Dose Confirmation and Dose Expansion Phase 1 Study of IO-108 and IO-108 + Anti-PD-1 in Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1 study to evaluate the safety, tolerability, PK, and preliminary efficacy of IO-108 monotherapy and in combination with anti-PD-1 monoclonal antibody pembrolizumab or tislelizumab in adult patients with advanced solid tumors. The study will be conducted in 3 parts, including Part A IO-108 monotherapy dose confirmation; Part B IO-108 + anti-PD-1 dose confirmation, and Part C dose expansion.

Official Title
-----------------
A Phase 1, Open-Label, Multicenter Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of IO-108 as Monotherapy and in Combination With Anti-PD-1 Monoclonal Antibody in Adult Patients With Advanced or Metastatic Solid Tumors

Conditions
-----------------
Advanced Solid Tumor

Intervention / Treatment
-----------------
* Biological: IO-108
* Biological: IO-108 + pembrolizumab
* Biological: IO-108 + tislelizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18, and < 75. Part A and Part B Cohort 1: Patients must have histologically or cytologically confirmed advanced or metastatic solid tumor and have failed, or have been intolerant for standard systemic therapy, or for whom no treatment known to confer clinical benefit exists. Part B Cohort 2 and Part C: Patient with advanced or metastatic solid tumor who meet the specific criteria. Patients have at least 1 measurable disease per RECIST v1.1 as assessed by local clinical site. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. Patients must have adequate hematologic function, hepatic function and renal function. Exclusion Criteria: Patients who previously received a monoclonal antibody therapy targeting LILRB2/ILT4 (including IO-108). Patients who received chemotherapy, radiotherapy, biologic therapy, targeted therapy, immunotherapy, or other investigational anti-cancer therapy < 4 weeks prior to their first day of study drug administration. Requires systemic corticosteroids at a dose of >10 mg daily of prednisone or the dose equivalent to other systemic corticosteroid, or other immunosuppressive agents ≤ 14 days prior to the first dose. History of radiation pneumonitis, non-infectious pneumonitis or interstitial lung disease expect for radioactive pulmonary fibrosis not requiring corticosteroid treatment. Symptomatic central nervous system (CNS) metastases. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: IO-108 monotherapy dose confirmation<br>Patients with advanced or metastatic solid tumors will be enrolled and treated with IO-108, intravenously, every 21 days. | Biological: IO-108<br>* IO-108, intravenously, on Day 1 of each 21-day cycle.<br>|
| Experimental: Part B: IO-108 + anti-PD-1 dose confirmation.<br>Patients will receive IO-108 in combination with with a fixed dose of pembrolizumab, intravenously, every 21 days; Patients will receive IO-108 in combination with with a fixed dose of tislelizumab, intravenously, every 21 days. | Biological: IO-108 + pembrolizumab<br>* IO-108, intravenously, on Day 1 of each 21-day cycle. Pembrolizumab will be administered intravenously on Day 1 of each 21-day cycle.<br>* Other names: IO-108 + Keytruda®;Biological: IO-108 + tislelizumab<br>* IO-108, intravenously, on Day 1 of each 21-day cycle. Tislelizumab will be administered intravenously on Day 1 of each 21-day cycle.<br>|
| Experimental: Part C: Dose expansion<br>Patients with advanced or metastatic solid tumors who meet the specific criteria will be enrolled into one of the cohorts. | Biological: IO-108 + pembrolizumab<br>* IO-108, intravenously, on Day 1 of each 21-day cycle. Pembrolizumab will be administered intravenously on Day 1 of each 21-day cycle.<br>* Other names: IO-108 + Keytruda®;Biological: IO-108 + tislelizumab<br>* IO-108, intravenously, on Day 1 of each 21-day cycle. Tislelizumab will be administered intravenously on Day 1 of each 21-day cycle.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) in patients treated with IO-108 | AE severity graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 | through study completion, an average of 2 years | 
| Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) in patients treated with IO-108 in combination with pembrolizumab or tislelizumab | AE severity graded by NCI CTCAE, Version 5.0 | through study completion, an average of 2 years | 
| Preliminary anti-tumor activity of IO-108 in combination with pembrolizumab or tislelizumab | ORR is defined as the percentage of patients who have a complete response (CR) or a partial response (PR) per RECIST v1.1 | through study completion, an average of 2 years | 

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 | through study completion, an average of 2 years | 
| Steady state concentration of IO-108 | Characterize steady state concentration of IO-108 by successive sampling of blood at pre-specified time points | through study completion, an average of 2 years | 
| Anti-drug antibodies (ADA) of IO-108 | Determine the incidence and titer of ADAs against IO-108 | through study completion, an average of 2 years | 
| Preliminary anti-tumor activity | Disease Control Rate, defined as the percentage of patients with CR, PR, or stable disease. | through study completion, an average of 2 years | 
| Preliminary anti-tumor activity | Progression-free Survival, defined as the time interval from the first dose date to the occurrence of disease progression or death of any cause | through study completion, an average of 2 years |