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RecruitingNCT03715933Updated Sep 8, 2026

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

A Phase 1 interventional study of INBRX-109 and Irinotecan in Ewing Sarcoma and Colorectal Adenocarcinoma, sponsored by Inhibrx Biosciences, Inc. Recruiting at 37 sites in 6 countries. Open to participants aged 12 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-09-08.

Sponsored by Inhibrx Biosciences, Inc · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
411
Allocation
Non-randomized
Ages
12 Years to 85 Years
Sex
All
01

Study 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).

02

Conditions studied

  • Ewing Sarcoma
  • Colorectal Adenocarcinoma

Keywords

  • Phase 1
  • Phase 1 Clinical Trial
  • Solid Tumors
  • Sarcoma
  • DR5
  • Ewing Sarcoma
  • CRC
  • colorectal adenocarcinoma
03

Who can participate

Ages eligible
12 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
411 participants (estimated)

Study arms

  • Experimental
    Dose Escalation (Complete)

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

    Drug: INBRX-109

  • Experimental
    Expansion Malignant Pleural Mesothelioma (Complete)

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

    Drug: INBRX-109

  • Experimental
    Expansion Gastric Adenocarcinoma (Complete)

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

    Drug: INBRX-109

  • Experimental
    Expansion Colorectal Adenocarcinoma (Complete)

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

    Drug: INBRX-109

  • Experimental
    Expansion Sarcomas (Complete)

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

    Drug: INBRX-109

  • Experimental
    Combination Expansion Malignant Pleural Mesothelioma (Complete)

    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

  • Experimental
    Combination Expansion Pancreatic Adenocarcinoma (Complete)

    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

  • Experimental
    Combination Expansion Adult Ewing Sarcoma

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

    Drug: INBRX-109 · Drug: Irinotecan · Drug: Temozolomide

  • Experimental
    Combination Expansion Colorectal Adenocarcinoma (Complete)

    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

  • Experimental
    Expansion Solid Tumors (Complete)

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

    Drug: INBRX-109

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

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

    Drug: INBRX-109 · Drug: Temozolomide

  • Experimental
    Combination Expansion Colorectal Adenocarcinoma patients with FOLFIRI plus bevacizumab

    Colorectal adenocarcinoma will be treated with INBRX-109 with FOLFIRI (FU, leucovorin, and irinotecan) plus bevacizumab

    Drug: INBRX-109 · Drug: Irinotecan · Drug: Leucovorin · Drug: Fluorouracil · Drug: Bevacizumab

  • Experimental
    Combination Expansion Colorectal Adenocarcinoma with FTD/TPI plus bevacizumab

    Colorectal adenocarcinoma will be treated with INBRX-109 with FTD/TPI plus bevacizumab

    Drug: INBRX-109 · Drug: Bevacizumab · Drug: Trifluridine + Tipiracil

  • Experimental
    Combination Expansion Adolescent Ewing Sarcoma

    Adolescent (12 to \<18) subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide

    Drug: INBRX-109 · Drug: Irinotecan · Drug: Temozolomide

Interventions

  • DrugINBRX-109

    Tetravalent DR5 Agonist Antibody

  • DrugIrinotecan

    Chemotherapy

  • DrugTemozolomide

    Chemotherapy

  • Drugcarboplatin

    chemotherapy

  • Drugpemetrexed

    chemotherapy

  • DrugLeucovorin

    chemotherapy

  • DrugFluorouracil

    chemotherapy

  • DrugBevacizumab

    targeted therapy

  • DrugTrifluridine + Tipiracil

    chemotherapy

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Up to 8 years

  2. 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.

    Time frame: Up to 8 years

Secondary outcomes

  1. Immunogenicity of INBRX-109

    Frequency of ant-drug antibodies (ADA) against INBRX-109 will be determined.

    Time frame: Up to 8 years

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

    A measurement which indicates how the body processes INBRX-109 and how long it stays in the system.

    Time frame: Up to 8 years

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

    Progression-free survival is defined as the time from start of study treatment until documented disease progression or death.

    Time frame: Up to 8 years

Other outcomes

  1. Anti-tumor activity of INBRX-109

    Tumor response will be determined by RECISTv1.1.

