Clinical trial NCT05678270: A Study of ICP-192 in Patients With FGFR2-Rearranged Unresectable or Metastatic Intrahepatic Cholangiocarcinoma
Official title: A Single-Arm, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of ICP-192 in Subjects With Unresectable or Metastatic Intrahepatic Cholangiocarcinoma With FGFR2 Fusions/Rearrangements Who Have Failed Prior Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Intrahepatic Cholangiocarcinoma (ICC)
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-01-10
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. The purpose of this study is to evaluate the efficacy and safety in patients with FGFR2-Rearranged unresectable or metastatic intrahepatic cholangiocarcinoma who failed prior therapy


Eligibility criteria: Inclusion Criteria:

1. Signed the ICF and Age ≥ 18 years old, either sex.
2. ECOG score of 0-1.
3. Life expectancy \> 3 months.
4. Histopathologically or cytopathologically confirmed intrahepatic cholangiocarcinoma with unresectable, recurrent or metastatic (AJCC 2017, 8th edition, TNM stage IV) tumor that has progressed following at least one line of chemotherapy and progression/recurrence within 6 months after neoadjuvant/adjuvant chemotherapy may be included.
5. FGFR2 fusion /rearrangement as confirmed by the central laboratory.
6. At least one measurable lesion at screening as target lesion per RECIST 1.1.
7. Organ functions meeting the protocol requirements.
8. Contraception according to the protocol requirements.

Exclusion Criteria:

1. Presence of other malignancies requiring medical intervention.
2. Prior treatment with selective FGFR inhibitors or FGFR antibodies.
3. Treatment with biological products, radical radiotherapy, and other investigational drugs within 4 weeks prior to the first dose of study drug. Chemotherapy within 3 weeks prior to the first dose of study drug.
4. Known symptomatic central nervous system (CNS) metastases.
5. Patients who have not recovered from the toxicity caused by previous anti-tumor treatment and have ≥ Grade 2 adverse events (judged per CTCAE V5.0 evaluation criterion) at the first dose of study drug.
6. Currently uncontrolled cardiovascular and cerebrovascular diseases, or a past medical history.
7. Any unstable or uncontrolled systemic disease as judged by the investigator, such as: active infection requiring intravenous therapy, uncontrolled hypertension (After treatment systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 90 mmHg), and diabetes mellitus (HbA1c \> 8%).
8. Current active bleeding, such as deep venous thrombosis, portal hypertension signs leading to gastroesophageal venous bleeding.
9. Wound with active infection.
10. Major surgical procedures within 4 weeks prior to the first dose of the study drug or minor surgical procedures within 2 weeks prior to the first dose of the study drug.
11. Any corneal or retinal abnormalities that may result in an increased risk of ocular toxicity
12. History and/or current evidence of extensive tissue calcification, including but not limited to calcification in soft tissues, kidney, intestine, myocardium, vasculature and/or the lungs, with the exception of lymph node calcification, mild pulmonary parenchymal calcification, and asymptomatic coronary artery calcification.
13. Clinically serious gastrointestinal dysfunction that may affect the intake, transport or absorption of the study drug (such as poorly controlled nausea, vomiting, diarrhea; malabsorption syndrome; intestinal obstruction and small bowel resection, etc.), or the patient was unable to swallow the drug orally.
14. Active HBV infection, Active HCV infection, HIV infection.
15. Female subjects who are pregnant or breastfeeding, or plan to have a pregnancy within 6 months after the last dose of the study drug; or male subjects who plan to father a child during the study or within 6 months after the last dose of the study drug.
16. The last dose of strong CYP3A inhibitor or CYP3A inducer (including food, western medicine, traditional Chinese medicine) is less than 5 half-lives before the first dose of study drug, or plans to take concomitant drugs or foods with strong CYP3A inhibition or induction during the study.
17. Known allergy to any excipients of the study drug.
18. Subjects with conditions that in the investigator's opinion are not suitable for participating in this trial.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 3 years
measure: Disease control rate (DCR)
timeFrame: Up to 3 years
measure: Duration of response (DOR)
timeFrame: Up to 3 years
measure: Time to response (TTR)
timeFrame: Up to 3 years
measure: Overall survival (OS)
timeFrame: Up to 3 years
measure: The adverse event (AE) of ICP-192 assessed by NCI-CTCAE V5.0
timeFrame: Up to 3 years
measure: Maximum concentration (Cmax)
timeFrame: Up to 3 years
measure: Time to maximum concentration (Tmax)
timeFrame: Up to 3 years
measure: Half-life (T1/2)
timeFrame: Up to 3 years
measure: Area under the concentration-time curve (AUC)
timeFrame: Up to 3 years
measure: Apparent clearance (CL/F)
timeFrame: Up to 3 years
measure: Terminal apparent volume of distribution (Vz/F)
timeFrame: Up to 3 years
Other outcomes:
measure: To explore the relationship between blood phosphorus and clinical efficacy
timeFrame: Up to 3 years
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Youan Hosptital,Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Fujian
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: FuZhou
country: China
facility: Mengchao hepatobiliary Hospital of FuJian Medical university
state: Fujian
city: Foshan
country: China
facility: Foshan First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: ZhuJiang Hospital of Southern Medical University
state: Guangdong
city: Shijiazhuang
country: China
facility: Hebei Medical University Fourth Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University.
state: Henan
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Human Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South Uninversity
state: Hunan
city: Changzhou
country: China
facility: Changzhou Tumor Hospital
state: Jiangsu
city: Jiangyin
country: China
facility: Jiangyin Renmin Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The Affiliated Hospital of Nanjing University Meidical School
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital&Institute
state: Liaoning
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Nanchang
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Xi'an
country: China
facility: Tangdu Hospital of the Fourth Military Medical University
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Affiliated Cancer Hospital of Shandong First Medical University
state: Shandong
city: Shanghai
country: China
facility: ZhongShan Hospital
state: Shanghai
city: Shanghai
country: China
facility: The Third Affiliated Hospital of Naval Medical University
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Shulan（Hangzhou） Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Shanghai East Hospital
name: Jin Li
role: PRINCIPAL_INVESTIGATOR
References: