Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors Including Head and Neck Cancer (PDL1x41BB)

February 20, 2024 updated by: Inhibrx, Inc.

An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 / 2 Study of INBRX-105 and INBRX-105 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • HonorHealth Research Institute
        • Principal Investigator:
          • Tsai Frank, MD
        • Contact:
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
        • Principal Investigator:
          • Erminia Massarelli, MD
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope at Irvine Lennar
        • Principal Investigator:
          • Erminia Massarelli, MD
        • Contact:
      • Los Angeles, California, United States, 90069
      • Palo Alto, California, United States, 94304
        • Not yet recruiting
        • Stanford University
        • Principal Investigator:
          • Dimitrios Colevas, MD
    • Colorado
      • Denver, Colorado, United States, 80045
        • Completed
        • University of Colorado Denver
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University - Winship Cancer Institute
        • Contact:
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Recruiting
        • Goshen Center for Cancer Care
        • Contact:
        • Principal Investigator:
          • Ebenezer Kio, MD
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Cancer Center
        • Principal Investigator:
          • John Hamm, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Jong Chul Park, MD
        • Contact:
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • Start Midwest
        • Contact:
        • Principal Investigator:
          • Manish Sharma, MD
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University
        • Principal Investigator:
          • Douglas Adkins, MD
        • Contact:
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Nebraska Cancer Specialists
        • Contact:
        • Principal Investigator:
          • Ralph Hauke, MD
      • Omaha, Nebraska, United States, 68114
        • Recruiting
        • Nebraska Cancer Specialists - Grand Island
        • Principal Investigator:
          • Ralph Hauke, MD
    • Oregon
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Cancer Institute
        • Principal Investigator:
          • Rachel Sanborn, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia, Pennsylvania, United States, 19104
    • Tennessee
      • Nashville, Tennessee, United States, 37204
        • Not yet recruiting
        • Vanderbilt University Medical Center
        • Principal Investigator:
          • Jennifer Choe, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • David Hong, MD
      • San Antonio, Texas, United States, 78229
        • Active, not recruiting
        • New Experimental Therapeutics of San Antonio - NEXT Oncology
    • Utah
      • West Valley City, Utah, United States, 84119
        • Recruiting
        • START Mountain Region
        • Principal Investigator:
          • Justin Call, MD
        • Contact:
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists
        • Principal Investigator:
          • Alexander Spira, MD
        • Contact:
    • Washington
      • Tacoma, Washington, United States, 98405
        • Not yet recruiting
        • Northwest Medical Specialties, PLLC
        • Principal Investigator:
          • Jorge Chaves, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Agent Escalation
INBRX-105 will be escalated in patients with locally advanced or metastatic solid tumors.
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
Patients 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
Patients 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 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.
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: 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.
Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
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: 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.
Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
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: Combination Expansion Cohort CPI Naive HNSCC
CPI naive patients (PD-L1 IHC >50%) will be treated with INBRX-105 in combination with Pembrolizumab.
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 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.
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: Combination Expansion Cohort Non-small Cell Lung Cancer
CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.
Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
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: Combination Expansion Cohort Melanoma
CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.
Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
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: 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.
Drug: Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 2-3 years
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.
Up to 2-3 years
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.
Up to 2-3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 2-3 years
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.
Up to 2-3 years
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.
Up to 2-3 years
Time to Cmax (Tmax) of INBRX-105
Time Frame: Up to 2-3 years
Time to Cmax (Tmax) of INBRX-105 will be determined.
Up to 2-3 years
Immunogenicity of INBRX-105
Time Frame: Up to 2-3 years
Frequency of anti-drug antibodies (ADA) against INBRX-105 will be determined.
Up to 2-3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Up to 2-3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inhibrx, Inc.

Investigators

  • Study Director: Josep Garcia, PhD, Inhibrx, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2019

Primary Completion (Estimated)

August 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

January 15, 2019

First Submitted That Met QC Criteria

January 16, 2019

First Posted (Actual)

January 18, 2019

Study Record Updates

Last Update Posted (Estimated)

February 21, 2024

Last Update Submitted That Met QC Criteria

February 20, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ph 1 Ph 2 INBRX-105

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Melanoma

Clinical Trials on Pembrolizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Trinidad & Tobago

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe