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Dose Escalation Study of IO-108 and IO-108+Pembrolizumab in Solid Tumors

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ClinicalTrials.gov Identifier: NCT05054348
Recruitment Status : Not yet recruiting
First Posted : September 23, 2021
Last Update Posted : October 5, 2021
Sponsor:
Information provided by (Responsible Party):
Immune-Onc Therapeutics Inc

Brief Summary:
To assess safety and tolerability of increasing doses of IO-108 either as monotherapy or in combination with pembrolizumab in patients with advanced solid tumors, and select the recommended Phase 2 dose (RP2D).

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Biological: IO-108 Biological: IO-108 + pembrolizumab combination therapy Phase 1

Detailed Description:
This is a Phase 1, open-label, multicenter, dose-escalation study of IO-108 as monotherapy and in combination with pembrolizumab, in adult subjects with advanced relapsed or refractory solid tumors to estimate the maxium tolerated dose (MTD) or maximum administered dose (MAD) to select the RP2D, and to study safety, tolerability, pharmacokinetic, pharmacodynamics and clinical activity of IO-108 as monotherapy or in combination with pembrolizumab.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of IO-108 as Monotherapy and in Combination With Pembrolizumab, in Adult Subjects With Advanced Relapsed or Refractory Solid Tumors
Estimated Study Start Date : September 25, 2021
Estimated Primary Completion Date : May 30, 2022
Estimated Study Completion Date : November 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IO-108 Monotherapy
increasing dose levels of IO-108
Biological: IO-108
IO-108 given as monotherapy

Experimental: IO-108 + pembrolizumab combination therapy
increasing dose levels of IO-108 in combination with a fixed dose of pembrolizumab
Biological: IO-108 + pembrolizumab combination therapy
IO-108 and fixed dose pembrolizumab combination therapy
Other Name: IO-108 + Keytruda combination therapy




Primary Outcome Measures :
  1. Incidence of treatment-emergent and serious adverse events in patients treated with IO-108 and IO-108+pembrolizumab [ Time Frame: From first dose of IO-108 until the end of treatment which is up to 2 years from the first treatment date ]
    safety and tolerability as measured by the incidence of treatment-emergent adverse events and serious adverse events

  2. Determine MTD (maximum tolerated dose) through assessment of dose-limiting toxicities (DLT) [ Time Frame: From the first dose of IO-108 until 21 days post-treatment ]
    MTD will be determined through observation of pre-determined DLTs in each dose cohort


Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) of IO-108 [ Time Frame: From the first dose of IO-108 until day 15 post-treatment ]
    Characterize the Cmax of IO-108 by successive sampling of blood at pre-specified time points

  2. Steady state concentration of IO-108 [ Time Frame: From the second dose of IO-108 until the last treatment which is up to 2 years from the first treatment date ]
    Characterize steady state concentration of IO-108 by successive sampling of blood at pre-specified time points

  3. Immunogenicity of IO-108 and IO-108+pembrolizumab [ Time Frame: From the first dose until 30 days after the last treatment ]
    Determine the incidence/titer of anti-drug antibodies (ADAs) against IO-108 and pembrolizumab (in combination treatment)

  4. Anti-tumor activity of IO-108 and IO-108+pembrolizumab [ Time Frame: From the date of first treatment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to estimated period of 48 months ]
    Determine preliminary rates of response after treatment with IO-108


Other Outcome Measures:
  1. Receptor occupancy of IO-108 in IO-108 monotherapy and IO-108+pembrolizumab [ Time Frame: From the first dose of IO-108 till 21 days after ]
    To assess target engagement via determining Leukocyte Immunoglobulin-Like Receptor subfamily B2 (LILRB2) occupancy by IO-108 in peripheral blood myeloid cells, as expressed by % of target receptor engagement



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be ≥18.
  2. Has any histologically- or cytologically confirmed advanced/metastatic solid tumor by pathology report and has received, has been intolerant to, or has been ineligible for standard systemic therapy known to confer clinical benefit. Solid tumors of any type are eligible for enrollment. Patients with asymptomatic central nervous system (CNS) disease may be enrolled.
  3. Patient has measurable disease by Response Evaluation in Solid Tumors version 1.1 (RECIST 1.1) as assessed by local site.
  4. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  5. Patients must have adequate hepatic function and renal function.

Exclusion Criteria:

  1. Patients who previously received a monoclonal antibody therapy targeting LILRB2/ Immunoglobulin-Like Transcript 4 (ILT4) (including IO-108).
  2. Patients who received a biologic systemic anti-cancer therapy <4 weeks or 5 half-lives prior to their first day of study drug administration, or a small molecule systemic anti-cancer therapy or definitive radiotherapy <2 weeks or 5 half-lives prior to their first day of study drug administration or have not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1 or better from any adverse events (AEs) that were due to prior cancer therapeutics. Palliative radiation is allowed within 2 weeks of the first day of study drug administration.
  3. Requires systemic corticosteroids at a dose of >10 mg prednisone or the dose equivalent to other systemic corticosteroid.
  4. History of radiation pneumonitis, non-infectious pneumonitis or interstitial lung disease.
  5. Symptomatic CNS spread of tumor.
  6. History of Grade ≥3 immune-related AEs with any prior immunotherapy.
  7. Patients with uncontrolled, active infection.
  8. Patients with known hypersensitivity to any of the components of the IO-108 formulation or pembrolizumab.
  9. Active known malignancy with the exception of any of the following:

    1. Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer;
    2. Low-risk prostate cancer for which observation or hormonal therapy only is indicated;
    3. Any other malignancy treated with curative intent with the last treatment completed ≥6 months before study initiation (with the exception of hormonal therapies when indicated).
  10. Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) or left ventricular ejection fraction (LVEF) <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan ≤28 days prior to Cycle 1 Day 1 (C1D1).
  11. Any of the following in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsades de pointes, clinically significant arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), and left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF (NYHA class III or IV), cerebrovascular accident, transient ischemic attack, or pulmonary embolism. Patients with asymptomatic right bundle branch block or controlled atrial fibrillation are allowed.
  12. Ongoing cardiac dysrhythmias of Grade 2 or higher per NCI CTCAE, Version 5.0.
  13. Known active bacterial, viral, and/or fungal infection including hepatitis B (HBV), hepatitis C, human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) or acquired immunodeficiency syndrome (AIDS)-related illness.
  14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05054348


Contacts
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Contact: Luke Chung, MD, MPH +1 3392156509 luke.chung@immuneonc.com
Contact: Elizabeth Wieland elizabeth.wieland@immuneonc.com

Locations
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United States, North Carolina
Carolina BioOncology
Huntsville, North Carolina, United States, 28078
Contact: Jaelyn Linski    980-441-1015    jlinski@carolinabiooncology.org   
Contact: Ashley McClain    9804411021    amcclain@carolinabiooncology.org   
Principal Investigator: John Powderly, MD         
United States, Oregon
Providence Cancer Institute
Portland, Oregon, United States, 97213
Contact    503-215-2614    Orcanrsrchstudies@providence.org   
Principal Investigator: Matthew Taylor, MD         
Sponsors and Collaborators
Immune-Onc Therapeutics Inc
Investigators
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Study Director: Luke Chung, MD, MPH Immune-Onc Therapeutics
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Responsible Party: Immune-Onc Therapeutics Inc
ClinicalTrials.gov Identifier: NCT05054348    
Other Study ID Numbers: IO-108-CL-001
First Posted: September 23, 2021    Key Record Dates
Last Update Posted: October 5, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Immune-Onc Therapeutics Inc:
IO-108
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents