Evaluating TY-1091 for patients with advanced solid tumors

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 study is testing a new drug called TY-1091 to see if it is safe and effective for people with advanced solid tumors, especially those with certain types of lung and thyroid cancers that haven't responded to other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 248 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: TYK Medicines, Inc (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Chang chun, Jilin)
• Trial ID: NCT05675605 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of TY-1091 in patients with advanced solid tumors, specifically focusing on RET-altered non-small cell lung cancer, medullary thyroid cancer, and other RET-altered tumors. The study is divided into two parts: a dose-escalation phase (Phase 1) and a dose expansion phase (Phase 2). Participants must have advanced tumors that are non-resectable and have either progressed after standard therapy or for whom standard therapy is not appropriate. The study will utilize a multicenter, open-label design to gather data on the drug's performance.

Who should consider this trial

Good fit: Ideal candidates include patients with RET-altered non-small cell lung cancer, medullary thyroid cancer, or other advanced solid tumors who have not responded to standard treatments.

Not a fit: Patients with early-stage tumors that are resectable or those without RET gene alterations may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors that are difficult to treat with existing therapies.

How similar studies have performed: While this approach is novel in its specific targeting of RET-altered tumors, similar studies targeting specific genetic alterations have shown promise in the past.

Eligibility criteria

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.

Where this trial is running

Chang chun, Jilin

• Jinlin Province Cancer Hosipital — Chang chun, Jilin, China (Recruiting)

Study contacts

• Principal investigator: Jinlin Province Cancer Hosipital Cheng, Bachelor — Jilin Province Cancer Hospital
• Study coordinator: Ying Cheng, Bachelor

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