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A Study of TY-1091 in Patients With Advanced Solid Tumors

Primary Purpose

RET-altered Non Small Cell Lung Cancer, Medullary Thyroid Cancer, RET-altered Papillary Thyroid Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TY-1091
Sponsored by
TYK Medicines, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for RET-altered Non Small Cell Lung Cancer

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis during dose escalation (Phase 1) - Pathologically documented, definitively diagnosed non-resectable advanced solid tumor. All participants treated at doses > 50 mg per day must have MTC, or a RET-altered solid tumor per assessment of tumor tissue and/or blood In the expansion stage phase (Phase 2) , patients should fulfill the following criteria at Screening Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC, MTC, or other solid tumors. Subject must have a documented RET gene fusion or mutation by a CLIA certified or equivalent testing. Next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR) test or fluorescence in situ hybridization (FISH) can be used to determine molecular eligibility At least one measurable lesion as defined by RECIST 1.1, not previously irradiated and not chosen for biopsy during the screening period. Patients without RECIST 1.1 measurable disease will be eligible for enrollment in Cohort 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 with no sudden deterioration 2 weeks prior to the first dose of study treatment. Life expectancy of at least 3 months. Adequate organ functions. Ability to swallow capsules and willing and able to provide written informed consent approved by institutional review board (IRB) or independent ethics committee (IEC). Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and 6 months following the last dose of study treatment; this may include barrier methods such as condom or diaphragm with spermicidal gel. Exclusion Criteria: For NSCLC patients, a targetable mutation in EGFR or MET, targetable rearrangement involving ALK, ROS1 or NTRK1-3. History of other previous cancer (except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected), requiring therapy within the previous 5 years. For MTC patients, clinically significant involvement in the trachea, esophagus or complete encasement of great vessels (e.g., aorta or pulmonary artery) that in the opinion of the Investigator, could result in life-threatening complications due to rapid tumor regression. Symptomatic primary central nervous system (CNS) tumor or metastases; symptomatic leptomeningeal carcinomatosis; untreated spinal cord compression. Cardiovascular and cerebrovascular diseases/symptoms/indications meeting any of the following conditions: Mean resting corrected QT interval (electrocardiogram interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) ≥470 msec obtained from 3 electrocardiograms; Any clinically significant resting ECG abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, second and third degree heart block, PR interval > 250 ms; Any factors that increase the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in a first-degree relative under 40 years of age, or any concomitant medication known to prolong QT interval; Left ventricular ejection fraction (LVEF) < 50%; Patients with a previous history of decreased myocardial contractility who experienced relevant symptoms within 6 months prior to study drug administration: such as chronic congestive heart failure, pulmonary edema or decreased cardiac ejection fraction; Patients with a history of acute or chronic cardiovascular and cerebrovascular diseases who had relevant symptoms within 6 months prior to study drug administration: such as myocardial infarction, severe or unstable angina, cerebral infarction, cerebral hemorrhage or transient ischemic attack. Patients who have received treatment within 14 days prior to the first dose or need to continue treatment with strong CYP3A4 inducers/strong inhibitors, CYP3A4/CYP2C9/CYP2C19 sensitive substrate with a narrow treatment window or strong p-glycoprotein inhibitors. Systemic anti-tumor treatment such as standard chemotherapy, biological therapy and immunological drug therapy within 28 days prior to the first dose; targeted therapy within 14 days or 5 half-lives of the first dose (calculated as a long time); anti-tumor traditional Chinese traditional medicine treatment within 7 days prior to the first dose.

Sites / Locations

  • Jinlin Province Cancer Hosipital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phase 1 Dose Escalation

Phase 2 Dose Expansion

Arm Description

Multiple doses of TY-1091 for oral administration. Intervention: Drug: TY-1091

Multiple doses of TY-1091 for oral administration. Intervention: Drug: TY-1091

Outcomes

Primary Outcome Measures

(Phase 1 )Dose Limiting Toxicity (DLT)
(Phase 1) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
(Phase 2) Overall Response Rate (ORR)

