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Metastatic Solid TumorsPhase 1PDL1x41BBNCT03809624

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

A Phase 1 study testing INBRX-105 - PDL1x41BB antibody and Pembrolizumab in people with Metastatic Solid Tumors and Non-small Cell Lung Cancer, run by Inhibrx Biosciences, Inc at 23 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
INBRX-105 - PDL1x41BB antibody and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
23 sitesUnited States
Study dates
30 Jan 2019to 3 Oct 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

United States23 sites

  • Emory University - Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Colorado Denver

    Denver, Colorado, 80045

  • City of Hope at Irvine Lennar

    Duarte, California, 91010

  • City of Hope

    Duarte, California, 91010

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Goshen Center for Cancer Care

    Goshen, Indiana, 46526

  • START Midwest

    Grand Rapids, Michigan, 49546

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Valkyrie Clinical Trials

    Los Angeles, California, 90069

  • Norton Cancer Center

    Louisville, Kentucky, 40202

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37204

  • Nebraska Cancer Specialists - Grand Island

    Omaha, Nebraska, 68114

  • Nebraska Cancer Specialists

    Omaha, Nebraska, 68130

  • Stanford University

    Palo Alto, California, 94304

  • Abramson Cancer Center - University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Abramson Cancer Center at Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19104

  • Providence Cancer Institute

    Portland, Oregon, 97213

  • New Experimental Therapeutics of San Antonio - NEXT Oncology

    San Antonio, Texas, 78229

  • HonorHealth Research Institute

    Scottsdale, Arizona, 85258

  • Washington University

    St Louis, Missouri, 63110

  • Northwest Medical Specialties, PLLC

    Tacoma, Washington, 98405

  • START Mountain Region

    West Valley City, Utah, 84119

Other trials in United States

About this study

Official title: 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.

Being tested
INBRX-105 - PDL1x41BB antibody, Pembrolizumab
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
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Melanoma, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Renal Cell, Adenocarcinoma Of Esophagus, Nasopharyngeal Carcinoma, Oropharyngeal Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • INBRX-105 - PDL1x41BB antibodyDrug

    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.

  • PembrolizumabDrug

    Also called Keytruda

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

Study groups in NCT03809624
Study groupRoleWhat they receive
Single Agent EscalationExperimentalINBRX-105 will be escalated in patients with locally advanced or metastatic solid tumors.
Receives: Drug: INBRX-105 - PDL1x41BB antibody
Expansion Cohort Non-small Cell Lung CancerExperimentalPatients will be treated with single-agent INBRX-105 at either the MTD or RP2D.
Receives: Drug: INBRX-105 - PDL1x41BB antibody
Expansion Cohort MelanomaExperimentalPatients will be treated with single-agent INBRX-105 at either the MTD or RP2D.
Receives: Drug: INBRX-105 - PDL1x41BB antibody
Expansion Cohort PD-L1 Positive BasketExperimentalPatients 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.
Receives: Drug: INBRX-105 - PDL1x41BB antibody
Expansion Cohort Nasopharyngeal or Oropharyngeal CarcinomaExperimentalPatients with head and neck squamous cell carcinoma (NPC or OPC) will be treated with single-agent INBRX-105 at either the MTD or RP2D.
Receives: Drug: INBRX-105 - PDL1x41BB antibody
INBRX-105 Escalation in Combination with PembrolizumabExperimentalINBRX-105 will be escalated in combination with Pembrolizumab in pateitns with locally advanced or metastatic solid tumors.
Receives: Drug: INBRX-105 - PDL1x41BB antibody; Drug: Pembrolizumab
Combination Expansion Cohort Non-small Cell Lung CancerExperimentalCPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.
Receives: Drug: INBRX-105 - PDL1x41BB antibody; Drug: Pembrolizumab
Combination Expansion Cohort MelanomaExperimentalCPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab.
Receives: Drug: INBRX-105 - PDL1x41BB antibody; Drug: Pembrolizumab
Combination Expansion Cohort Cohort PD-L1 Positive BasketExperimentalCPI-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.
Receives: Drug: INBRX-105 - PDL1x41BB antibody; Drug: Pembrolizumab
Combination Expansion Cohort CPI Naive Non-small Cell Lung CancerExperimentalCPI naive patients (PD-L1 IHC between 1 and 49%) will be treated with INBRX-105 in combination with Pembrolizumab.
Receives: Drug: INBRX-105 - PDL1x41BB antibody; Drug: Pembrolizumab
Combination Expansion Cohort CPI Naive HNSCCExperimentalCPI naive patients (PD-L1 IHC >50%) will be treated with INBRX-105 in combination with Pembrolizumab.
Receives: Drug: INBRX-105 - PDL1x41BB antibody

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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.

    Measured: 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.

    Measured: Up to 2-3 years

Secondary outcomes (5)

  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.

    Measured: 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.

    Measured: 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.

    Measured: Up to 2-3 years

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

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

    Measured: Up to 2-3 years

  5. Immunogenicity of INBRX-105

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

    Measured: Up to 2-3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2019
  2. Study start30 Jan 2019
  3. Primary completion3 Oct 2024
  4. Study completion3 Oct 2024

Why it stopped: Program terminated due to lack of meaningful efficacy signal.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03809624
Sponsor's protocol ID
Ph 1 Ph 2 INBRX-105
Acronym
PDL1x41BB
Status last verified
Oct 2024
First submitted
15 Jan 2019
Last updated
23 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Park JC, Berz D, Sharma MR, Malhotra J, Tolcher AW, Hauke RJ, Call JA, Hamm JT, Sanborn RE, Haas NB, Tsai F, Adkins DR, Camidge DR, Spira AI, Senne L, Kalabus J, O'Neill B, Kinkead H, Garcia J, Massarelli E. Phase 1 Study of INBRX-105, a TNFRSF9 (4-1BB) and PD-L1 Bispecific Antibody, in Patients with Select Solid Tumors. Cancer Res Commun. 2026 Feb 1;6(2):374-382. doi: 10.1158/2767-9764.CRC-25-0577. Epub 2026 Jan 27.

    PubMed 41724817

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing INBRX-105 - PDL1x41BB antibody and Pembrolizumab in people with Metastatic Solid Tumors and Non-small Cell Lung Cancer, run by Inhibrx Biosciences, Inc at 23 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Program terminated due to lack of meaningful efficacy signal.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of adverse events of INBRX-105 (time frame: Up to 2-3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03809624, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2024.

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