Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors Including Head and Neck Cancer

NCT ID: NCT03809624

Last Updated: 2024-10-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-30

Study Completion Date

2024-10-03

Brief Summary

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This is a first-in-human, open-label, nonrandomized, four-part trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX-105 and INBRX-105 in combination with Pembrolizumab. 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 localized conditional T-cell co-stimulation through 4-1BB agonism.

Detailed Description

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Conditions

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Metastatic Solid Tumors Non-small Cell Lung Cancer Melanoma Head and Neck Squamous Cell Carcinoma Gastric Adenocarcinoma Renal Cell Carcinoma Esophageal Adenocarcinoma Nasopharyngeal Carcinoma Oropharyngeal Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Single Agent Escalation

INBRX-105 will be escalated in patients with locally advanced or metastatic solid tumors.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Expansion Cohort Non-small Cell Lung Cancer

Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Expansion Cohort Melanoma

Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Expansion Cohort PD-L1 Positive Basket

Patients with 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.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Expansion Cohort Nasopharyngeal or Oropharyngeal Carcinoma

Patients with head and neck squamous cell carcinoma (NPC or OPC) will be treated with single-agent INBRX-105 at either the MTD or RP2D.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

INBRX-105 Escalation in Combination with Pembrolizumab

INBRX-105 will be escalated in combination with Pembrolizumab in pateitns with locally advanced or metastatic solid tumors.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Pembrolizumab

Intervention Type DRUG

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

Combination Expansion Cohort Non-small Cell Lung Cancer

CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Pembrolizumab

Intervention Type DRUG

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

Combination Expansion Cohort Melanoma

CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Pembrolizumab

Intervention Type DRUG

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

Combination Expansion Cohort Cohort PD-L1 Positive Basket

CPI-relapsed/refractory patients with head and neck squamous cell carcinoma, gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-105 in combination with Pembrolizumab.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Pembrolizumab

Intervention Type DRUG

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

Combination Expansion Cohort CPI Naive Non-small Cell Lung Cancer

CPI naive patients (PD-L1 IHC between 1 and 49%) will be treated with INBRX-105 in combination with Pembrolizumab.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Pembrolizumab

Intervention Type DRUG

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

Combination Expansion Cohort CPI Naive HNSCC

CPI naive patients (PD-L1 IHC \>50%) will be treated with INBRX-105 in combination with Pembrolizumab.

Group Type EXPERIMENTAL

INBRX-105 - PDL1x41BB antibody

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Pembrolizumab

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

Intervention Type DRUG

Other Intervention Names

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Keytruda

Eligibility Criteria

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Inclusion Criteria

* Parts 1 and 3 (escalation cohorts; completed): Patients with locally advanced or metastatic non-resectable solid tumors, whose disease has progressed despite standard therapy and for whom no further standard therapy exists.
* Part 2 (expansion cohorts): Patients with non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma or solid tumors amenable to paired biopsies, with locally advanced or metastatic, non-resectable disease, which has progressed despite standard therapy or for whom no standard or clinically acceptable therapy exists.
* Part 4 relapsed or refractory to CPI cohorts: NSCLC, cutaneous melanoma, HNSCC, MSI/TMB-high or MMRd solid tumors
* Part 4 CPI naive cohorts: locally advanced or metastatic, non-resectable NSCLC or HNSCC
* Refractory or relapsed to anti-PD-1 or anti-PD-L1, and anti-CTLA4 if applicable (NOTE: For all tumor types with checkpoint inhibitor approvals) with exception of the treatment naive NSCLC cohort.
* PD-L1 positivity by immunohistochemistry (IHC): Parts 1 and 3 (escalation cohorts) PD-L1 positivity is not required. Parts 2 and 4 (expansion cohorts): Combined Positive Score (CPS) or Tumor Proportion Score (TPS) above certain thresholds as defined per protocol.
* Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.

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, NHL, Hodgkin 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-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). 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). 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Inhibrx Biosciences, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Lead

Role: STUDY_DIRECTOR

Inhibrx Biosciences, Inc

Locations

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HonorHealth Research Institute

Scottsdale, Arizona, United States

Site Status

City of Hope at Irvine Lennar

Duarte, California, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

Valkyrie Clinical Trials

Los Angeles, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

University of Colorado Denver

Denver, Colorado, United States

Site Status

Emory University - Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Goshen Center for Cancer Care

Goshen, Indiana, United States

Site Status

Norton Cancer Center

Louisville, Kentucky, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

START Midwest

Grand Rapids, Michigan, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Nebraska Cancer Specialists - Grand Island

Omaha, Nebraska, United States

Site Status

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

Providence Cancer Institute

Portland, Oregon, United States

Site Status

Abramson Cancer Center - University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Abramson Cancer Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

New Experimental Therapeutics of San Antonio - NEXT Oncology

San Antonio, Texas, United States

Site Status

START Mountain Region

West Valley City, Utah, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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Ph 1 Ph 2 INBRX-105

Identifier Type: -

Identifier Source: org_study_id

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