Study Stopped
Program terminated due to lack of meaningful efficacy signal.
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
1 other identifier
interventional
160
1 country
23
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2019
Longer than P75 for phase_1
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 15, 2019
CompletedFirst Posted
Study publicly available on registry
January 18, 2019
CompletedStudy Start
First participant enrolled
January 30, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 3, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 3, 2024
CompletedOctober 23, 2024
October 1, 2024
5.7 years
January 15, 2019
October 21, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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 Outcomes (5)
Area under the serum concentration time curve (AUC) of INBRX-105
Up to 2-3 years
Maximum observed serum concentration (Cmax) of INBRX-105
Up to 2-3 years
Trough observed serum concentration (Ctrough) of INBRX-105
Up to 2-3 years
Time to Cmax (Tmax) of INBRX-105
Up to 2-3 years
Immunogenicity of INBRX-105
Up to 2-3 years
Other Outcomes (1)
Anti-tumor activity of INBRX-105
Up to 2-3 years
Study Arms (11)
Single Agent Escalation
EXPERIMENTALINBRX-105 will be escalated in patients with locally advanced or metastatic solid tumors.
Expansion Cohort Non-small Cell Lung Cancer
EXPERIMENTALPatients will be treated with single-agent INBRX-105 at either the MTD or RP2D.
Expansion Cohort Melanoma
EXPERIMENTALPatients will be treated with single-agent INBRX-105 at either the MTD or RP2D.
Expansion Cohort PD-L1 Positive Basket
EXPERIMENTALPatients 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.
Expansion Cohort Nasopharyngeal or Oropharyngeal Carcinoma
EXPERIMENTALPatients with head and neck squamous cell carcinoma (NPC or OPC) will be treated with single-agent INBRX-105 at either the MTD or RP2D.
INBRX-105 Escalation in Combination with Pembrolizumab
EXPERIMENTALINBRX-105 will be escalated in combination with Pembrolizumab in pateitns with locally advanced or metastatic solid tumors.
Combination Expansion Cohort Non-small Cell Lung Cancer
EXPERIMENTALCPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.
Combination Expansion Cohort Melanoma
EXPERIMENTALCPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.
Combination Expansion Cohort Cohort PD-L1 Positive Basket
EXPERIMENTALCPI-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.
Combination Expansion Cohort CPI Naive Non-small Cell Lung Cancer
EXPERIMENTALCPI naive patients (PD-L1 IHC between 1 and 49%) will be treated with INBRX-105 in combination with Pembrolizumab.
Combination Expansion Cohort CPI Naive HNSCC
EXPERIMENTALCPI naive patients (PD-L1 IHC \>50%) will be treated with INBRX-105 in combination with Pembrolizumab.
Interventions
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 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
HonorHealth Research Institute
Scottsdale, Arizona, 85258, United States
City of Hope at Irvine Lennar
Duarte, California, 91010, United States
City of Hope
Duarte, California, 91010, United States
Valkyrie Clinical Trials
Los Angeles, California, 90069, United States
Stanford University
Palo Alto, California, 94304, United States
University of Colorado Denver
Denver, Colorado, 80045, United States
Emory University - Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Goshen Center for Cancer Care
Goshen, Indiana, 46526, United States
Norton Cancer Center
Louisville, Kentucky, 40202, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
START Midwest
Grand Rapids, Michigan, 49546, United States
Washington University
St Louis, Missouri, 63110, United States
Nebraska Cancer Specialists - Grand Island
Omaha, Nebraska, 68114, United States
Nebraska Cancer Specialists
Omaha, Nebraska, 68130, United States
Providence Cancer Institute
Portland, Oregon, 97213, United States
Abramson Cancer Center - University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Abramson Cancer Center at Pennsylvania Hospital
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37204, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
New Experimental Therapeutics of San Antonio - NEXT Oncology
San Antonio, Texas, 78229, United States
START Mountain Region
West Valley City, Utah, 84119, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Lead
Inhibrx Biosciences, Inc
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 15, 2019
First Posted
January 18, 2019
Study Start
January 30, 2019
Primary Completion
October 3, 2024
Study Completion
October 3, 2024
Last Updated
October 23, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will not share