Study of TT-00420 (Tinengotinib) in Subjects With Cholangiocarcinoma Who Failed or Relapsed to Chemotherapy and FGFR Inhibitor

Cholangiocarcinoma Metastatic Clinical Trial

Official title:

A Phase II, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Oral TT-00420 (Tinengotinib) Tablets in Subjects With Cholangiocarcinoma Who Failed or Relapsed to Prior Treatment of Chemotherapy and FGFR Inhibitor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06057571
• Other study ID #: TT00420CN08
• Status: Recruiting
• Phase: Phase 2
• Start date: November 17, 2023
• Est. completion date: October 31, 2025

Study information

• Verified date: December 2023
• Source: TransThera Sciences (Nanjing), Inc.
• Contact: Caixia Sun, PhD
• Phone: 025-58216298
• Email: sun_caixia[@]transtherabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase II, open-label, multicenter study to evaluate the efficacy and safety of oral TT-00420 (Tinengotinib) tablets in subjects with cholangiocarcinoma who failed or relapsed to prior treatment of chemotherapy and FGFR Inhibitor.

Description:

Approximately 50 subjects will be enrolled. Eligible subjects will receive tinengotinib 10 mg QD orally as the initial dose level in 21-day cycles until confirmed disease progression, intolerable toxicity, death, or withdrawal of consent.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: October 31, 2025
• Est. primary completion date: June 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. = 18 years of age at the time of signing the informed consent form (ICF).

2. Histologically or cytologically confirmed CCA/adenocarcinoma of biliary origin with radiological evidence of unresectable or metastatic disease.

3. Subjects must have received one or two lines of prior systemic chemotherapy.

4. Documentation of FGFR2 gene alteration and must have failed to prior treatment of exactly one FGFR inhibitor.

5. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors.

6. ECOG= 1.

7. Adequate organ and bone marrow function(without receiving any hematopoietic growth factor, blood or platelet therapy within 14 days before the first dose).

8. Must agree to take sufficient contraceptive methods to avoid pregnancy during the study and until at least 3 months after ceasing study treatment.

9. Able to sign informed consent and comply with the protocol.

Exclusion Criteria:

1. Subjects with concomitant brain or central nervous system (CNS) metastases and imaging or clinically confirmed progression within 28 days prior to the start of treatment. Brain or central nervous system metastases that not treated with corticosteroids and remain stable within 14 days prior to screening are eligible for enrollment.

2. Subjects with a known concurrent malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, including those that have previously undergone potentially curative therapy.

3. Subjects who have received prior systemic therapy or investigational study drug = 5 half-lives or 14 days, whichever is shorter, prior to starting the study drug or who have not recovered (grade = 1 or at pretreatment baseline except tolerable grade 2 alopecia, fatigue/asthenia, and neuropathy due to trauma) from adverse events (AEs) of prior therapy.

4. Concurrent anticancer therapy including chemo-, immune-, or radiotherapy. Hormone therapy may be allowed with Sponsor approval.

5. Subjects who have received wide field radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to starting the study drug or who have not recovered from AEs of prior therapy.

6. Subjects who have underwent major surgery or have not recovered from adverse events of surgery within the 4 weeks prior to initiation of the investigational drug (grade = 1 or at pretreatment baseline except tolerable grade 2 alopecia, fatigue/asthenia, and neuropathy due to trauma).

7. Impaired cardiac function or significant diseases.

8. Subjects who have received stable doses of antihypertensive drugs for at least 1 week with uncontrolled hypertension under at screening period (defined as blood pressure of = 150 mm Hg systolic and/or = 90 mm Hg diastolic despite adequate treatment with antihypertensive medications at screening).

9. Subjects who have severe gastrointestinal disease or gastrointestinal dysfunction that may lead to absorption, metabolism or excretion of the study drug, enrollment eligibility will be based on the investigator's judgment (including but not limited to total gastrotomy, short bowel syndrome).

10. Subjects who have bleeding disorders or thrombotic disorders or therapeutic anticoagulant therapy requiring INR monitoring.

11. Subjects who have received a strong CYP3A inhibitor and inducer before starting the study drug, within an interval of = 2 weeks or 5 half-lives (whichever is shorter); (except topical ketoconazole).

12. Tested positive for the human immunodeficiency virus (HIV).

13. Subjects who have an active HBV infection.

14. Subjects who are pregnant or breastfeeding.

15. Subjects who are unable to swallow or tolerate oral medication.

16. The investigator determines that he or she is not eligible for study participation for any clinical or laboratory abnormalities, or any reason that could confuse the study results, interfere with participants' safe participation and compliance with the trial procedure.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Cholangiocarcinoma Metastatic

Intervention

Drug:
• TT-00420 (tinengotinib)
TT-00420 (tinengotinib) tablet will be administered orally once daily per protocol defined schedule.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Beijing Cancer Hospital	Beijing
China	Beijing Tsinghua Changgeng Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Cancer Hospital	Changsha	Hunan
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	Sichuan Cancer Hospital	Chengdu	Sichuan
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	Central Hospital Affiliated to Shangdong First Medical University	Jinan	Shandong
China	Shandong Cancer Hospital	Jinan	Shandong
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Eastern Hepatobiliary Surgery Hospital	Shanghai	Shanghai
China	Fudan University Shanghai Cancer Hospital	Shanghai
China	Zhongshan Hospital	Shanghai
China	Liaoning Cancer Hospital	Shenyang	Liaoning
China	Shenzhen Qianhai Shekou Free Trade Zone hospital	Shenzhen	Guangdong
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Shanxi Cancer Hospital	Taiyuan	Shanxi
China	Tianjin medical university cancer institute & hospital	Tianjin
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Zhongnan hospital of Wuhan University	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
TransThera Sciences (Nanjing), Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) by BICR	The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.	Through study completion, an average of 1 year
Secondary	Progression-free survival (PFS)	From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first	Through study completion, an average of 1 year
Secondary	Overall Survival (OS)	From first study drug administration until the date of death from any cause	Through study completion, an average of 1 year
Secondary	ORR by Investigator	The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.	Through study completion, an average of 1 year
Secondary	Disease control rate (DCR)	The proportion of subjects who achieved a complete response (CR) or a partial response (PR) or a stable disease (SD) based on RECIST version 1.1.	Through study completion, an average of 1 year
Secondary	Duration of response (DOR)	Duration of response for CR or PR based on RECIST version 1.1.	Through study completion, an average of 1 year
Secondary	Incidence, duration, and severity of adverse events (AEs)	As assessed per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (or the most current version).	Up to 28 days from study discontinuation