Secondary Outcome Measures

(Phase 1) Overall Response Rate (ORR)
iORR
DCR
CBR
DOR
PFS
OS
(Phase 1 and 2) Pharmacokinetic Parameters Including Maximum Plasma Drug Concentration (Cmax)
(Phase 1 and 2) Pharmacokinetic Parameters Including Terminal Elimination Half-life (t1/2)
(Phase 1 ) AUC0-24
(Phase 1 and 2) Pharmacokinetic Parameters Including Tmax
(Phase 1 and 2) Pharmacokinetic Parameters Including Cmin
(Phase 1 ) AUC0-t
(Phase 1 ) AUCinf
(Phase 1 ) inflearance rate constant (Kel)
(Phase 1 ) apparent clearance (CL/F)
(Phase 1 ) Vd/F
(Phase 1 ) mean residence time (MRTinf)

Full Information

First Posted
December 9, 2022
Last Updated
December 21, 2022
Sponsor
TYK Medicines, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT05675605
Brief Title
A Study of TY-1091 in Patients With Advanced Solid Tumors
Official Title
A Phase I/II Study of Oral TY-1091 in Adult Patients With Advanced Solid Tumors, Including RET-Fusion Non-Small Cell Lung Cancer, RET-Mutation Medullary Thyroid Cancer, and Other Tumors With RET Alterations
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 1, 2023 (Anticipated)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TYK Medicines, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of TY-1091 administered orally in participants with medullary thyroid cancer (MTC), RET-altered NSCLC and other RET-altered solid tumors.
Detailed Description
The study consists of 2 parts, a dose-escalation part (Phase 1) and an expansion part (Phase 2). Part1 will enroll participants with advanced non-resectable NSCLC, advanced non-resectable thyroid cancer and other advanced solid tumors that have progressed following standard systemic therapy, have not adequately responded to standard systemic therapy, or the participants must be intolerant to or the Investigator has determined that treatment with standard therapy is not appropriate, or there must be no accepted standard therapy for their disease. A multicenter, open-label design is adopted for part2. According to the obtained data of safety, tolerability, PK characteristics, and preliminary efficacy of TY-1091, one or two doses will be selected to conduct a dose expansion trial, which includes 3 cohorts with 20-40 subjects in each cohort.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
RET-altered Non Small Cell Lung Cancer, Medullary Thyroid Cancer, RET-altered Papillary Thyroid Cancer, Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
248 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 Dose Escalation
Arm Type
Experimental
Arm Description
Multiple doses of TY-1091 for oral administration. Intervention: Drug: TY-1091
Arm Title
Phase 2 Dose Expansion
Arm Type
Experimental
Arm Description
Multiple doses of TY-1091 for oral administration. Intervention: Drug: TY-1091
Intervention Type
Drug
Intervention Name(s)
TY-1091
Intervention Description
TY-1091(10mg,100mg) , once a day, oral administration Dose level is from 20mg to 800mg
Primary Outcome Measure Information:
Title
(Phase 1 )Dose Limiting Toxicity (DLT)
Time Frame
First 25 days of dosing
Title
(Phase 1) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Approximately 12 months
Title
(Phase 2) Overall Response Rate (ORR)
Time Frame
up to 24 weeks
Secondary Outcome Measure Information:
Title
(Phase 1) Overall Response Rate (ORR)
Time Frame
up to 24 weeks
Title
iORR
Time Frame
up to 24 weeks
Title
DCR
Time Frame
up to 24 weeks
Title
CBR
Time Frame
1 year
Title
DOR
Time Frame
Approximately 1 year
Title
PFS
Time Frame
Up to approximately 33 months
Title
OS
Time Frame
Up to approximately 33 months
Title
(Phase 1 and 2) Pharmacokinetic Parameters Including Maximum Plasma Drug Concentration (Cmax)
Time Frame
First 46 days of dosing
Title
(Phase 1 and 2) Pharmacokinetic Parameters Including Terminal Elimination Half-life (t1/2)
Time Frame
First 46 days of dosing
Title
(Phase 1 ) AUC0-24
Time Frame
First 46 days of dosing
Title
(Phase 1 and 2) Pharmacokinetic Parameters Including Tmax
Time Frame
First 46 days of dosing
Title
(Phase 1 and 2) Pharmacokinetic Parameters Including Cmin
Time Frame
First 46 days of dosing
Title
(Phase 1 ) AUC0-t
Time Frame
First 46 days of dosing
Title
(Phase 1 ) AUCinf
Time Frame
First 46 days of dosing
Title
(Phase 1 ) inflearance rate constant (Kel)
Time Frame
First 46 days of dosing
Title
(Phase 1 ) apparent clearance (CL/F)
Time Frame
First 46 days of dosing
Title
(Phase 1 ) Vd/F
Time Frame
First 46 days of dosing
Title
(Phase 1 ) mean residence time (MRTinf)
Time Frame
First 46 days of dosing

