Study of Tinengotinib VS. Physician's Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma

Study Overview
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Brief Summary
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This study is a Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib versus Physician's Choice in Subjects with Fibroblast Growth Factor Receptor (FGFR)-altered, Chemotherapy- and FGFR Inhibitor-Refractory/Relapsed Cholangiocarcinoma

Detailed Description
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Approximately 200 subjects will be enrolled. Eligible subjects will be randomized in a 2:2:1 ratio to receive tinengotinib 8 mg QD, tinengotinib 10 mg QD or Physician's Choice in Part A; and eligible subjects will be randomized in a 2:1 ratio to receive the recommended Part B dose or selected dose or Physician's Choice in Part B.

Official Title
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A Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib VS Physician's Choice in Subjects With FGFR-altered, Chemotherapy- and FGFR Inhibitor-Cholangiocarcinoma

Conditions
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Cholangiocarcinoma

Intervention / Treatment
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* Drug: Tinengotinib 8 mg
* Drug: Tinengotinib 10 mg
* Drug: Physician's Choice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age at the time of signing the informed consent form (ICF). Histologically or cytologically confirmed CCA/adenocarcinoma of biliary origin with radiological evidence of unresectable or metastatic disease. Documentation of FGFR2 fusion/rearrangement gene status Subjects must have received at least one line of prior chemotherapy and exactly one FDA approved FGFR inhibitor. Exclusion Criteria: Prior receipt of two or more FGFR inhibitors, either approved or investigational drugs. Subjects with known brain or central nervous system (CNS) metastases that have radiologically or clinically progressed in the 28 days prior to initiation of therapy. Subjects with asymptomatic brain/CNS metastases or treated brain/CNS metastases that have been clinically stable for 14 days on steroids without escalation of steroids are eligible for enrollment. 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. 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. Concurrent anticancer therapy including chemo-, immune-, or radiotherapy. Hormone therapy may be allowed with Sponsor approval. 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. Subjects with uncontrolled hypertension (defined as blood pressure of ≥ 150 mm Hg systolic and/or ≥ 90 mm Hg diastolic despite adequate treatment with antihypertensive medications at screening)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tinengotinib 8 mg QD<br>Tinengotinib will be administered in 28-day cycles. | Drug: Tinengotinib 8 mg<br>* Subjects randomized to receive tinengotinib will receive a starting dose of either 8 mg QD., self-administered orally QD in 28-day cycles.<br>|
| Experimental: Tinengotinib 10 mg QD<br>Tinengotinib will be administered in 28-day cycles. | Drug: Tinengotinib 10 mg<br>* Subjects randomized to receive tinengotinib will receive a starting dose of either10 mg QD., self-administered orally QD in 28-day cycles.<br>|
| Active Comparator: Physician's Choice<br>Physician's Choice treatments include FOLFOX or FOLFIRI | Drug: Physician's Choice<br>* For subjects receiving FOLFOX or FOLFIRI, the subject will receive treatment every two weeks, with two administrations per each 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: 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 30 days from study discontinuation | 
| Part B: PFS by BICR | Progression-free survival (PFS) by BICR: PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or date of death due to any cause, whichever is earlier. | From first study drug administration until the date of first documented progression assessed by BICR or date of death from any cause, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: ORR by Investigator | ORR:objective response rate (ORR), 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. | 
| Part A: DOR by Investigator | Duration of response for CR or PR based on RECIST version 1.1. | Through study completion, an average of 9 months. | 
| Part B:Overall Survival (OS) | OS is defined as the time from date of randomization to date of death of any cause. | From first study drug administration until the date of death from any cause, assessed up to 24 months. | 
| Part B: Objective Response Rate (ORR) by BICR and 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 9 months. | 
| Part B: Duration of Response (DOR) by BICR and by Investigator | Duration of response for CR or PR based on RECIST version 1.1. | Through study completion, an average of 9 months. | 
| Part B: PFS by Investigators per RECIST v1.1. | PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory/Relapsed Cholangiocarcinoma