Ewing SarcomaPhase 1NCT03715933
Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas
A Phase 1 study testing INBRX-109, Irinotecan and Temozolomide in people with Ewing Sarcoma and Colorectal Adenocarcinoma, run by Inhibrx Biosciences, Inc at 37 sites in 6 countries.
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). Read more about this study
- Who is it for?
- Ages 12 to 85 years
- Conditions the study is for
- Ewing Sarcoma, Colorectal Adenocarcinoma
- What is being tested?
- INBRX-109, Irinotecan and Temozolomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 411 participants
- Where
- 37 sitesin 6 countries
- Study dates
- 8 Oct 2018to Jun 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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 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.
- Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma) criteria.
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- 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.
Who cannot join
- 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.
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- 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.
- 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.
- 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, irinotecan, bevacizumab or FTP/TPI
- 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.
- 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.
- Other exclusion criteria per protocol.
Trial locations and contacts
37 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
37 sites in 6 countries
United States24 sites, 19 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Myron Hepner, mhepner@med.umich.edu
Rashmi Chugh, MD
- Recruiting
Emory University - Winship Cancer Institute
Atlanta, Georgia, 30322
Kimberly Homere, 404-778-6583, kimberly.homere@emory.edu
Olatunji Alese, MD
- Recruiting
University of Colorado Hospital
Aurora, Colorado, 80045
Michaela Riley, michaela.riley@cuanschutz.edu
Christopher Lieu, MD
- Recruiting
Precision NextGen Oncology and Research
Beverly Hills, California, 90212
Rebecca Godin, MSN, FNP, 424-777-0708, rebeccag@nextgenonc.com
Ravleen Kaur, BS, (424) 777-0708, RavKaur@nextgenonc.com
- Recruiting
University of Virginia
Charlottesville, Virginia, 22903
Sarah Sommer, 434-924-7613, ss2vz@uvahealth.org
Ludimila Cavalcante, MD
- Completed
The University of Chicago
Chicago, Illinois, 60637
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Michael D Deel, MD, 513-636-3200, michael.deel@cchmc.org
Lori Backus, BA, 513-636-2047, Lori.backus@cchmc.org
- Completed
Cleveland Clinic
Cleveland, Ohio, 44195
- Recruiting
City of Hope
Duarte, California, 91010
Heather Lewis, 626-256-4673, healewis@coh.org
New Patient Services Coordinator, 1-800-826-4673, newpatientref@coh.org
- Recruiting
NEXT Oncology - Virginia
Fairfax, Virginia, 22031
Anthony Young, 703-783-4536, ayoung@nextoncology.com
NXTVIR_Coordinators@nextoncology.com
- Recruiting
START Midwest Michigan, PC
Grand Rapids, Michigan, 49546
Julie Burns, 616-954-5559, julie.burns@startmidwest.com
Leland Rouse, leland.rouse@startmidwest.com
- Recruiting
UT MD Anderson Cancer Center
Houston, Texas, 77030
Emily Scott, (713) 745-2243, EMScott1@mdanderson.org
David Hong, MD
- Recruiting
Valkyrie Clinical Trials
Los Angeles, California, 90067
Carla Collier, carla.collier@valkyrieclinicaltrials.com
David Berz, MD
- Recruiting
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232
Samrah Ahmed, 615.936.9598, samrah.ahmed@vumc.org
Elizabeth Davis, MD
- Recruiting
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Care Advisors, 833-675-5437
Emily Slotkin, MD
- Recruiting
Children's Hospital of Orange County-Rady Children's Health
Orange, California, 92868
Dorian Chan Clinical Research Nurse Coordinator, RN, BSN, 714-509-7868, dchan@choc.org
Claudia Mousa, RN, 714-509-7868, Claudia.Mousa@choc.org
- Recruiting
Children's Hospital of Philadelphia- Center for Childhood Cancer Research
Philadelphia, Pennsylvania, 19104
Matthew Stein, 267-425-3169, steinm3@chop.edu
precisionmedicinetrialscoordinators@chop.edu
- Recruiting
University of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, 19106
Sarcoma Research, SarcomaResearch@uphs.upenn.edu
Lee Hartner, MD
- Recruiting
Oregon Health & Science University
Portland, Oregon, 97239
Zach Nelson, 503-494-0833, nelsonz@ohsu.edu
Michael Heinrich, MD
- Completed
NEXT Oncology
San Antonio, Texas, 78229
- Withdrawn
University of California, San Diego (UCSD) - Moores Cancer Center
San Diego, California, 92093
- Recruiting
University of California, San Francisco (UCSF)
San Francisco, California, 94110
Lisa Tan, 415-866-7866, lisa.tan@ucsf.edu
Varun Monga, MD
- Recruiting
Sarcoma Oncology Center
Santa Monica, California, 90403
