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

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: Terminated
• Conditions: Melanoma; Renal Cell Carcinoma; Nasopharyngeal Carcinoma; Gastric Adenocarcinoma; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Esophageal Adenocarcinoma; Metastatic Solid Tumors; Oropharyngeal Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab; Drug: INBRX-105 - PDL1x41BB antibody

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • Duarte, California, United States, 91010
      • City Of Hope
    • Duarte, California, United States, 91010
      • City of Hope at Irvine Lennar
    • Los Angeles, California, United States, 90069
      • Valkyrie Clinical Trials
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado Denver
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University - Winship Cancer Institute
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Goshen Center for Cancer Care
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists
    • Omaha, Nebraska, United States, 68114
      • Nebraska Cancer Specialists - Grand Island
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center - University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center at Pennsylvania Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • New Experimental Therapeutics of San Antonio - NEXT Oncology
  • Utah
    • West Valley City, Utah, United States, 84119
      • START Mountain Region
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

11

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	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	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	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	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	Maximum observed serum concentration (Cmax) of INBRX-105 will be determined.	Up to 2-3 years
Trough observed serum concentration (Ctrough) of INBRX-105	Trough observed serum concentration (Cmax) of INBRX-105 will be determined.	Up to 2-3 years
Time to Cmax (Tmax) of INBRX-105	Time to Cmax (Tmax) of INBRX-105 will be determined.	Up to 2-3 years
Immunogenicity of INBRX-105	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	Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).	Up to 2-3 years

Collaborators and Investigators

• Sponsor: Inhibrx Biosciences, Inc
• Investigators: Study Director: Clinical Lead, Inhibrx Biosciences, Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2019
• Primary Completion (Actual): October 3, 2024
• Study Completion (Actual): October 3, 2024

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 (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Lung Cancer; Urothelial Carcinoma; Gastric Cancer; Pembrolizumab; Melanoma; PD-L1; Keytruda; Solid Tumors; PDL1; Kidney Cancer; Renal cell carcinoma; Stomach Cancer; Renal Cancer; Nasopharyngeal carcinoma; 4-1BB; 41BB; Oropharyngeal carcinoma
• Additional Relevant MeSH Terms: Urogenital Diseases; Stomatognathic Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Skin Diseases; Urologic Neoplasms; Otorhinolaryngologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Neuroendocrine Tumors; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Squamous Cell; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Renal Cell; Adenocarcinoma; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Pembrolizumab; Antibodies
• 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