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

NCT04919642 | Completed Phase 2 FDA Drug

• 1 other identifier: TT420C1206
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 32

Brief 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.

Conditions

Cholangiocarcinoma; FGFR2 Fusion; FGFR2 Gene Mutation; FGFR1 Alteration; FGFR3 Alteration

Outcome Measures

Primary Outcomes (4)

• 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.

• 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.

• ORR in patients with FGFR alterations other than FGFR2 fusions (Cohort B)

  Through study completion, an average of 9 months.

• ORR in patients without FGFR alterations (wild-type FGFR mutation status) (Cohort C)

  Through study completion, an average of 9 months.

Secondary Outcomes (6)

• ORR in all patients with FGFR alterations (Cohorts A and B)

  Through study completion, an average of 9 months.

• 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

• Disease Control Rate (DCR) (All Cohorts)

  Through study completion, an average of 9 months.

• Overall Survival (OS) (All Cohorts)

  From first study drug administration until the date of death from any cause, assessed up to 24 months

• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment (All Cohorts)

  Up to 30 days from study discontinuation

Other Outcomes (1)

• Genetic Alteration Status

  Through study completion, an average of 9 months

Study Arms (4)

Cohort A1

EXPERIMENTAL

FGFR2 fusions who have failed at least one previous treatment with an FGFR inhibitor

Drug: TT-00420

Cohort A2

EXPERIMENTAL

FGFR2 fusions who have previously responded on at least one previous treatment with an FGFR inhibitor and discontinued due to disease progression

Drug: TT-00420

Cohort B

EXPERIMENTAL

Other FGFR alterations, including FGFR2 mutations and FGFR1/3 alterations, including fusions

Drug: TT-00420

Cohort C

EXPERIMENTAL

Negative for FGFR alterations (FGFR wild-type)

Drug: TT-00420

Interventions

TT-00420 DRUG

TT-00420 tablet, administered orally once daily

Cohort A1; Cohort A2; Cohort B; Cohort C

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age, at the time of signing informed consent
• 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)
• At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors5
• Documentation of FGFR gene alteration status
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• 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

You may not qualify if:

• Women who are pregnant or lactating
• Women of child-bearing potential (WOCBP) who do not use adequate birth control
• 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.
• 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.
• 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
• 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
• Patients with uncontrolled hypertension (defined as blood pressure of ≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic at Screening)
• Patients with:

Sponsors & Collaborators

• TransThera Sciences (Nanjing), Inc.: lead

Study Sites (32)

Providence Cancer Center

Anchorage, Alaska, 99508, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California, Los Angeles, School of Medicine

Santa Monica, California, 90404, United States

Location

USO Oncology Network- Rocky Mountain Cancer Centers

Denver, Colorado, 80218-1237, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

University of Chicago Medical Center - Duchossis Center for Advanced Medicine

Chicago, Illinois, 60637-1426, United States

Location

University of Maryland - Marlene and Stewart Greenebaum Cancer Center

Baltimore, Maryland, 21250, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health Center

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, 89169, United States

Location

Summit Medical Group - Florham Park Campus

Florham Park, New Jersey, 07932, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Ruttenberg Treatment Center - Mount Sinai

New York, New York, 10029, United States

Location

USOR Oncology Network- New York Oncology

New York, New York, 12208, United States

Location

Stony Brook University - Long Island Cancer Center

Stony Brook, New York, 11794, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

USO Oncology Network-Northwest Cancer Specialists, P.C.

Portland, Oregon, 97227, United States

Location

Medical College of South Carolina

Charleston, South Carolina, 29425, United States

Location

The University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Parkland Health & Hospital System

Dallas, Texas, 75235, United States

Location

University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, 75235, United States

Location

Houston Methodist Hospital - Outpatient Center

Houston, Texas, 77030, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

USO Oncology Network-Texas Oncology

Tyler, Texas, 75702-8363, United States

Location

USO Oncology Network-Virginia Oncology Associates - Brock Cancer Center - Norfolk

Norfolk, Virginia, 23502-2824, United States

Location

USO Oncology Network-Oncology and Hematology Associates of Southwest Virginia, Inc.

Roanoke, Virginia, 24014, United States

Location

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53705, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Javle M, Fountzilas C, Liao CY, Pelster M, Li D, Deming D, Sahai V, Fonkoua LK, Cohn A, Mantry P, Richards D, Kingsley E, Wu F, Peng P, Hennessy K, Wang H, Sun C, Ni S, Fan J, Mahipal A. Tinengotinib for adults with advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2026 Feb;11(2):137-149. doi: 10.1016/S2468-1253(25)00230-4. Epub 2025 Dec 2.

  PMID: 41349554 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Milind Javle, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 9, 2021
• Study Start: December 7, 2021
• Primary Completion: February 28, 2024
• Study Completion: February 28, 2024
• Last Updated: June 25, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (32)