Clinical Study of ICP-192 in Solid Tumors Patients

NCT03758664 | Unknown Phase 1

• 1 other identifier: ICP-CL-00301
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 7

Brief Summary

Open-label, non-randomized, Phase I/IIa, dose-escalating, dose-extension, first-in-man study.

Conditions

Solid Tumor

Keywords

FGFR gene abnormalities

Outcome Measures

Primary Outcomes (2)

• Adverse events(Phase 1 dose escalation)

  Adverse events graded by CTCAE V5.0 as a measurement of the safety and tolerability profile of ICP-192

  From the time a signed and dated ICF until 28 days after last dose of study drug

• Objective Response Rate(ORR)(Phase 2a dose expansion)

  Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST).

  At the end of Cycle 4(each cycle is 21 days)

Secondary Outcomes (9)

• Cmax

  At the end of Cycle 1(each cycle is 21 days)

• AUC

  At the end of Cycle 1(each cycle is 21 days)

• Apparent half-life for designated elimination phases (t½)

  At the end of Cycle 1(each cycle is 21 days)

• Food effect

  Day 1 - 6 after single dose

• Objective Response Rate(ORR) (Phase 1 dose escalation)

  At the end of Cycle 4(each cycle is 21 days)

Study Arms (1)

ICP-192

EXPERIMENTAL

The initial dose of ICP-192 is 2 mg, QD, and dose escalation schedule may be modified based on the safety and PK from the previous dose. Tentatively seven dose levels will be evaluated.

Drug: ICP-192

Interventions

ICP-192 DRUG

Drug: ICP-192 Dose levels will be escalated following accelerated titration and modified "3+3" dose escalation scheme,

ICP-192

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An unresectable or metastatic advanced malignant solid tumor confirmed by histopathology that has failed to respond to known treatment or has recurred;Subjects who progress under standard treatment, are intolerant to standard treatment, or do not have standard treatment (dose escalation phase)
• Tissue or cell pathology confirmed unresectable, recurrent or metastatic (AJCC version 8 TNM staging IV (2017), biliary tract malignant tumor, or intolerance to first-line chemotherapy failure (twice (defined as reduction still cannot tolerate) first-line chemotherapy, neoadjuvant/progress/adjuvant chemotherapy after 6 months recurrence can be selected (dose extension stage); - At least one evaluable disease according to RECIST1.1
• FGFR2 translocation/fusion has been reported or FGFR2 translocation/fusion has been detected in central laboratory (dose extension phase);
• Age ≥18 and ≤75
• There is at least one evaluable lesion according to RECIST1.1 criteria
• ECOG strength score is 0-1 (dose escalation stage), and ECOG strength score is 0-2 (dose expansion stage).
• The expected survival time is more than 3 months
• The organ function level must meet the following requirements (subject to the upper limit of normal value in the clinical trial center):
• A) bone marrow: absolute count of neutrophils (ANC)≥1.5\*109/L (1500/mm3), platelet ≥75\*109/L, hemoglobin ≥9g/dL; B) coagulation function: international standardized ratio of prothrombin time and partial thrombin time \<1.5 times the upper limit of normal value; C) liver: serum bilirubin ≤1.5 times the upper limit of normal value (tumor involvement in the liver ≤2.5 times the upper limit of normal value), aspartic aminotransferase (AST) and alanine aminotransferase (ALT)≤3 times the upper limit of normal value (AST and ALT≤5 times the upper limit of normal value in the case of liver metastasis); D) serum creatinine ≤1.5 times the upper limit of normal value, or creatinine clearance ≥70mL/min (calculated according to the Cockroft-gult formula).
• Volunteer to enroll and sign informed consent to follow the treatment protocol and visit plan.

You may not qualify if:

• Previous treatment with FGFR small molecule inhibitors or antibody drugs.
• Anti-cancer therapy, such as chemotherapy (except for oral fluorouracil), immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks of the first dose of ICP-192, oral fluorouracil agents within two weeks of the first dose of ICP-192.
• Major surgery within 6 weeks of the first dose of ICP-192.
• Blood phosphate persistently above ULN with intervene therapy within two weeks of the first dose of ICP-192.
• Significant GI disorder(s) that could interfere with the absorption, metabolism, or excretion of ICP-192.
• Central nervous system (CNS) metastasis
• Current clinically significant cardiovascular disease including:
• Any class 3 or 4 cardiac disease such as arrhythmia, congestive heart failure or myocardial infarction defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) \< 50%, Primary cardiomyopathy, clinical significant QTc prolong history or QTc\>470ms (female) QTc\>450ms (male)
• Known active bleeding within 2 months of screening or 6 months of bleeding history.
• According to the investigator's judgement, there are evidences of a serious or uncontrollable systemic disease (such as unstable or uncompensated respiratory, liver or kidney disease); or any unstable systemic disease (including active clinically serious infections, uncontrolled hypertension, liver and kidney or metabolic diseases)
• History of interstitial pneumonia, deep vein thrombosis, pulmonary embolism. Stroke or intracranial hemorrhage within 6 months before the first dose of ICP-192.
• History of organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Any corneal or retinal abnormalities that may increase ocular toxicity, including but not limited to:
• History of central serous retinopathy (CSR) or retinal vein occlusion (RVO) disease or has related diseases;
• Active age-related macular degeneration (AMD);

Sponsors & Collaborators

• Beijing InnoCare Pharma Tech Co., Ltd.: lead

Study Sites (7)

ZhuJiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510000, China

NOT YET RECRUITING

Henan cancer hospital & Affiliated Tumor Hospital of Zhengzhou University

Zhengzhou, Henan, 450008, China

NOT YET RECRUITING

Hunan cancer hospital & the affiliated cancer hospital of xiangya school of medicine ,central south university

Changsha, Hunan, 410006, China

NOT YET RECRUITING

The Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215004, China

NOT YET RECRUITING

The First Bethune Hospital of Jilin University

Changchun, Jilin, 130021, China

NOT YET RECRUITING

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

RECRUITING

Cancer hospital of the university of Chinese academy of sciences

Hangzhou, Zhejiang, 310022, China

NOT YET RECRUITING

Study Officials

• Jin Li, PhD

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Li, PhD

CONTACT

8621-38804518; lijin@csco.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2018
• First Posted: November 29, 2018
• Study Start: December 19, 2018
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: July 6, 2022

Record last verified: 2022-06

Locations

CN (7)