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

Solid Tumor, Adult Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05054348
• Other study ID #: IO-108-CL-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 30, 2021
• Est. completion date: April 26, 2024

Study information

• Verified date: March 2024
• Source: Immune-Onc Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 309
• Est. completion date: April 26, 2024
• Est. primary completion date: March 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

Biological:
• IO-108
IO-108 given as monotherapy
• IO-108 + pembrolizumab combination therapy
IO-108 and fixed dose pembrolizumab combination therapy
• IO-108 + cemiplimab combination therapy
IO-108 and fixed dose cemiplimab combination therapy

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Immune-Onc Therapeutics	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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