Efficacy and Safety of 3D185 Monotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is evaluate the efficacy of 3D185 in subjects with advanced/metastatic cholangiocarcinoma with FGFR2 Gene Alterations who have failed at least 1 previous treatment.

Official Title
-----------------
An Open-label, Single Arm, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of 3D185 Monotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma With FGFR2 Gene Alterations

Conditions
-----------------
Cholangiocarcinoma,Adult

Intervention / Treatment
-----------------
* Drug: 3D185


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed cholangiocarcinoma. Documented disease progression following at least one previous systemic cancer therapy Tumor assessment for FGF/FGFR gene alteration status. Have measurable disease according to RECIST v1.1 ECOG Performance Status ≤ 2 Life expectancy ≥ 12 weeks. Exclusion Criteria: Previously received selective FGFR inhibitor therapy. History of and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcifications. Have any of the following eye diseases/conditions: 1) history of retinal pigment epithelial detachment (RPED); 2) history of laser treatment or intraocular injection for macular degeneration; 3) history of dry or wet age-related macular degeneration; 4) history of retinal vein occlusion (RVO); 5) history of retinal degenerative diseases; 6) history of chorioretinal lesions.. Received CYP3A4 and/or CYP2C8 strong inhibitors or CYP3A4 strong inducers within 14 days prior to the first dose and subject who need to continue using these drugs.

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: All eligible subjects<br> | Drug: 3D185<br>* All eligible subjects will receive the RP2D regimen to be established based on the results of the ongoing phase I study from Cycle 1 Day 1 (C1D1) until disease progression, intolerable toxicity, withdrawal of consent, whichever occurs first.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | defined as the proportion of subjects who achieved a confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 as assessed by investigators. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DoR) | DoR is defined as the time from the date of first CR or PR based on RECIST v1.1 to the date of first documented progressive disease based on RECIST v1.1 or death, whichever occurs first. | 24 months | 
| Disease control rate (DCR) | defined as the proportion of subjects who achieve a confirmed complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST v1.1 as assessed by investigators. | 24 months | 
| Progression-free survival (PFS) | PFS is defined as the time from the date of first study dose to disease progression based on RECIST v1.1 or death, whichever occurs first. | 24 months | 
| Overall survival (OS) | OS is defined as the date of first study dose to the date of death from any cause. | 24 months | 
| 3D185 Plasma concentration | The pharmacokinetic and pharmacodynamics assessments will be analyzed descriptively and presented in appropriate tables or figures. | 24 months | 
| Serum phosphate levels | The pharmacokinetic and pharmacodynamics assessments will be analyzed descriptively and presented in appropriate tables or figures. | 24 months |