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

NCT05054348 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IO-108-CL-001
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 24

Brief Summary

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.

Conditions

Solid Tumor, Adult

Keywords

IO-108

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Maximum plasma concentration (Cmax) of IO-108

  From the first dose of IO-108 until day 15 post-treatment

• Steady state concentration of IO-108

  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

  From the first dose until 30 days after the last treatment

• Anti-tumor activity of IO-108 and IO-108+pembrolizumab

  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

  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 Outcomes (1)

• Receptor occupancy of IO-108 in IO-108 monotherapy and IO-108+pembrolizumab

  From the first dose of IO-108 till 21 days after

Study Arms (3)

IO-108 Monotherapy

EXPERIMENTAL

Treatment of patients with advanced solid tumors with IO-108 monotherapy

Biological: IO-108

IO-108 + pembrolizumab combination therapy

EXPERIMENTAL

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 + cemiplimab combination therapy

EXPERIMENTAL

Treatment of patients with advanced solid tumors with IO-108 in combination with a fixed dose of cemiplimab

Biological: IO-108 + cemiplimab combination therapy

Interventions

IO-108 BIOLOGICAL

IO-108 given as monotherapy

IO-108 Monotherapy

IO-108 + pembrolizumab combination therapy BIOLOGICAL

IO-108 and fixed dose pembrolizumab combination therapy

Also known as: IO-108 + Keytruda combination therapy

IO-108 + pembrolizumab combination therapy

IO-108 + cemiplimab combination therapy BIOLOGICAL

IO-108 and fixed dose cemiplimab combination therapy

Also known as: IO-108 + Libtayo combination therapy

IO-108 + cemiplimab combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be ≥18.
• 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.
• Patient has measurable disease by Response Evaluation in Solid Tumors version 1.1 (RECIST 1.1) as assessed by local site.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Patients must have adequate hepatic function and renal function.

You may not qualify if:

• Patients who previously received a monoclonal antibody therapy targeting LILRB2/ Immunoglobulin-Like Transcript 4 (ILT4) (including IO-108).
• 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.
• Requires systemic corticosteroids at a dose of \>10 mg prednisone or the dose equivalent to other systemic corticosteroid.
• History of radiation pneumonitis, non-infectious pneumonitis or interstitial lung disease.
• Symptomatic CNS spread of tumor.
• History of Grade \> 3 immune-related AEs with any prior immunotherapy.
• Patients with uncontrolled, active infection.
• Patients with known hypersensitivity to any of the components of the IO-108 formulation or pembrolizumab.
• Active known malignancy with the exception of any of the following:
• Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer;
• Low-risk prostate cancer for which observation or hormonal therapy only is indicated;
• 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).
• 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).
• 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.
• Ongoing cardiac dysrhythmias of Grade 2 or higher per NCI CTCAE, Version 5.0.

Sponsors & Collaborators

• Immune-Onc Therapeutics: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (24)

Arizona Oncology Associates, PC-HOPE (140) (USOR SITE)

Tucson, Arizona, 85711, United States

Location

Beverly HIlls Cancer Center (129)

Beverly Hills, California, 90211, United States

Location

Rocky Mountain Cancer Centers, LLP (141) (USOR SITE)

Lone Tree, Colorado, 80124, United States

Location

University of Florida (125)

Gainesville, Florida, 32611, United States

Location

Florida Cancer Specialists (134)

Lake Mary, Florida, 32746, United States

Location

Memorial Cancer Institute (146)

Pembroke Pines, Florida, 33021, United States

Location

Florida Cancer Specialists & Research Institute (103)

Sarasota, Florida, 34232, United States

Location

Hematology Oncology (136)

Stuart, Florida, 34952, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer Center (123)

Indianapolis, Indiana, 46202, United States

Location

Maryland Oncology Hematology, PA (145) (USOR SITE)

Columbia, Maryland, 21044, United States

Location

Karmanos Cancer Institute (126)

Detroit, Michigan, 48201, United States

Location

St. Vincent - Frontier Cancer Center (135)

Billings, Montana, 59102, United States

Location

NYU Langone Health (131)

New York, New York, 10016, United States

Location

Carolina BioOncology (102)

Huntsville, North Carolina, 28078, United States

Location

Gabrail Cancer Center (128)

Canton, Ohio, 44718, United States

Location

Oncology Hematology Care Clinical Trials, LLC (144) (USOR SITE)

Cincinnati, Ohio, 45242, United States

Location

Providence Cancer Institute (104)

Portland, Oregon, 97213, United States

Location

UPMC Hillman Cancer Center (105)

Pittsburgh, Pennsylvania, 15209, United States

Location

Texas Oncology - Austin (142) (USOR SITE)

Austin, Texas, 78705, United States

Location

Texas Oncology - Baylor Charles A. (143) (USOR SITE)

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center (101)

Houston, Texas, 77030, United States

Location

Oncology Consultants, P.A. (138)

Houston, Texas, 77030, United States

Location

NEXT Oncology-Virginia (121)

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute (147)

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• Taylor MH, Naing A, Powderly J, Woodard P, Chung L, Lin WH, Tian H, Siemers N, Xiang H, Deng R, Hong K, Valencia D, Huang T, Zhu Y, Liao XC, Schebye XM, Patel MR. Phase I dose escalation study of IO-108, an anti-LILRB2 antibody, in patients with advanced solid tumors. J Immunother Cancer. 2024 Nov 20;12(11):e010006. doi: 10.1136/jitc-2024-010006.

  PMID: 39567210 DERIVED

Study Officials

• Wen Hong Lin, MD

  Immune-Onc Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation, dose expansion and dose randomization

Study Record Dates

• First Submitted: August 30, 2021
• First Posted: September 23, 2021
• Study Start: September 30, 2021
• Primary Completion: April 29, 2024
• Study Completion: May 31, 2024
• Last Updated: June 4, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (24)