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Dose-Escalation and Dose-Expansion Study of IO-202 and IO-202+Pembrolizumab in Solid Tumors

I

Immune-Onc Therapeutics

Status and phase

Completed
Phase 1

Conditions

Solid Tumor, Adult

Treatments

Biological: IO-202
Biological: RP2D of IO-202 + pembrolizumab combination therapy in multiple solid tumor types
Biological: IO-202 + pembrolizumab combination therapy

Study type

Interventional

Funder types

Industry

Identifiers

NCT05309187
IO-202-CL-002

Details and patient eligibility

About

To assess safety and tolerability of increasing doses of IO-202 either as monotherapy or in combination with pembrolizumab in patients with advanced solid tumors, and select the recommended Phase 2 dose (RP2D).

Full description

This is a Phase 1, open-label, multicenter, dose-escalation and dose-expansion study of IO-202 in adult subjects with advanced relapsed or refractory solid tumors to study safety, tolerability, pharmacokinetic, pharmacodynamics and clinical activity of IO-202 as monotherapy or in combination with pembrolizumab and to estimate the maximum tolerated dose (MTD) or maximum administered dose (MAD), and to select the RP2D.

Enrollment

22 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Subject must be ≥18 years old.
  2. Part 1 - Dose Escalation: Subject must have any histologically or cytologically confirmed advanced or metastatic solid tumor and has received, has been intolerant to, or has been ineligible for standard systemic therapy known to confer clinical benefit.
  3. Part 2 - Dose Expansion: Subject must have failed at least one available therapy for the disease under study.
  4. Subject must have measurable disease per RECIST 1.1 as assessed by local clinical site.
  5. Subject must have an Eastern Cooperative Oncology Group performance status of 0 or 1.

Exclusion criteria

  1. Subject who previously received leukocyte immunoglobulin-like receptor subfamily B (LILRB) or immunoglobulin-like transcript [ILT]) targeting agents including those targeting LILRB1 (ILT2), LILRB2 (ILT4), LILRB4 (ILT3), or leukocyte-associated immunoglobulin-like receptor 1 (LAIR1).

  2. Subject 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.

  3. Subject has symptomatic central nervous system (CNS) tumor.

  4. Requires systemic corticosteroids at a dose of >10 mg prednisone or the dose equivalent of other systemic corticosteroid.

  5. History of radiation pneumonitis, non-infectious pneumonitis or interstitial lung disease.

  6. History of Grade ≥3 immune-related AEs with any prior immunotherapy.

  7. Subjects with known hypersensitivity to any of the components of the IO-202 formulation or pembrolizumab.

  8. 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).
  9. Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) or left ventricular ejection fraction (LVEF) <40% by ECHO or multi-gated acquisition (MUGA) scan ≤28 days prior to Cycle 1 Day 1 (C1D1).

  10. 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.

  11. Ongoing cardiac dysrhythmias of Grade 2 or higher per NCI CTCAE, Version 5.0.

  12. 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.

  13. Subjects with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the subject before study entry.

  14. Subject with current active treatment in another interventional therapeutic clinical study.

  15. 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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

22 participants in 3 patient groups

IO-202 Monotherapy (dose escalation)
Experimental group
Treatment:
Biological: IO-202
IO-202 dose escalation + pembrolizumab
Experimental group
Description:
Increasing dose levels of IO-202 with fixed dose of pembrolizumab
Treatment:
Biological: IO-202 + pembrolizumab combination therapy
IO-202 + pembrolizumab combination therapy (dose expansion)
Experimental group
Description:
RP2D + pembrolizumab combination therapy in solid tumor cohorts
Treatment:
Biological: RP2D of IO-202 + pembrolizumab combination therapy in multiple solid tumor types

Trial contacts and locations

10

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Central trial contact

Roya Nawabi, MBA; Wen Hong Lin, MD

Data sourced from clinicaltrials.gov

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