First-in-human Study of IO-108 as Single Agent and in Combination With a PD-1 Immune Check Point Inhibitor in Patients With Advanced Solid Tumors

A Phase 1b, Open-Label, Dose-Escalation, Dose-Expansion, and Dose-Randomization Study of IO 108 as Monotherapy and in Combination With Either Pembrolizumab or Cemiplimab in Adult Patients With Advanced Solid Tumors

The goal of the clinical trial is to learn about safety, tolerability and preliminary efficacy of IO-108 as monotherapy or in combination with a PD-1 inhibitor in patients with advanced, metastatic solid tumors, and to find a dose of IO-108 that is safe and efficacious to be tested in patients with various solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Biological: IO-108; Biological: IO-108 + pembrolizumab combination therapy; Biological: IO-108 + cemiplimab combination therapy

Detailed Description

In the Part 1 Dose Escalation, safety and tolerability of varying doses of IO-108 as monotherapy or in combination with pembrolizumab will be studied, in order to determine a proposed RP2D. In Part 2 Dose Expansion, patients with various types of solid tumors will be dosed with either IO-108 alone or in combination with either pembrolizumab or cemiplimab in order to study safety, tolerability and preliminary efficacy of IO-108 monotherapy and combination with a PD-1 inhibitor. In Part 3, a tumor type that has been studied in the Dose Expansion will be selected and patients will be randomized into 2 doses of IO-108 in order to explore safety, toxicity, efficacy relationship with exposure, in order to explore different doses of IO-108 that is safe and efficacious. Safety, PK, PD biomarkers and efficacy will be studied.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates, PC-HOPE (140) (USOR SITE)
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly HIlls Cancer Center (129)
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers, LLP (141) (USOR SITE)
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida (125)
    • Lake Mary, Florida, United States, 32746
      • Florida Cancer Specialists (134)
    • Pembroke Pines, Florida, United States, 33021
      • Memorial Cancer Institute (146)
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists & Research Institute (103)
    • Stuart, Florida, United States, 34952
      • Hematology Oncology (136)
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Comprehensive Cancer Center (123)
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, PA (145) (USOR SITE)
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute (126)
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent - Frontier Cancer Center (135)
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health (131)
  • North Carolina
    • Huntsville, North Carolina, United States, 28078
      • Carolina BioOncology (102)
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center (128)
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Clinical Trials, LLC (144) (USOR SITE)
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute (104)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15209
      • UPMC Hillman Cancer Center (105)
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology - Austin (142) (USOR SITE)
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. (143) (USOR SITE)
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center (101)
    • Houston, Texas, United States, 77030
      • Oncology Consultants, P.A. (138)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Oncology-Virginia (121)
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute (147)

Participation Criteria

Eligibility Criteria

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

Description

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.

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-108 Monotherapy; Treatment of patients with advanced solid tumors with IO-108 monotherapy	Biological: IO-108; IO-108 given as monotherapy
Experimental: IO-108 + pembrolizumab combination therapy; Treatment of patients with advanced solid tumors with 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 Names: IO-108 + Keytruda combination therapy
Experimental: IO-108 + cemiplimab combination therapy; Treatment of patients with advanced solid tumors with IO-108 in combination with a fixed dose of cemiplimab	Biological: IO-108 + cemiplimab combination therapy; IO-108 and fixed dose cemiplimab combination therapy; Other Names: IO-108 + Libtayo 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-108 and IO-108+pembrolizumab	safety and tolerability as measured by the incidence of treatment-emergent adverse events and serious adverse events	From first dose of IO-108 until the end of treatment which is up to 2 years from the first treatment date or disease progression whichever is earlier
Determine MTD (maximum tolerated dose) through assessment of dose-limiting toxicities (DLT)	MTD will be determined through observation of pre-determined DLTs in each dose cohort	From the first dose of IO-108 until 21 days post-treatment
Assess safety and tolerability of the IO-108 RP2D as monotherapy or in combination with either pembrolizumab or cemiplimab in patients with solid tumors	safety and tolerability as measured by the incidence of treatment-emergent adverse events and discontinuation due to TEAEs	From the first dose of IO-108 until the end of treatment which is up to 2 years from the first treatment or disease progression, whicheer is earlier

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) of IO-108	Characterize the Cmax of IO-108 by successive sampling of blood at pre-specified time points	From the first dose of IO-108 until day 15 post-treatment
Steady state concentration of IO-108	Characterize steady state concentration of IO-108 by successive sampling of blood at pre-specified time points	From the second dose of IO-108 until the last treatment which is up to 2 years from the first treatment date
Immunogenicity of IO-108 and IO-108+pembrolizumab	Determine the incidence/titer of anti-drug antibodies (ADAs) against IO-108 and pembrolizumab (in combination treatment)	From the first dose until 30 days after the last treatment
Anti-tumor activity of IO-108 and IO-108+pembrolizumab	Determine preliminary rates of response after treatment with IO-108	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 disease control rates of IO-108 as monotherapy or in combination with either pembrolizumab or cemiplimab	Disease control rate is defined as the percentage of patients with complete response, partial response or stable disease maintained for at least 3 months	From the first dose of IO-108 until the last treatment which is up to 2 years from the first treatment or disease progression whichever is earlier

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Receptor occupancy of IO-108 in IO-108 monotherapy and IO-108+pembrolizumab	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	From the first dose of IO-108 till 21 days after

Collaborators and Investigators

• Sponsor: Immune-Onc Therapeutics
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Study Director: Wen Hong Lin, MD, Immune-Onc Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): April 29, 2024
• Study Completion (Actual): May 31, 2024

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): September 23, 2021

Study Record Updates

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

More Information

Terms related to this study

• Keywords: IO-108
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Cemiplimab
• Other Study ID Numbers: IO-108-CL-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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