Clinical trial NCT05054348: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor, Adult
Keywords: IO-108
Lead sponsor: Immune-Onc Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2021-09-23
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dose escalation, dose expansion and dose randomization
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Incidence of treatment-emergent and serious adverse events in patients treated with IO-108 and IO-108+pembrolizumab
timeFrame: 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
measure: Determine MTD (maximum tolerated dose) through assessment of dose-limiting toxicities (DLT)
timeFrame: From the first dose of IO-108 until 21 days post-treatment
measure: Assess safety and tolerability of the IO-108 RP2D as monotherapy or in combination with either pembrolizumab or cemiplimab in patients with solid tumors
timeFrame: 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:
measure: Maximum plasma concentration (Cmax) of IO-108
timeFrame: From the first dose of IO-108 until day 15 post-treatment
measure: Steady state concentration of IO-108
timeFrame: From the second dose of IO-108 until the last treatment which is up to 2 years from the first treatment date
measure: Immunogenicity of IO-108 and IO-108+pembrolizumab
timeFrame: From the first dose until 30 days after the last treatment
measure: Anti-tumor activity of IO-108 and IO-108+pembrolizumab
timeFrame: 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
measure: Determine disease control rates of IO-108 as monotherapy or in combination with either pembrolizumab or cemiplimab
timeFrame: 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:
measure: Receptor occupancy of IO-108 in IO-108 monotherapy and IO-108+pembrolizumab
timeFrame: From the first dose of IO-108 till 21 days after
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC-HOPE (140) (USOR SITE)
state: Arizona
city: Beverly Hills
country: United States
facility: Beverly HIlls Cancer Center (129)
state: California
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers, LLP (141) (USOR SITE)
state: Colorado
city: Gainesville
country: United States
facility: University of Florida (125)
state: Florida
city: Lake Mary
country: United States
facility: Florida Cancer Specialists (134)
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute (146)
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists & Research Institute (103)
state: Florida
city: Stuart
country: United States
facility: Hematology Oncology (136)
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Comprehensive Cancer Center (123)
state: Indiana
city: Columbia
country: United States
facility: Maryland Oncology Hematology, PA (145) (USOR SITE)
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute (126)
state: Michigan
city: Billings
country: United States
facility: St. Vincent - Frontier Cancer Center (135)
state: Montana
city: New York
country: United States
facility: NYU Langone Health (131)
state: New York
city: Huntsville
country: United States
facility: Carolina BioOncology (102)
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center (128)
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Clinical Trials, LLC (144) (USOR SITE)
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Institute (104)
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center (105)
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology - Austin (142) (USOR SITE)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. (143) (USOR SITE)
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center (101)
state: Texas
city: Houston
country: United States
facility: Oncology Consultants, P.A. (138)
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology-Virginia (121)
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute (147)
state: Washington
Study officials:
affiliation: Immune-Onc Therapeutics
name: Wen Hong Lin, MD
role: STUDY_DIRECTOR
References: