A Study of ICP-192 in Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is a multi-center, open-label, phase I/II clinical study to evaluate ICP-192 in patients with advanced solid tumors and FGFR gene alterations. It consists of two parts: Part I (Phase I), dose escalation and Part II (Phase II), dose expansion.

Detailed Description
-----------------
Part I (Phase I) of the study enrolls patients with advanced solid tumors (9-15 patients); Part II (Phase II) of the study enrolls patients with urothelial carcinoma or cholangiocarcinoma with FGFR genetic alterations (30 patients).

Official Title
-----------------
A Multi-center Open-label, Phase I/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ICP-192 in Patients With Advanced Solid Tumors and FGFR Gene Alterations

Conditions
-----------------
Advanced Solid Tumors, Urothelial Carcinoma, Cholangiocarcinoma

Intervention / Treatment
-----------------
* Drug: Drug ICP-192


Participation Criteria
=================
Eligibility Criteria
-----------------
Major Inclusion Criteria Participants are eligible to be included in the study only if all of the following criteria apply: Participate voluntarily, sign informed consent, and follow the study treatment plan and scheduled visits; Phase I: Patients with histologically or cytologically confirmed unresectable or metastatic advanced malignant solid tumors who have progressed under standard treatment or recurred after or were intolerant to all standard treatment regimens, or have no standard treatment available; Phase II: patients with histologically or cytologically confirmed unresectable or metastatic urothelial carcinoma or cholangiocarcinoma, who have progressed or recurred after or were intolerant to first-line chemotherapy, or have progressed/relapsed within 12 months after neoadjuvant /adjuvant chemotherapy; Phase II: Existing test reports have confirmed the FGFR gene alteration or the central laboratory has detected the FGFR gene alteration. Age ≥18 years old; At least one measurable lesion according to the Response Evaluation Criteria of Solid Tumor, version 1.1 (RECIST 1.1); ECOG performance status of 0-1; Life expectancy for more than 3 months; Must have adequate organ function Major Exclusion Criteria Participants are excluded from the study if any of the following criteria apply: Have previously been treated with selective pan-FGFR molecular inhibitors or antibody drugs, except for the FGFR4 selective inhibitors; Within 2 weeks before the first dose of study drug, the subject's phosphate level continuing to exceed the ULN despite medical treatment; Patients with clinically significant gastrointestinal dysfunction Has known central nervous system metastases; Has a history of or currently uncontrolled cardiovascular diseases History of organ transplantation or a history of allogeneic hematopoietic stem cell transplantation; Current evidence of corneal or retinal abnormalities that may increase eye toxicity; Active hepatitis B virus active hepatitis C, or HIV infection; Has not recovered from reversible toxicity of prior anti-tumor therapy Pregnant or lactating women, as well as women with childbearing potential who are unwilling or unable to perform contraception from the screening to 6 months after the last study drug administration; and fertile men who are unwilling or unable to perform contraception from screening to 3months after the last study drug administration Other conditions considered by the investigator to be inappropriate for participation in this study. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICP-192<br>Dose Escalation Phase ICP-192 Dose Expansion Phase ICP-192 | Drug: Drug ICP-192<br>* Dose Escalation Phase ICP-192 will be taken by patients with advanced solid tumor and will be treated follow the 3+3 dose escalation scheme Dose Expansion Phase ICP-192 will be taken by patients with urothelial carcinoma or cholangiocarcinoma with FGFR gene alterations and will be treated at a single dose defined from the Dose Escalation Phase.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Phase I: Dose Escalation & Phase II: Dose Expansion To evaluate the safety and tolerability of different doses of ICP-192 in patients with advanced solid tumors | Up to 3 years | 
| MTD | Phase I: Dose Escalation To determine Maximum Tolerated Dose（MTD) for ICP-192 | Up to 3 years | 
| OBD | Phase I: Dose Escalation To determine Optimal Biological Dose (OBD) for ICP-192 | Up to 3 years | 
| RP2D | Phase I: Dose Escalation To determine Recommended Phase 2 Dose (RP2D) for ICP-192 | Up to 3 years | 
| ORR | Phase II: Dose Expansion Objective Response Rate | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak concentration (Cmax) | Phase I: Dose Escalation Peak concentration (Cmax) | Up to 3 years | 
| AUC | Phase I: Dose Escalation AUC | Up to 3 years | 
| DCR | Phase II: Dose Expansion disease control rate | Up to 3 years | 
| DOR | Phase II: Dose Expansion duration of response | Up to 3 years | 
| PFS | Phase II: Dose Expansion progression-free survival | Up to 3 years | 
| OS | Phase II: Dose Expansion overall survival | Up to 3 years |