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

A Phase 1, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study of IO-202 in Combination With Pembrolizumab in Subjects With Advanced, Relapsed, or Refractory Solid Tumors

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).

Study Overview

• Status: Completed
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Biological: IO-202; Biological: IO-202 + pembrolizumab combination therapy; Biological: RP2D of IO-202 + pembrolizumab combination therapy in multiple solid tumor types

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC-Norris Comprehensive Cancer Center (119)
  • Florida
    • Gainesville, Florida, United States, 32610-0278
      • University of Florida (125)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University - Feinberg School of Medicine (133)
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University (123)
  • New York
    • New York, New York, United States, 10029
      • Tisch Mount Sinai (124)
  • North Carolina
    • Huntsville, North Carolina, United States, 28078
      • Carolina BioOncology (102)
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute/Tennessee Oncology (122)
  • Texas
    • Dallas, Texas, United States, 75251
      • Mary Crowley Cancer Research (108)
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center (101)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Oncology Virginia (121)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IO-202 Monotherapy (dose escalation)	Biological: IO-202; IO-202 given as monotherapy
Experimental: IO-202 dose escalation + pembrolizumab; Increasing dose levels of IO-202 with fixed dose of pembrolizumab	Biological: IO-202 + pembrolizumab combination therapy; IO-202 and fixed dose pembrolizumab combination therapy; Other Names: IO-202 + Keytruda combination therapy
Experimental: IO-202 + pembrolizumab combination therapy (dose expansion); RP2D + pembrolizumab combination therapy in solid tumor cohorts	Biological: RP2D of IO-202 + pembrolizumab combination therapy in multiple solid tumor types; Expansion cohorts of the RP2D of IO-202 and fixed dose pembrolizumab combination therapy in multiple tumor types.; Other Names: RP2D of IO-202 + Keytruda combination therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent and serious adverse events in patients treated with IO-202 and IO-202 + pembrolizumab	safety and tolerability as measured by the incidence of treatment-emergent adverse events.	From first dose of IO-202 until the end of treatment which is up to 2 years from the first treatment date
Dose-limiting toxicities (DLTs) with IO-202 and IO-202 + pembrolizumab	DLTs as measured by the incidence during Cycle 1.	From the first dose of IO-202 and IO-202 + pembrolizumab until 21 days after 1st treatment
Study discontinuations due to adverse events (AEs)	The number of study discontinuations due to AEs	From the first dose of IO-202 IO-202 and IO-202 + pembrolizumab up to 2 years from the first treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum serum concentration (Cmax) of IO-202	Characterize the Cmax of IO-202 by successive sampling of blood at pre-specified times	From the first dose of IO-202 until Cycle 5, Day 1
Minimum concentration of IO-202	Characterize minimum concentration of IO-202 by successive sampling of blood at pre-specified time points	From the first dose of IO-202 until the last treatment which is up to 2 years from the first treatment date
Immunogenicity of IO-202 and IO-202 + pembrolizumab	Determine the incidence/titer of anti-drug antibodies (ADAs) against IO-202 and pembrolizumab (in combination treatment)	From the first dose until 24 months after the last treatment
Anti-tumor activity of IO-202 and IO-202 + pembrolizumab	Determine preliminary rates of response after treatment with IO-202	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 an estimated period of 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Receptor occupancy in IO-202 monotherapy and IO-202 + pembrolizumab	To assess target engagement via determining Leukocyte Immunoglobulin-Like Receptor subfamily B4 (LILRB4) occupancy by IO-202 in peripheral blood myeloid cells, as expressed by % of target receptor engagement.	From the first dose of IO-202 till 21 days after

Collaborators and Investigators

• Sponsor: Immune-Onc Therapeutics
• Investigators: Study Director: Roya Nawabi, MBA, Immune-Onc Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2022
• Primary Completion (Actual): March 29, 2024
• Study Completion (Actual): May 31, 2024

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: May 31, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: IO-202
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: IO-202-CL-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No