A Study of ICP-189 and ICP-189 in Combination With Anti-PD-1 Monoclonal Antibody in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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A Dose finding Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Preliminary Anti-Tumor Activity of ICP-189 Tablets and ICP-189 Tablets in Combination with Anti-PD-1 Monoclonal Antibody in Patients with Advanced Solid Tumors.

Official Title
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A Phase Ia /Ib Dose Finding Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Preliminary Anti-Tumor Activity of ICP-189 and ICP-189 in Combination With Anti-PD-1 Monoclonal Antibody in Patients With Advanced Solid Tumors

Conditions
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Patients With Advanced Solid Tumors

Intervention / Treatment
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* Drug: ICP-189


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Patients with histologically confirmed locally advanced unresectable or metastatic solid tumors; At least one measurable lesion according to RECIST 1.1. Exclusion Criteria: Patients who have had other cancer(s) within 5 years prior to the first dose, except for locally curable cancers that have been apparently cured; Patients with unstable primary central nervous system (CNS) tumors or CNS metastases; Patients who have an active autoimmune disease or have had an autoimmune disease with risk of recurrence; Patients who have active or history of interstitial lung disease or non-infectious pneumonia; Patients who have a history of severe allergic reaction to any component of ICP-189 tablets or anti-PD-1 antibody (> grade 3 assessed by CTCAE 5.0). Other protocol-defined inclusion/exclusion criteria apply.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase Ia: ICP-189 Dose Escalation<br> | Drug: ICP-189<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of adverse event (AE) of ICP-189 assessed by NCI-CTCAE V5.0 | To assess the safety and tolerability of ICP-189 in patients with advanced solid tumors. | through study completion, an average of 2 years | 
| Dose-Limiting Toxicities (DLTs) | Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs). | through study completion, an average of 2 years | 
| Recommended Phase 2 Dose (RP2D) and/or maximum tolerated dose (MTD) | To preliminarily determine the PR2D and the MTD of ICP-189 in patients with advanced solid tumors | through study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum plasma concentration observed (Cmax) | To evaluate the pharmacokinetic (PK) characteristics of ICP-189 in patients with solid tumors. | through study completion, an average of 2 years | 
| Time of maximum observed plasma concentration (Tmax) | To evaluate the pharmacokinetic (PK) characteristics of ICP-189 in patients with solid tumors. | through study completion, an average of 2 years | 
| Elimination half-life (t1/2) | To evaluate the pharmacokinetic (PK) characteristics of ICP-189 in patients with solid tumors. | through study completion, an average of 2 years | 
| Area under plasma concentration-time curve (AUC0-t and AUC0-∞) | To evaluate the pharmacokinetic (PK) characteristics of ICP-189 in patients with solid tumors. | through study completion, an average of 2 years | 
| Apparent clearance (CL/F) | To evaluate the pharmacokinetic (PK) characteristics of ICP-189 in patients with solid tumors. | through study completion, an average of 2 years | 
| Apparent volume of distribution (Vz/F) | To evaluate the pharmacokinetic (PK) characteristics of ICP-189 in patients with solid tumors. | through study completion, an average of 2 years | 
| The objective response rate (ORR) | To evaluate the preliminary anti-tumor activity of ICP-189. | through study completion, an average of 2 years | 
| Duration of response (DoR) | To evaluate the preliminary anti-tumor activity of ICP-189. | through study completion, an average of 2 years | 
| Progression-free survival (PFS) | To evaluate the preliminary anti-tumor activity of ICP-189. | through study completion, an average of 2 years | 
| Overall survival (OS) | To evaluate the preliminary anti-tumor activity of ICP-189. | through study completion, an average of 3.5 years |