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

NCT05675605 | Unknown Phase 1

• 1 other identifier: TYKM3604102
• Study Type: interventional
• Target: 248
• Locations: 1 country
• Sites: 1

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.

Conditions

RET-altered Non Small Cell Lung Cancer; Medullary Thyroid Cancer; RET-altered Papillary Thyroid Cancer; Neoplasms

Outcome Measures

Primary Outcomes (3)

• (Phase 1 )Dose Limiting Toxicity (DLT)

  First 25 days of dosing

• (Phase 1) Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Approximately 12 months

• (Phase 2) Overall Response Rate (ORR)

  up to 24 weeks

Secondary Outcomes (18)

• (Phase 1) Overall Response Rate (ORR)

  up to 24 weeks

• iORR

  up to 24 weeks

• DCR

  up to 24 weeks

• CBR

  1 year

• DOR

  Approximately 1 year

Study Arms (2)

Phase 1 Dose Escalation

EXPERIMENTAL

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

Drug: TY-1091

Phase 2 Dose Expansion

EXPERIMENTAL

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

Drug: TY-1091

Interventions

TY-1091 DRUG

TY-1091(10mg,100mg) , once a day, oral administration Dose level is from 20mg to 800mg

Phase 1 Dose Escalation; Phase 2 Dose Expansion

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• TYK Medicines, Inc: lead

Study Sites (1)

Jinlin Province Cancer Hosipital

Changchun, Jilin, 130000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Medullary; Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue

Study Officials

• Jinlin Province Cancer Hosipital Cheng, Bachelor

  Jilin Province Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Cheng, Bachelor

CONTACT

15044044052; 1165095416@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: January 9, 2023
• Study Start: April 24, 2023
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 30, 2024

Record last verified: 2024-01

Locations

CN (1)