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Study of INBRX-105 in Patients With Solid Tumors, Hodgkin or Non-Hodgkin Lymphoma (PDL1x41BB)

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ClinicalTrials.gov Identifier: NCT03809624
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : February 5, 2019
Sponsor:
Information provided by (Responsible Party):
Inhibrx, Inc.

Brief Summary:
This is a first-in-human, open-label, nonrandomized, two-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-105. INBRX-105, a next generation bispecific antibody, targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. INBRX-105 provides immune checkpoint blockade of PD-L1 as well as conditional T cell co-stimulation through 4-1BB agonism for localized immune stimulation.

Condition or disease Intervention/treatment Phase
Metastatic Solid Tumors Hodgkin Lymphoma Non Hodgkin Lymphoma Non-small Cell Lung Cancer Melanoma Head and Neck Squamous Cell Carcinoma Gastric Adenocarcinoma Renal Cell Carcinoma Urothelial Carcinoma Esophageal Adenocarcinoma Drug: INBRX-105 - PDL1x41BB antibody Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 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-105 in Patients With Locally Advanced or Metastatic Solid Tumors, Hodgkin or Non-Hodgkin Lymphoma
Actual Study Start Date : January 30, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: Part 1 Escalation
INBRX-105 will be escalated in subjects with locally advanced or metastatic solid tumors, Hodgkin or Non-Hodgkin lymphoma.
Drug: INBRX-105 - PDL1x41BB antibody
The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.

Experimental: Expansion Cohort Non-small Cell Lung Cancer
Subjects will be treated with single-agent INBRX-105 at either the MTD or RP2D.
Drug: INBRX-105 - PDL1x41BB antibody
The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.

Experimental: Expansion Cohort Melanoma
Subjects will be treated with single-agent INBRX-105 at either the MTD or RP2D.
Drug: INBRX-105 - PDL1x41BB antibody
The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.

Experimental: Expansion Cohort PD-L1 Basket
Subjects with head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with single-agent INBRX-105 at either the MTD or RP2D.
Drug: INBRX-105 - PDL1x41BB antibody
The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.




Primary Outcome Measures :
  1. Frequency of adverse events of INBRX-105 [ Time Frame: Up to 2-3 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-105 [ Time Frame: Up to 2-3 years ]
    Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

  3. Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    The MTD and/or RP2D of INBRX-105 will be determined.


Secondary Outcome Measures :
  1. Area under the serum concentration time curve (AUC) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Area under the serum concentration time curve (AUC) of INBRX-105 will be determined.

  2. Maximum observed serum concentration (Cmax) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Maximum observed serum concentration (Cmax) of INBRX-105 will be determined.

  3. Trough observed serum concentration (Ctrough) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Trough observed serum concentration (Cmax) of INBRX-105 will be determined.

  4. Time to Cmax (Tmax) of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Time to Cmax (Tmax) of INBRX-105 will be determined.

  5. Immunogenicity of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Frequency of anti-drug antibodies (ADA) against INBRX-105 will be determined.


Other Outcome Measures:
  1. Anti-tumor activity of INBRX-105 [ Time Frame: Up to 2-3 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-105 [ Time Frame: Up to 2-3 years ]
    Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).

  3. Anti-tumor activity of INBRX-105 [ Time Frame: Up to 2-3 years ]
    Tumor response will be determined by Response Evaluation Criteria in Lymphoma (RECIL 2017) if applicable.



Information from the National Library of Medicine

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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

Inclusion Criteria:

  • Part 1 (escalation): Patients with locally advanced or metastatic non-resectable solid tumors, Hodgkin or Non-Hodgkin lymphoma whose disease has progressed despite standard therapy and for whom no further standard therapy exists, or who refuse available standard treatment options.
  • Part 2 (expansion cohorts): Patients with non-small cell lung cancer, melanoma, and PD-L1 basket cohort consisting of head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, or urothelial (transitional) cell carcinoma, with locally advanced or metastatic, non-resectable disease, which has progressed despite standard therapy or for whom no standard or clinically acceptable therapy exists.
  • Refractory or relapsed to anti-PD-1 or anti-PD-L1, and anti-CTLA4 if applicable (NOTE: Only for tumor types, for which these checkpoint inhibitors are FDA approved).
  • PD-L1 positivity by immunohistochemistry (IHC). Part 1 (escalation) PD-L1 positivity is not required. Expansion cohorts: Combined Positive Score (CPS) or Tumor Proportion Score (TPS) ≥ 5%.
  • 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 Part 2.

Exclusion Criteria:

  • Prior exposure to 4-1BB 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. Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives. NOTE: Previous exposure to anti-PD-L1 checkpoint inhibitor requires a minimum washout period of 24 weeks prior to the first dose of study drug.
  • Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, and multiple myeloma) other than lymphoma.
  • 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-105.
  • 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 Part 1. Exceptions as defined in protocol for expansion cohorts will apply.
  • History of hepatitis or cirrhosis (e.g., non-alcohol steatohepatitis, alcohol or drug-related, autoimmune, hepatitis B, or hepatitis C) for Part 1. 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.

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): NCT03809624


Contacts
Contact: Kirsti Cook, SrDirClinOps 949-264-3862 clinicaltrials@inhibrx.com
Contact: Rebecca Penninga, ClinLead clinicaltrials@inhibrx.com

Locations
United States, Texas
NEXT Oncoloy Recruiting
San Antonio, Texas, United States, 78240
Contact: Sarah Gomez    210-595-5670    sgomez@nextsat.com   
Sponsors and Collaborators
Inhibrx, Inc.
Investigators
Study Director: Klaus Wagner, MD, PhD Inhibrx, Inc.

Responsible Party: Inhibrx, Inc.
ClinicalTrials.gov Identifier: NCT03809624     History of Changes
Other Study ID Numbers: Ph 1 INBRX-105
First Posted: January 18, 2019    Key Record Dates
Last Update Posted: February 5, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
Lung Cancer
Head and Neck Cancer
Stomach Cancer
Gastric Cancer
Kidney Cancer
Renal Cancer
Phase 1
Phase 1 Clinical Trial
Hodgkin Lymphoma
Non Hodgkin Lymphoma
Melanoma
Renal cell carcinoma
Urothelial Carcinoma
PDL1
41BB
PD-L1
4-1BB

Additional relevant MeSH terms:
Head and Neck Neoplasms
Esophageal Neoplasms
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Squamous Cell
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Esophageal Diseases
Lymphoma
Carcinoma
Carcinoma, Non-Small-Cell Lung
Melanoma
Carcinoma, Squamous Cell
Adenocarcinoma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Carcinoma, Renal Cell