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TerminatedNCT03809624PDL1x41BBUpdated Oct 23, 2024

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

A Phase 1 interventional study of INBRX-105 - PDL1x41BB antibody and Pembrolizumab in Metastatic Solid Tumors, Non-small Cell Lung Cancer and Melanoma, sponsored by Inhibrx Biosciences, Inc. Terminated at 23 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-23.

Sponsored by Inhibrx Biosciences, Inc · Phase 1, Interventional, and Treatment

Why this study was terminated
Program terminated due to lack of meaningful efficacy signal.
Phase
Phase 1
Study type
Interventional
Enrollment
160
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • 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

Keywords

  • Solid Tumors
  • Lung Cancer
  • Melanoma
  • Head and Neck Cancer
  • Stomach Cancer
  • Gastric Cancer
  • Kidney Cancer
  • Renal cell carcinoma
  • Renal Cancer
  • Urothelial Carcinoma
  • PDL1
  • 41BB
  • PD-L1
  • 4-1BB
  • Pembrolizumab
  • Keytruda
  • Nasopharyngeal carcinoma
  • Oropharyngeal carcinoma
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
160 participants (actual)

Study arms

  • Experimental
    Single Agent Escalation

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

    Drug: INBRX-105 - PDL1x41BB antibody

  • 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

  • Experimental
    Expansion Cohort Melanoma

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

    Drug: INBRX-105 - PDL1x41BB antibody

  • 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

  • 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

  • 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: INBRX-105 - PDL1x41BB antibody · Drug: Pembrolizumab

  • Experimental
    Combination Expansion Cohort Non-small Cell Lung Cancer

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

    Drug: INBRX-105 - PDL1x41BB antibody · Drug: Pembrolizumab

  • Experimental
    Combination Expansion Cohort Melanoma

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

    Drug: INBRX-105 - PDL1x41BB antibody · Drug: Pembrolizumab

  • 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: INBRX-105 - PDL1x41BB antibody · Drug: Pembrolizumab

  • 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: INBRX-105 - PDL1x41BB antibody · Drug: Pembrolizumab

  • 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

Interventions

  • DrugINBRX-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.

  • DrugPembrolizumab

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

    Also known as: Keytruda

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Up to 2-3 years

  2. 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.

    Time frame: Up to 2-3 years

  3. 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.

    Time frame: Up to 2-3 years

Secondary outcomes

  1. 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.

    Time frame: Up to 2-3 years

  2. Maximum observed serum concentration (Cmax) of INBRX-105

    Maximum observed serum concentration (Cmax) of INBRX-105 will be determined.

    Time frame: Up to 2-3 years

  3. Trough observed serum concentration (Ctrough) of INBRX-105

    Trough observed serum concentration (Cmax) of INBRX-105 will be determined.

    Time frame: Up to 2-3 years

  4. Time to Cmax (Tmax) of INBRX-105

    Time to Cmax (Tmax) of INBRX-105 will be determined.

    Time frame: Up to 2-3 years

  5. Immunogenicity of INBRX-105

    Frequency of anti-drug antibodies (ADA) against INBRX-105 will be determined.

    Time frame: Up to 2-3 years

Other outcomes

  1. Anti-tumor activity of INBRX-105

    Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).

    Time frame: Up to 2-3 years

06

Study locations

23 sites
  • 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
    Saint 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
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03809624
Lead sponsor
Inhibrx Biosciences, Inc
Responsible party
Sponsor
First posted
Jan 18, 2019
Start date
Jan 30, 2019
Primary completion
Oct 3, 2024
Completion
Oct 3, 2024
Last update
Oct 23, 2024

Study contacts

Clinical Lead
study director · Inhibrx Biosciences, Inc

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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