan based chemotherapy

Drug: INBRX-109; Drug: Irinotecan; Drug: Leucovorin; Drug: Fluorouracil

Combination Expansion Ewing Sarcoma

EXPERIMENTAL

Subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide

Drug: INBRX-109; Drug: Irinotecan; Drug: Temozolomide

Combination Expansion Colorectal Adenocarcinoma (Complete)

EXPERIMENTAL

Subjects with colorectal adenocarcinoma will be treated with INBRX-109 in combination with FOLFIRI based chemotherapy

Drug: INBRX-109; Drug: Irinotecan; Drug: Leucovorin; Drug: Fluorouracil

Expansion Solid Tumors (Complete)

EXPERIMENTAL

Subjects with Solid tumors and high BMI will be treated with single-agent INBRX-109 at either the MTD or RP2D.

Drug: INBRX-109

Combination Expansion SDH-deficient solid tumors or GIST (Complete)

EXPERIMENTAL

Subjects with SDH-deficient solid tumors or GIST will be treated with INBRX-109 in combination with temozolomide

Drug: INBRX-109; Drug: Temozolomide

Interventions

INBRX-109 DRUG

Tetravalent DR5 Agonist Antibody

Combination Expansion Colorectal Adenocarcinoma (Complete); Combination Expansion Ewing Sarcoma; Combination Expansion Malignant Pleural Mesothelioma (Complete); Combination Expansion Pancreatic Adenocarcinoma (Complete); Combination Expansion SDH-deficient solid tumors or GIST (Complete); Dose Escalation (Complete); Expansion Colorectal Adenocarcinoma (Complete); Expansion Gastric Adenocarcinoma (Complete); Expansion Malignant Pleural Mesothelioma (Complete); Expansion Sarcomas (Complete); Expansion Solid Tumors (Complete)

Irinotecan DRUG

Chemotherapy

Combination Expansion Colorectal Adenocarcinoma (Complete); Combination Expansion Ewing Sarcoma; Combination Expansion Pancreatic Adenocarcinoma (Complete)

Temozolomide DRUG

Chemotherapy

Combination Expansion Ewing Sarcoma; Combination Expansion SDH-deficient solid tumors or GIST (Complete)

carboplatin DRUG

chemotherapy

Combination Expansion Malignant Pleural Mesothelioma (Complete)

pemetrexed DRUG

chemotherapy

Combination Expansion Malignant Pleural Mesothelioma (Complete)

Leucovorin DRUG

chemotherapy

Combination Expansion Colorectal Adenocarcinoma (Complete); Combination Expansion Pancreatic Adenocarcinoma (Complete)

Fluorouracil DRUG

chemotherapy

Combination Expansion Colorectal Adenocarcinoma (Complete); Combination Expansion Pancreatic Adenocarcinoma (Complete)

Eligibility Criteria

• Age: 12 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 with locally advanced or metastatic, unresectable disease, who have received at least 2 but no more than 3 prior lines of systemic therapy.
• 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) 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).
• Estimated life expectancy of at least 12 weeks.
• Availability of archival tissue or fresh cancer biopsy are mandatory.

You may not qualify if:

• 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.
• Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
• 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. Exceptions per protocol.
• Prior or concurrent malignancies. Exceptions per protocol.
• Hematologic malignancies.
• 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.
• 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.
• Known sensitivity or contraindications to the following drugs:
• Ewing sarcoma: irinotecan or TMZ
• colorectal adenocarcinoma: FU, leucovorin, or irinotecan
• Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease less than 3 months prior to enrollment.
• 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.

Sponsors & Collaborators

• Inhibrx Biosciences, Inc: lead

Study Sites (35)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

COMPLETED

Precision NextGen Oncology and Research

Beverly Hills, California, 90212, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

University of California, San Diego (UCSD) - Moores Cancer Center

San Diego, California, 92093, United States

RECRUITING

University of California, San Francisco (UCSF)

San Francisco, California, 94110, United States

RECRUITING

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

RECRUITING

University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

Emory University - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

The University of Chicago

Chicago, Illinois, 60637, United States

COMPLETED

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

START Midwest Michigan, PC

Grand Rapids, Michigan, 49546, United States

RECRUITING

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Children's Hospital of Philadelphia- Center for Childhood Cancer Research

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19106, United States

RECRUITING

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232, United States

RECRUITING

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

COMPLETED

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

NEXT Oncology - Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

La Fondazione e l'Istituto di Candiolo

Candiolo, 10060, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20123, Italy

RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Academisch Ziekenhuis Leiden

Leiden, Netherlands

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

RECRUITING

Hospital Clinico San Carlos

Madrid, 28040, Spain

RECRUITING

Great North Children's Hospital

London, EC4V 3BJ, United Kingdom

RECRUITING

University College London Hospital

London, NW1 2PG, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

RECRUITING

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

RECRUITING

Related Publications (1)

• Subbiah V, Chawla SP, Conley AP, Wilky BA, Tolcher A, Lakhani NJ, Berz D, Andrianov V, Crago W, Holcomb M, Hussain A, Veldstra C, Kalabus J, O'Neill B, Senne L, Rowell E, Heidt AB, Willis KM, Eckelman BP. Preclinical Characterization and Phase I Trial Results of INBRX-109, A Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma. Clin Cancer Res. 2023 Aug 15;29(16):2988-3003. doi: 10.1158/1078-0432.CCR-23-0974.

  PMID: 37265425 DERIVED

MeSH Terms

Conditions

Sarcoma, Ewing; Sarcoma

Interventions

Irinotecan; Temozolomide; Carboplatin; Pemetrexed; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines

Study Officials

• Clinical Lead

  Inhibrx Biosciences, Inc

  STUDY DIRECTOR

Central Study Contacts

Study Director, -Inhibrx

CONTACT

858-500-7833; clinicaltrials@inhibrx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: October 23, 2018
• Study Start: October 8, 2018
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (22); FR (2); GB (4); NL (2); ES (3); IT (2)