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

January 28, 2024 updated by: TYK Medicines, Inc

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

248

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jilin
      • Chang chun, Jilin, China, 130000
        • Recruiting
        • Jinlin Province Cancer Hosipital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.

  2. 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.
  3. Life expectancy of at least 3 months.
  4. Adequate organ functions.
  5. Ability to swallow capsules and willing and able to provide written informed consent approved by institutional review board (IRB) or independent ethics committee (IEC).
  6. 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:

  1. For NSCLC patients, a targetable mutation in EGFR or MET, targetable rearrangement involving ALK, ROS1 or NTRK1-3.
  2. 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.
  3. 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.
  4. Symptomatic primary central nervous system (CNS) tumor or metastases; symptomatic leptomeningeal carcinomatosis; untreated spinal cord compression.

  5. 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.

  6. 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.
  7. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1 Dose Escalation
Multiple doses of TY-1091 for oral administration. Intervention: Drug: TY-1091
Drug: TY-1091
TY-1091(10mg,100mg) , once a day, oral administration Dose level is from 20mg to 800mg
Experimental: Phase 2 Dose Expansion
Multiple doses of TY-1091 for oral administration. Intervention: Drug: TY-1091
Drug: TY-1091
TY-1091(10mg,100mg) , once a day, oral administration Dose level is from 20mg to 800mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
(Phase 1 )Dose Limiting Toxicity (DLT)
Time Frame: First 25 days of dosing
First 25 days of dosing
(Phase 1) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Approximately 12 months
Approximately 12 months
(Phase 2) Overall Response Rate (ORR)
Time Frame: up to 24 weeks
up to 24 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
(Phase 1) Overall Response Rate (ORR)
Time Frame: up to 24 weeks
up to 24 weeks
iORR
Time Frame: up to 24 weeks
up to 24 weeks
DCR
Time Frame: up to 24 weeks
up to 24 weeks
CBR
Time Frame: 1 year
1 year
DOR
Time Frame: Approximately 1 year
Approximately 1 year
PFS
Time Frame: Up to approximately 33 months
Up to approximately 33 months
OS
Time Frame: Up to approximately 33 months
Up to approximately 33 months
(Phase 1 and 2) Pharmacokinetic Parameters Including Maximum Plasma Drug Concentration (Cmax)
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 and 2) Pharmacokinetic Parameters Including Terminal Elimination Half-life (t1/2)
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 ) AUC0-24
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 and 2) Pharmacokinetic Parameters Including Tmax
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 and 2) Pharmacokinetic Parameters Including Cmin
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 ) AUC0-t
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 ) AUCinf
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 ) inflearance rate constant (Kel)
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 ) apparent clearance (CL/F)
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 ) Vd/F
Time Frame: First 46 days of dosing
First 46 days of dosing
(Phase 1 ) mean residence time (MRTinf)
Time Frame: First 46 days of dosing
First 46 days of dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

TYK Medicines, Inc

Investigators

  • Principal Investigator: Jinlin Province Cancer Hosipital Cheng, Bachelor, Jilin Province Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 24, 2023

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

December 9, 2022

First Submitted That Met QC Criteria

December 21, 2022

First Posted (Actual)

January 9, 2023

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 28, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TYKM3604102

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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