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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Biological: IO-108; Biological: IO-108 + pembrolizumab; Biological: IO-108 + tislelizumab

• Study Type: Interventional
• Enrollment (Estimated): 89
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Rita Chen; Phone Number: 00862180168666; Email: rita.chen@immnueonc.com
• Study Contact Backup: Name: Ningbo Wang; Phone Number: 00862180168666; Email: ningbo.wang@immuneonc.com

Study Locations

• China
  • Fuzhou
    • Fujian, Fuzhou, China
      • Recruiting
      • The First Affiliated Hospital Of Fujian Medical University
      • Contact: Hong
  • Hainan
    • Haikou, Hainan, China
      • Recruiting
      • 1st affiliated Hospital of Hainan Medical University
      • Contact: Wu
  • Hebei
    • Shijia Zhuang, Hebei, China
      • Recruiting
      • 4th Hospitla of Hebei Medical University
      • Contact: YIN
      • Principal Investigator: Wang
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Recruiting
      • Harbin Cancer Hospital
      • Contact: Zhang
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Wang
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Tongji Hospital
      • Contact: Hu
  • Hunan
    • Changsha, Hunan, China, 410031
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Gu
  • Jiangxi
    • Nanchang, Jiangxi, China, 330052
      • Recruiting
      • The First Affiliated Hospital Of Nanchang University
      • Contact: Li
      • Contact: Wen
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • Liaoning cancer hospital
      • Contact: Zhang
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital
      • Contact: Sun
    • Linyi, Shandong, China
      • Recruiting
      • Lin Yi Cancer Hospital
      • Contact: SHI
  • Shanghai
    • Shanghai, Shanghai, China, 200120
      • Recruiting
      • Shanghai Dong Fang Hospital
      • Contact: Li
      • Contact: Guo
  • Shanxi
    • Xian, Shanxi, China
      • Recruiting
      • 1st Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Li
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Sir Run Run Shaw Hospital
      • Contact: PAN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18, and < 75.

2. 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.

3. Patients have at least 1 measurable disease per RECIST v1.1 as assessed by local clinical site.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
5. Patients must have adequate hematologic function, hepatic function and renal function.

Exclusion Criteria:

1. Patients who previously received a monoclonal antibody therapy targeting LILRB2/ILT4 (including IO-108).
2. 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.
3. 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.
4. History of radiation pneumonitis, non-infectious pneumonitis or interstitial lung disease expect for radioactive pulmonary fibrosis not requiring corticosteroid treatment.
5. Symptomatic central nervous system (CNS) metastases. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

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
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
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

Collaborators and Investigators

• Sponsor: Immune-Onc Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2022
• Primary Completion (Estimated): May 30, 2024
• Study Completion (Estimated): May 30, 2024

Study Registration Dates

• First Submitted: August 12, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (Actual): August 19, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Tislelizumab
• Other Study ID Numbers: IO-108-CL-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No