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis during dose escalation (Phase 1) - Pathologically documented, definitively diagnosed non-resectable advanced solid tumor. All participants treated at doses > 50 mg per day must have MTC, or a RET-altered solid tumor per assessment of tumor tissue and/or blood In the expansion stage phase (Phase 2) , patients should fulfill the following criteria at Screening Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC, MTC, or other solid tumors. Subject must have a documented RET gene fusion or mutation by a CLIA certified or equivalent testing. Next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR) test or fluorescence in situ hybridization (FISH) can be used to determine molecular eligibility At least one measurable lesion as defined by RECIST 1.1, not previously irradiated and not chosen for biopsy during the screening period. Patients without RECIST 1.1 measurable disease will be eligible for enrollment in Cohort 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 with no sudden deterioration 2 weeks prior to the first dose of study treatment. Life expectancy of at least 3 months. Adequate organ functions. Ability to swallow capsules and willing and able to provide written informed consent approved by institutional review board (IRB) or independent ethics committee (IEC). Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and 6 months following the last dose of study treatment; this may include barrier methods such as condom or diaphragm with spermicidal gel. Exclusion Criteria: For NSCLC patients, a targetable mutation in EGFR or MET, targetable rearrangement involving ALK, ROS1 or NTRK1-3. History of other previous cancer (except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected), requiring therapy within the previous 5 years. For MTC patients, clinically significant involvement in the trachea, esophagus or complete encasement of great vessels (e.g., aorta or pulmonary artery) that in the opinion of the Investigator, could result in life-threatening complications due to rapid tumor regression. Symptomatic primary central nervous system (CNS) tumor or metastases; symptomatic leptomeningeal carcinomatosis; untreated spinal cord compression. Cardiovascular and cerebrovascular diseases/symptoms/indications meeting any of the following conditions: Mean resting corrected QT interval (electrocardiogram interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) ≥470 msec obtained from 3 electrocardiograms; Any clinically significant resting ECG abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, second and third degree heart block, PR interval > 250 ms; Any factors that increase the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in a first-degree relative under 40 years of age, or any concomitant medication known to prolong QT interval; Left ventricular ejection fraction (LVEF) < 50%; Patients with a previous history of decreased myocardial contractility who experienced relevant symptoms within 6 months prior to study drug administration: such as chronic congestive heart failure, pulmonary edema or decreased cardiac ejection fraction; Patients with a history of acute or chronic cardiovascular and cerebrovascular diseases who had relevant symptoms within 6 months prior to study drug administration: such as myocardial infarction, severe or unstable angina, cerebral infarction, cerebral hemorrhage or transient ischemic attack. Patients who have received treatment within 14 days prior to the first dose or need to continue treatment with strong CYP3A4 inducers/strong inhibitors, CYP3A4/CYP2C9/CYP2C19 sensitive substrate with a narrow treatment window or strong p-glycoprotein inhibitors. Systemic anti-tumor treatment such as standard chemotherapy, biological therapy and immunological drug therapy within 28 days prior to the first dose; targeted therapy within 14 days or 5 half-lives of the first dose (calculated as a long time); anti-tumor traditional Chinese traditional medicine treatment within 7 days prior to the first dose.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ying Cheng, Bachelor
Phone
15044044052
Email
1165095416@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jinlin Province Cancer Hosipital Cheng, Bachelor
Organizational Affiliation
Jilin Province Cancer Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jinlin Province Cancer Hosipital
City
Chang chun
State/Province
Jilin
ZIP/Postal Code
130000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ying Cheng, Bachelor
Phone
15044044052
Email
1165095416@qq.com

12. IPD Sharing Statement

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A Study of TY-1091 in Patients With Advanced Solid Tumors

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