    Time frame: Up to 8 years

  2. Potential predictive response biomarkers

    Evaluate the relationship between potential predictive response biomarkers and efficacy of INBRX-109

    Time frame: Up to 8 years

06

Study locations

32 of 37 sites recruiting
  • 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
    • Heather Lewis · Contact · healewis@coh.org · 626-256-4673
    • New Patient Services Coordinator · Contact · newpatientref@coh.org · 1-800-826-4673
    • Marwan Fakih, MD · Principal investigator
    Recruiting
  • Valkyrie Clinical Trials
    Los Angeles, California 90067, United States
    Recruiting
  • Children's Hospital of Orange County-Rady Children's Health
    Orange, California 92868, United States
    • Dorian Chan Clinical Research Nurse Coordinator, RN, BSN · Contact · dchan@choc.org · 714-509-7868
    • Claudia Mousa, RN · Contact · Claudia.Mousa@choc.org · 714-509-7868
    • Dr. Elyssa Rubin, MD · Principal investigator
    Recruiting
  • University of California, San Diego (UCSD) - Moores Cancer Center
    San Diego, California 92093, United States
    Withdrawn
  • University of California, San Francisco (UCSF)
    San Francisco, California 94110, United States
    • Lisa Tan · Contact · lisa.tan@ucsf.edu · 415-866-7866
    • Varun Monga, MD · Principal investigator
    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
    • Care Advisors · Contact · 833-675-5437
    • Emily Slotkin, MD · Principal investigator
    Recruiting
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229, United States
    Recruiting
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
    Completed
  • Oregon Health & Science University
    Portland, Oregon 97239, United States
    • Zach Nelson · Contact · nelsonz@ohsu.edu · 503-494-0833
    • Michael Heinrich, MD · Principal investigator
    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
    • Samrah Ahmed · Contact · samrah.ahmed@vumc.org · 615.936.9598
    • Elizabeth Davis, MD · Principal investigator
    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
    • Sarah Sommer · Contact · ss2vz@uvahealth.org · 434-924-7613
    • Ludimila Cavalcante, MD · Principal investigator
    Recruiting
  • NEXT Oncology - Virginia
    Fairfax, Virginia 22031, United States
    Recruiting
  • Centre Leon Berard
    Lyon, 69008, France
    • Mehdi Brahmi, MD · Principal investigator
    Recruiting
  • Gustave Roussy
    Villejuif, 94805, France
    • Pablo Berlanga, MD · Principal investigator
    Recruiting
  • La Fondazione e l'Istituto di Candiolo
    Candiolo, 10060, Italy
    • Sandra Aliberti, MD · Principal investigator
    Recruiting
  • Fondazione IRCCS Istituto Nazionale dei Tumori
    Milan, 20123, Italy
    • Salvatore Provenzano, MD · Principal investigator
    • Roberto Luksch, MD · Principal investigator
    Recruiting
  • University Medical Center Groningen
    Groningen, Netherlands
    • Jacco de Haan, MD · Principal investigator
    Recruiting
  • Academisch Ziekenhuis Leiden
    Leiden, Netherlands
    • André (Hans) Gelderblom, MD · Principal investigator
    Recruiting
  • Hospital Universitario Vall d'Hebron
    Barcelona, 08035, Spain
    • Elena Elez, MD · Principal investigator
    Recruiting
  • Hospital de la Santa Creu i Sant Pau
    Barcelona, 08041, Spain
    • Ana Sebio Garcia, MD · Principal investigator
    Recruiting
  • Hospital Clinico San Carlos
    Madrid, 28040, Spain
    • Antonio Casado Herraez · Principal investigator
    Recruiting
  • Great North Children's Hospital
    London, EC4V 3BJ, United Kingdom
    • Quentin Campbell-Hewson, MD · Principal investigator
    Recruiting
  • University College London Hospital
    London, NW1 2PG, United Kingdom
    • Sandra Strauss, MD · Principal investigator
    Recruiting
  • The Royal Marsden NHS Foundation Trust
    London, SW3 6JJ, United Kingdom
    • Andrea Napolitano, MD · Principal investigator
    Recruiting
  • Royal Manchester Children's Hospital
    Manchester, M13 9WL, United Kingdom
    • Bernadette Maria Dymphna Brennan · Principal investigator
    Recruiting
07

References and documents

Publications

  • 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. PubMed 37265425 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03715933
Lead sponsor
Inhibrx Biosciences, Inc
Responsible party
Sponsor
First posted
Oct 23, 2018
Start date
Oct 8, 2018
Primary completion
Dec 2028 (estimated)
Completion
Jun 2029 (estimated)
Last update
Sep 8, 2026

Study contacts

Study Director, -Inhibrx
Contact
clinicaltrials@inhibrx.com
858-500-7833
Clinical Lead
study director · Inhibrx Biosciences, Inc

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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