Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) in Cholangiocarcinoma

Cholangiocarcinoma Clinical Trial

Official title:

A Phase II, Open Label, Multicenter Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) Tablet in Adult Patients With Advanced Cholangiocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04919642
• Other study ID #: TT420C1206
• Status: Completed
• Phase: Phase 2
• Start date: December 7, 2021
• Est. completion date: February 28, 2024

Study information

• Verified date: December 2023
• Source: TransThera Sciences (Nanjing), Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is an open-label, multicenter study to evaluate the efficacy and safety of TT-00420 tablet in adult patients with advanced cholangiocarcinoma.

Description:

This is a Phase II, open-label study to evaluate the efficacy and safety of TT00420 in patients with advanced/metastatic and surgically unresectable cholangiocarcinoma (CCA) with 1) FGFR 2 fusions who failed prior FGFR inhibitor treatment, 2) FGFR2 fusions who responded on prior FGFR inhibitor treatment, 3) with other FGFR alterations, or 4) whose tumors do not contain a detectable FGFR alteration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: February 28, 2024
• Est. primary completion date: February 28, 2024
• 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 informed consent

2. Histologically or cytologically documented advanced/metastatic or surgically unresectable cholangiocarcinoma who have received at least one line of prior systemic chemotherapy. Patients will be assigned to 1 of 4 cohorts:

• Cohort A1: FGFR2 fusions who have failed at least one previous treatment with an FGFR inhibitor

• Cohort A2: FGFR2 fusions who have previously responded on at least one previous treatment with an FGFR inhibitor

• Cohort B: other FGFR alterations, including FGFR2 mutations and FGFR1/3 alterations, including fusions

• Cohort C: negative for FGFR alterations (FGFR wild-type)

3. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors5

4. Documentation of FGFR gene alteration status

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

6. Adequate organ function confirmed at screening and within 10 days of initiating treatment, as evidenced by:

• Absolute neutrophil count (ANC) = 1.5 x 10^9/L

• Hemoglobin (Hgb) = 8 g/dl

• Platelets (plt) = 75 x 10^9/L

• aspartate aminotransferase/serum glutamate oxaloacetate transaminase (AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) = 2.5 x Upper Limit of Normal (ULN) or = 5.0 x ULN if liver metastases are present

• Total bilirubin = 1.5 x ULN

• Calculated creatine clearance = 50 mL/min (Cockcroft Gault formula

7. Negative pregnancy test within 72 hours before starting study treatment in all premenopausal women and women < 12 months after the onset of menopause

8. Must agree to take sufficient contraceptive methods to avoid pregnancy (including male and female participants) during the study and until at least 6 months after ceasing study treatment

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

Exclusion Criteria:

1. Women who are pregnant or lactating

2. Women of child-bearing potential (WOCBP) who do not use adequate birth control

3. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g. evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases) Note: Patients with treated brain metastases that are off corticosteroids and have been clinically stable for 28 days are eligible for enrollment.

4. Patients 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 that has previously undergone potentially curative therapy.

5. Patients with the following mood disorders as judged by the Investigator or a psychiatrist:

• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)

• = CTCAE grade 3 anxiety

6. Impaired cardiac function or significant diseases, including but not limited to any of the following:

• left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)

• Congenital long QT syndrome

• QTcF = 480 msec on screening ECG

• Unstable angina pectoris = 3 months prior to starting study drug

• Acute myocardial infarction = 3 months prior to starting study drug

7. Patients with uncontrolled hypertension (defined as blood pressure of = 150 mmHg systolic and/or = 90 mmHg diastolic at Screening)

8. Patients with:

• unresolved diarrhea = CTCAE grade 2, or

• impairment of gastrointestinal (GI) function, or

• GI disease that may significantly alter the absorption of TT-00420.

9. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. uncontrolled hypertriglyceridemia [triglycerides > 500 mg/dL], or active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol

10. Patients who have received chemotherapy, targeted therapy, or immunotherapy = 5 half-lives or 3 weeks, whichever is shorter, (6 weeks for nitrosourea or mitomycin-C) prior to starting study drug

11. Patients who have received wide field radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to starting study drug or who have not recovered from adverse events of prior therapy

12. Patients who have undergone major surgery = 4 weeks prior to starting study drug or who have not recovered from adverse events of prior therapy

13. Patients who are currently receiving treatment with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants

14. Patients who are currently receiving treatment with strong CYP3A inhibitors or inducers, or sensitive substrates of CYP3A4 = 2 weeks prior to starting study drug.

15. Patients who are using a proton pump inhibitor within 4 days prior to the start of study therapy or a histamine-2 blocker within 2 days prior to the start of study therapy.

16. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory; patients with well controlled HIV might be enrolled per investigator's discretion and Sponsor approval)

17. Evidence of active infection with Hepatitis B or Hepatitis C that is not adequately controlled. For patients with known prior history of Hepatitis B or Hepatitis C, enrollment may be allowed per investigator's discretion and Sponsor approval.

18. Inability to swallow or tolerate oral medication

19. Has a history or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• FGFR2 Gene Mutation

Intervention

Drug:
• TT-00420
TT-00420 tablet, administered orally once daily

Locations

Country	Name	City	State
United States	Providence Cancer Center	Anchorage	Alaska
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Medical College of South Carolina	Charleston	South Carolina
United States	University of Chicago Medical Center - Duchossis Center for Advanced Medicine	Chicago	Illinois
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	University Hospitals Seidman Cancer Center	Cleveland	Ohio
United States	Methodist Dallas Medical Center	Dallas	Texas
United States	Parkland Health & Hospital System	Dallas	Texas
United States	University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center	Dallas	Texas
United States	USO Oncology Network- Rocky Mountain Cancer Centers	Denver	Colorado
United States	Henry Ford Health Center	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Summit Medical Group - Florham Park Campus	Florham Park	New Jersey
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	The University of Tennessee Medical Center	Knoxville	Tennessee
United States	Comprehensive Cancer Center of Nevada	Las Vegas	Nevada
United States	University of Wisconsin School of Medicine and Public Health	Madison	Wisconsin
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	USO Oncology Network-Virginia Oncology Associates - Brock Cancer Center - Norfolk	Norfolk	Virginia
United States	USO Oncology Network-Northwest Cancer Specialists, P.C.	Portland	Oregon
United States	USO Oncology Network-Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, Los Angeles, School of Medicine	Santa Monica	California
United States	Stony Brook University - Long Island Cancer Center	Stony Brook	New York
United States	USO Oncology Network-Texas Oncology	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
TransThera Sciences (Nanjing), Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Genetic Alteration Status	Evaluation of biomarkers, including but not limited to, FGFR mutation status	Through study completion, an average of 9 months
Primary	Objective Response Rate (ORR) in patients with FGFR2 fusions who have failed at least one previous treatment with an FGFR inhibitor (Cohort A1)	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 9 months.
Primary	ORR in patients with FGFR2 fusions who have responded (CR or PR) on at least one previous treatment with an FGFR inhibitor and discontinued due to progressive disease (Cohort A2)		Through study completion, an average of 9 months.
Primary	ORR in patients with FGFR alterations other than FGFR2 fusions (Cohort B)		Through study completion, an average of 9 months.
Primary	ORR in patients without FGFR alterations (wild-type FGFR mutation status) (Cohort C)		Through study completion, an average of 9 months.
Secondary	ORR in all patients with FGFR alterations (Cohorts A and B)		Through study completion, an average of 9 months.
Secondary	Progression Free Survival (PFS) (All Cohorts)		From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary	Disease Control Rate (DCR) (All Cohorts)	Defined as CR + PR + stable disease (SD)	Through study completion, an average of 9 months.
Secondary	Overall Survival (OS) (All Cohorts)		From first study drug administration until the date of death from any cause, assessed up to 24 months
Secondary	Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment (All Cohorts)	As assessed per CTCAE version 5.0	Up to 30 days from study discontinuation
Secondary	Concentration of TT-00420 at Protocol-Specified Timepoints (All Cohorts)		From Cycle 1 to Cycle 4, an average of 4 months (each cycle is 28 days)