Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

February 20, 2024 updated by: Inhibrx, Inc.

An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Multicohort, Phase 1/2 Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors

This is a Phase 1/2, open-label, non-randomized, 4-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 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

333

Phase

  • Phase 1

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
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
        • Principal Investigator:
          • Erminia Massarelli, MD
      • Los Angeles, California, United States, 90069
      • Orange, California, United States, 92868
        • Not yet recruiting
        • St. Joseph Hospital of Orange
        • Principal Investigator:
          • Timothy Byun, MD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Winship Cancer Institute - Emory University
        • Principal Investigator:
          • Conor Steuer, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • The University of Chicago Medical Center
        • Principal Investigator:
          • Daniel Olson, MD
        • Contact:
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Principal Investigator:
          • Muhammad Furqan, MD
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Cancer Institute
        • Principal Investigator:
          • John Hamm, MD
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Cancer Institute
        • Contact:
        • Principal Investigator:
          • Amy Weise, MD
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • START Midwest
        • Contact:
        • Principal Investigator:
          • Manish Sharma, MD
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Nebraska Cancer Specialists
        • Contact:
        • Principal Investigator:
          • Ralph Hauke, MD
    • Oregon
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
        • Principal Investigator:
          • Rachel Sanborn, MD
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37204
        • Recruiting
        • Vanderbilt University School of Medicine
        • Principal Investigator:
          • Elizabeth Davis, MD
        • Contact:
    • Texas
      • El Paso, Texas, United States, 79915
      • San Antonio, Texas, United States, 78229
        • Completed
        • NEXT Oncology
      • The Woodlands, Texas, United States, 77380
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists
        • Principal Investigator:
          • Alexander Spira, MD
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert Hospital and the Medical College of Wisconsin
        • Principal Investigator:
          • Jonathan Thompson, 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

Select Inclusion Criteria:

  • Males or females aged ≥18 years.
  • Parts 1 and 3 (escalation cohorts): Subjects with locally advanced or metastatic non resectable solid tumors, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.
  • Part 2 (single-agent expansion cohort): Subjects with NSCLC, melanoma, HNSCC, G/GEA, RCC, or TCC, with locally advanced or metastatic, non-resectable disease, which has progressed despite all standard therapies including CPI or for whom no standard or clinically acceptable therapy exists.
  • Part 4 (expansion cohorts in combination with pembrolizumab): Subjects with melanoma (all types), HNSCC, G/GEA, RCC, TCC, NSCLC, or MSI-high, TMB-high, MMR-deficient tumors, with locally advanced or metastatic, non resectable disease, which is either CPI-naive (melanoma, HNSCC, NPC) or progressed despite all standard therapies including CPI (NSCLC, RCC, TCC, uveal melanoma, MSI-high, TMB-high, or MMR-deficient solid tumors) or for whom no standard or clinically acceptable therapy exists.
  • All subjects with non-squamous NSCLC must have documentation of absence of tumor activating EGFR mutations and absence of ALK gene rearrangements.
  • PD-L1 by IHC (22C3): Parts 1 and 3: IHC optional. Part 2: IHC result mandatory but any score allowed. Part 4: Combined Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥50% for NSCLC; for TMB-high tumors, any TPS% is allowed).
  • Adequate hematologic, coagulation, hepatic and renal function and ECOG score as defined per protocol.

Select Exclusion Criteria:

  • Prior exposure to OX40 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 with certain exceptions.
  • Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's 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-106.
  • 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 Parts 1 and 3. 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.
  • Additional in- and exclusion criteria per protocol.

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: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1 INBRX-106 Escalation
INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors.
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
Experimental: Part 3 INBRX-106 Escalation in Combination with Pembrolizumab
INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors.
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
Drug: Pembrolizumab 200 mg
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab
Subjects with melanoma (any type), head and neck squamous cell carcinoma (non-nasopharyngeal), nasopharyngeal carcinoma, MSI-high, TMB-high or MMR-deficient tumors, will be treated with INBRX-106 in combination with 200mg pembrolizumab IV every 3 weeks.
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
Drug: Pembrolizumab 200 mg
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
Active Comparator: Part 4 Pembrolizumab Expansion Arm, Randomized
Subjects with non-small cell lung cancer will be treated with 200 mg pembrolizumab IV every 3 weeks
Drug: Pembrolizumab 200 mg
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab in NSCLC, Randomized
Subjects with non-small cell lung cancer will be treated with alternating every 6 weeks dosing of INBRX-106 0.3 mg/kg Q6W and 400 mg pembrolizumab IV
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
Drug: Pembrolizumab 400 mg
Pembrolizumab 400 mg by IV infusion given on Day 1 of alternating 21-day cycles (every 6 weeks)
Other Names:
  • Keytruda
Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab in NSCLC; Randomized
Subjects with non-small cell lung cancer will be given a 0.3 mg/kg priming dose of INBRX-106 in cycle 1, followed by 0.1 mg/kg INBRX-106 and 200 mg pembrolizumab IV every 3 weeks in subsequent cycles
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
Drug: Pembrolizumab 200 mg
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
Experimental: Part 2 INBRX-106 Escalation in NSCLC
Subjects with non-small cell carcinoma relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
Experimental: Part 2 INBRX-106 Escalation in Various Solid Tumor Types
Subjects with melanoma (any type), head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma or MSI/TMB-high tumors that are relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
Experimental: Part 4 INBRX-106 Expansion with Pembrolizumab in Uveal Melanoma
Subjects with ocular (uveal) melanoma who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
Drug: Pembrolizumab 200 mg
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda
Experimental: Part 4 INBRX-106 Expansion with Pembrolizumab in MSI-high, TMB-high or MMR-deficient tumors
Subjects with solid tumors that have confirmed MSI-high, TMB-high or MMR-deficient states who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks
Drug: INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
Drug: Pembrolizumab 200 mg
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab
Time Frame: 2-4 years
Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0
2-4 years
Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab
Time Frame: 2-4 years
Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0
2-4 years
MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab
Time Frame: 2-4 years
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-106 and INBRX-106 in combination with pembrolizumab
2-4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the serum concentration time curve (AUC) of INBRX-106
Time Frame: 2-4 years
Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
2-4 years
Maximum observed serum concentration (Cmax) of INBRX-106
Time Frame: 2-4 years
Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
2-4 years
Trough observed serum concentration (Ctrough) of INBRX-106
Time Frame: 2-4 years
Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
2-4 years
Time to Cmax (Tmax) of INBRX-106
Time Frame: 2-4 years
Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
2-4 years
Immunogenicity of INBRX-106
Time Frame: 2-4 years
Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
2-4 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab
Time Frame: 2-4 years
Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).
2-4 years
Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab
Time Frame: 2-4 years
Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).
2-4 years

Collaborators and Investigators

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

Sponsor

Inhibrx, Inc.

Collaborators

Merck Sharp & Dohme LLC

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)

December 10, 2019

Primary Completion (Estimated)

February 2, 2026

Study Completion (Estimated)

May 15, 2026

Study Registration Dates

First Submitted

December 11, 2019

First Submitted That Met QC Criteria

December 11, 2019

First Posted (Actual)

December 13, 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-106
  • MK3475 KEYNOTE A99 (Other Identifier: Merck & Co., Inc.)

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.

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