Clinical trial NCT05309187: Dose-Escalation and Dose-Expansion Study of IO-202 and IO-202+Pembrolizumab in Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor, Adult
Keywords: IO-202
Lead sponsor: Immune-Onc Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-04-04
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-emergent and serious adverse events in patients treated with IO-202 and IO-202 + pembrolizumab
timeFrame: From first dose of IO-202 until the end of treatment which is up to 2 years from the first treatment date
measure: Dose-limiting toxicities (DLTs) with IO-202 and IO-202 + pembrolizumab
timeFrame: From the first dose of IO-202 and IO-202 + pembrolizumab until 21 days after 1st treatment
measure: Study discontinuations due to adverse events (AEs)
timeFrame: From the first dose of IO-202 IO-202 and IO-202 + pembrolizumab up to 2 years from the first treatment.
Secondary outcomes:
measure: Maximum serum concentration (Cmax) of IO-202
timeFrame: From the first dose of IO-202 until Cycle 5, Day 1
measure: Minimum concentration of IO-202
timeFrame: From the first dose of IO-202 until the last treatment which is up to 2 years from the first treatment date
measure: Immunogenicity of IO-202 and IO-202 + pembrolizumab
timeFrame: From the first dose until 24 months after the last treatment
measure: Anti-tumor activity of IO-202 and IO-202 + 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 an estimated period of 24 months
Other outcomes:
measure: Receptor occupancy in IO-202 monotherapy and IO-202 + pembrolizumab
timeFrame: From the first dose of IO-202 till 21 days after
Locations:
city: Los Angeles
country: United States
facility: USC-Norris Comprehensive Cancer Center (119)
state: California
city: Gainesville
country: United States
facility: University of Florida (125)
state: Florida
city: Chicago
country: United States
facility: Northwestern University - Feinberg School of Medicine (133)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University (123)
state: Indiana
city: New York
country: United States
facility: Tisch Mount Sinai (124)
state: New York
city: Huntsville
country: United States
facility: Carolina BioOncology (102)
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute/Tennessee Oncology (122)
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research (108)
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center (101)
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology Virginia (121)
state: Virginia
Study officials:
affiliation: Immune-Onc Therapeutics
name: Roya Nawabi, MBA
role: STUDY_DIRECTOR
References: