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Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

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ClinicalTrials.gov Identifier: NCT04198766
Recruitment Status : Recruiting
First Posted : December 13, 2019
Last Update Posted : July 20, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Inhibrx, Inc.

Brief Summary:
This is a first-in-human, open-label, non-randomized, 4-part Phase 1 trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda).

Condition or disease Intervention/treatment Phase
Solid Tumor Non-Small Cell Lung Cancer Melanoma Head and Neck Cancer Gastric Cancer Renal Cell Carcinoma Urothelial Carcinoma Drug: INBRX-106 - Hexavalent OX40 agonist antibody Drug: Pembrolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors
Actual Study Start Date : December 10, 2019
Estimated Primary Completion Date : December 2, 2022
Estimated Study Completion Date : March 15, 2023


Arm Intervention/treatment
Experimental: Part 1 INBRX-106 Escalation
INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors.
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).

Experimental: Part 2 INBRX-106 Expansion
Subjects with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-106 at the RP2D.
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).

Experimental: Part 3 INBRX-106 Escalation in Combination with Pembrolizumab
INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors.
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).

Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Name: Keytruda

Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab
Subjects with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-106 at the RP2D in combination with pembrolizumab.
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).

Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Name: Keytruda




Primary Outcome Measures :
  1. Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
    Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0

  2. Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
    Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0

  3. MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
    Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-106 and INBRX-106 in combination with pembrolizumab


Secondary Outcome Measures :
  1. Area under the serum concentration time curve (AUC) of INBRX-106 [ Time Frame: 2-4 years ]
    Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

  2. Maximum observed serum concentration (Cmax) of INBRX-106 [ Time Frame: 2-4 years ]
    Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

  3. Trough observed serum concentration (Ctrough) of INBRX-106 [ Time Frame: 2-4 years ]
    Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

  4. Time to Cmax (Tmax) of INBRX-106 [ Time Frame: 2-4 years ]
    Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

  5. Immunogenicity of INBRX-106 [ Time Frame: 2-4 years ]
    Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab will be determined.


Other Outcome Measures:
  1. Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
    Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).

  2. Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
    Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Select Inclusion Criteria:

  • Males or females aged ≥18 years.
  • Parts 1 and 3 (escalation cohorts): Subjects with locally advanced or metastatic non resectable solid tumors, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.
  • Part 2 (single-agent expansion cohort): Subjects with NSCLC, melanoma, HNSCC, G/GEA, RCC, or TCC, with locally advanced or metastatic, non-resectable disease, which has progressed despite all standard therapies or for whom no standard or clinically acceptable therapy exists.
  • Part 4 (expansion cohorts in combination with pembrolizumab): Subjects with melanoma, HNSCC, G/GEA, RCC, or TCC, or NSCLC, with locally advanced or metastatic, non resectable disease, which has progressed despite all standard therapies or for whom no standard or clinically acceptable therapy exists.
  • All subjects with non-squamous NSCLC must have documentation of absence of tumor activating EGFR mutations and absence of ALK gene rearrangements.
  • PD-L1 by IHC (22C3): Parts 1 and 3: IHC optional. Part 2: IHC result mandatory but any score allowed. Part 4: Combined Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥1% for NSCLC).
  • Adequate hematologic, coagulation, hepatic and renal function and ECOG score as defined per protocol.

Select Exclusion Criteria:

  • Prior exposure to OX40 agonists.
  • Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug with certain exceptions.
  • Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's lymphoma and multiple myeloma)
  • 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-106.
  • Known or active primary central nervous system (CNS) tumors, leptomeningeal disease and CNS metastases. Exception: Subjects with previously treated, asymptomatic, and clinically stable CNS metastases may be allowed study entry if certain criteria apply.
  • Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply.
  • Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply.
  • Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. Certain exceptions as defined in protocol apply.
  • History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection for Parts 1 and 3. Exceptions as defined in protocol for expansion cohorts will apply.
  • Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications.
  • Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months; left ventricular ejection fraction (LVEF) < 50%; New York Heart Association (NYHA) Class III or IV congestive heart failure; or uncontrolled hypertension.
  • Active, hemodynamically significant pulmonary embolism within 3 months prior to enrollment on this trial.
  • Major surgery within 4 weeks prior to enrollment on this trial.
  • Anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to the first dose of study drug.
  • Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation.
  • Additional in- and exclusion criteria per protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04198766


Contacts
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Contact: Terri Boyea, Director Clin Ops 858-500-7833 terri@inhibrx.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: New Patient Services    800-826-4673    sthiagarajan@coh.org   
United States, Georgia
Winship Cancer Institute - Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Suzanne Scott    404-778-4083    suzanne.e.scott@emrory.edu   
United States, Illinois
The University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Jeffery Chin    773-834-5004    jchin18@medicine.bsd.uchicago.edu   
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Jordan Harrelson    319-467-5831    Jordan-harrelson@uiowa.edu   
United States, Michigan
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49546
Contact: Katie Robinson    616-389-1739    Katie.Robinson@startmidwest.com   
United States, Nebraska
Nebraska Cancer Specialists Recruiting
Omaha, Nebraska, United States, 68130
Contact: Gladys Pierce    402-691-6972    gpierce@nebraskacancer.com   
United States, Oregon
Providence Cancer Institute Recruiting
Portland, Oregon, United States, 97213
Contact: Tara Foote    503-215-7192    ORCanClinRsrch@providence.org   
United States, Texas
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Kayla Dotson    210-595-5670    kdotson@nextoncology.com   
Sponsors and Collaborators
Inhibrx, Inc.
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Klaus Wagner, MD, PhD Inhibrx, Inc.
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Responsible Party: Inhibrx, Inc.
ClinicalTrials.gov Identifier: NCT04198766    
Other Study ID Numbers: Ph 1 INBRX-106
MK3475 KEYNOTE A99 ( Other Identifier: Merck & Co., Inc. )
First Posted: December 13, 2019    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Inhibrx, Inc.:
Solid Tumors
Head and Neck Cancer
Stomach Cancer
Gastric Cancer
Lung Cancer
Non-Small Cell Lung Cancer
Kidney Cancer
Bladder Cancer
Phase 1
Phase 1 Clinical Trial
Melanoma
Renal Cell Carcinoma
Urothelial Carcinoma
OX40
PD-1
Pembrolizumab
Keytruda
Additional relevant MeSH terms:
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Lung Neoplasms
Stomach Neoplasms
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Gastrointestinal Neoplasms
Digestive System Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Melanoma
Carcinoma, Renal Cell
Carcinoma, Transitional Cell
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Nevi and Melanomas
Digestive System Diseases
Gastrointestinal Diseases