Victoria Chua-Alcala, 310-552-9999, vchua@sarcomaoncology.com
Sant P Chawla, MD
- Completed
HonorHealth Research Institute
Scottsdale, Arizona, 85258
United Kingdom4 sites, 4 recruiting
- Recruiting
Great North Children's Hospital
London, EC4V 3BJ
Quentin Campbell-Hewson, MD
- Recruiting
University College London Hospital
London, NW1 2PG
Sandra Strauss, MD
- Recruiting
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
Andrea Napolitano, MD
- Recruiting
Royal Manchester Children's Hospital
Manchester, M13 9WL
Bernadette Maria Dymphna Brennan
Spain3 sites, 3 recruiting
- Recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Elena Elez, MD
- Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Ana Sebio Garcia, MD
- Recruiting
Hospital Clinico San Carlos
Madrid, 28040
Antonio Casado Herraez
France2 sites, 2 recruiting
- Recruiting
Centre Leon Berard
Lyon, 69008
Mehdi Brahmi, MD
- Recruiting
Gustave Roussy
Villejuif, 94805
Pablo Berlanga, MD
Italy2 sites, 2 recruiting
- Recruiting
La Fondazione e l'Istituto di Candiolo
Candiolo, 10060
Sandra Aliberti, MD
- Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20123
Salvatore Provenzano, MD
Roberto Luksch, MD
Netherlands2 sites, 2 recruiting
- Recruiting
University Medical Center Groningen
Groningen
Jacco de Haan, MD
- Recruiting
Academisch Ziekenhuis Leiden
Leiden
André (Hans) Gelderblom, MD
About this study
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
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, Colorectal Adenocarcinoma
- Being tested
- INBRX-109, Irinotecan, Temozolomide, carboplatin, pemetrexed
- Keywords
- Phase 1, Phase 1 Clinical Trial, Solid Tumors, Sarcoma, DR5, Ewing Sarcoma, CRC, colorectal adenocarcinoma
- Medical subject headings
- Sarcoma, Ewing, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INBRX-109Drug
Tetravalent DR5 Agonist Antibody
IrinotecanDrug
Chemotherapy
TemozolomideDrug
Chemotherapy
carboplatinDrug
chemotherapy
pemetrexedDrug
chemotherapy
LeucovorinDrug
chemotherapy
FluorouracilDrug
chemotherapy
BevacizumabDrug
targeted therapy
Trifluridine + TipiracilDrug
chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (Complete) | Experimental | INBRX-109 will be escalated (3+3 design) in subjects with locally advanced or metastatic solid tumors including sarcomas. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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) Receives: 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 Receives: Drug: INBRX-109; Drug: Irinotecan; Drug: Leucovorin; Drug: Fluorouracil |
| Combination Expansion Adult Ewing Sarcoma | Experimental | Adult subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide Receives: 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 Receives: 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. Receives: 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 Receives: Drug: INBRX-109; Drug: Temozolomide |
| Combination Expansion Colorectal Adenocarcinoma patients with FOLFIRI plus bevacizumab | Experimental | Colorectal adenocarcinoma will be treated with INBRX-109 with FOLFIRI (FU, leucovorin, and irinotecan) plus bevacizumab Receives: Drug: INBRX-109; Drug: Irinotecan; Drug: Leucovorin; Drug: Fluorouracil; Drug: Bevacizumab |
| Combination Expansion Colorectal Adenocarcinoma with FTD/TPI plus bevacizumab | Experimental | Colorectal adenocarcinoma will be treated with INBRX-109 with FTD/TPI plus bevacizumab Receives: Drug: INBRX-109; Drug: Bevacizumab; Drug: Trifluridine + Tipiracil |
| Combination Expansion Adolescent Ewing Sarcoma | Experimental | Adolescent (12 to <18) subjects with Ewing Sarcoma will be treated with INBRX-109 in combination with irinotecan and temozolomide Receives: Drug: INBRX-109; Drug: Irinotecan; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 8 years
Secondary outcomes (3)
Immunogenicity of INBRX-109
Frequency of ant-drug antibodies (ADA) against INBRX-109 will be determined.
Measured: Up to 8 years
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.
Measured: Up to 8 years
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.
Measured: Up to 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2018
- Study start8 Oct 2018
- Primary completionDec 2028 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ewing SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 411 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Inhibrx Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Lead, Study director, Inhibrx Biosciences, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03715933
- Sponsor's protocol ID
- Ph1 INBRX-109
- Status last verified
- May 2026
- First submitted
- 11 Oct 2018
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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