Trial Title:
A Study of TY-2136b in Patients With Advanced Solid Tumors Harboring ALK, ROS1 or NTRK1-3 Alterations
NCT ID:
NCT05769075
Condition:
Locally Advanced Solid Tumor
Metastatic Solid Tumor
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
TY-2136b
Description:
Drug: TY-2136b PO, QD or BID
Escalation stage: 7 increased dose cohorts from low dose to MTD (from 40mg QD to 420mg
QD)
Arm group label:
Escalation stage
Intervention type:
Drug
Intervention name:
TY-2136b
Description:
Expansion stage: 4 distinct cohorts
The dose for the Expansion stage will be determined based on results from the Escalation
stage
Arm group label:
Expansion stage
Summary:
The primary objective of this study is to evaluate the safety and tolerability of
TY-2136b and to determine the recommended phase 2 dose (RP2D), with dose-escalation stage
and dose-expansion stage.
Detailed description:
- To evaluate the pharmacokinetic (PK) characteristics of TY-2136b after single and
multiple oral doses.
- To assess preliminary antitumor activity of TY-2136b as a single agent when
administered orally to patients with advanced or metastatic solid tumors.
- To identify mutations in the ALK, ROS1 and NTRK1-3, or other molecular alterations
in blood or tumor tissues associated with clinical outcome.
Criteria for eligibility:
Criteria:
Inclusion criteria:
1. Willing and able to provide written informed consent approved by institutional
review board (IRB) or independent ethics committee (IEC).
2. In the escalation stage, patients should fulfill the following criterion at
Screening:
1. Age ≥18 years.
2. Histologically or cytologically confirmed diagnosis of locally advanced or
metastatic solid tumor. Evidence of ALK, ROS1, NTRK1, NTRK2 or NTRK3
alterations in tumor tissue or blood, as determined with prior molecular assays
performed in a CLIA-certified or equivalent laboratory.
3. Patients must have failed established standard medical anti-cancer therapies
for a given tumor type or have been intolerant to such therapy, or in the
opinion of the Investigator have been considered ineligible for a particular
form of standard therapy on medical grounds. Note: Prior cytotoxic chemotherapy
is allowed; prior anti-cancer immunotherapy is allowed.
In the expansion stage, patients should fulfill the following criteria at Screening:
1. Age ≥18 years.
2. Histologically or cytologically confirmed diagnosis of locally advanced or
metastatic NSCLC and other solid tumors.
3. Subject must have a documented ROS1 or NTRK1-3 gene or ALK fusion or
rearrangement determined by CLIA-certified or equivalent testings.
Next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR)
test or fluorescence in situ hybridization (FISH).
3. ECOG Performance Status 0-1.
4. Capability to swallow intact tablet without chewing or opening; if the patient
cannot swallow many tablets of high dose at one time, the subject can take
dissolving tablets orally.
5. At least 1 measurable target lesion according to Response Evaluation Criteria in
Solid Tumor Version 1.1 (RECIST v1.1) determined by the investigator. Subjects with
central nervous system (CNS)-only measurable disease ≥10 mm as defined by RECIST
v1.1 are eligible.
6. All acute toxic effects (excluding alopecia of any prior anticancer therapy
recovered to grade ≤1 based on NCI CTCAE v5.0).
7. Patients with asymptomatic CNS metastases (treated or untreated) are also eligible
if they satisfy the other criteria specified in this protocol.
8. Baseline laboratory results fulfilling the requirements.
9. Life expectancy ≥3 months.
10. For female patients of childbearing potential, the serum or urine pregnancy test
within 72 hours prior to the start of TY-2136b treatment should be negative.
11. Male and female patients of childbearing potential must agree to use 2 methods of
highly effective contraception from signing ICF, throughout the study and continued
for 90 days after the last dose of TY-2136b treatment.
12. Willing and able to comply with all aspects of the protocol.
Exclusion criteria:
1. Concurrent participation in another therapeutic clinical trial. Unless the patient
is during follow-up period of a previous interventional clinical trial.
2. Symptomatic CNS metastases, OR leptomeningeal involvement.
3. History of other previous cancer (except for squamous cell or basal-cell carcinoma
of the skin, any in situ carcinoma that has been completely resected, or other
early-stage malignancies receiving curative treatment which get consensus between
the investigators and sponsor), requiring therapy within the previous 2 years.
4. Major surgery within 4 weeks prior to the start of TY-2136b treatment; OR radiation
therapy (except palliative to relieve bone pain) within 2 weeks prior to enrollment.
Note: Palliative radiation must have been completed at least 48 hours prior to
enrollment.
5. Patients receiving long-term systemic immunosuppressant therapy (≤10 mg/ day of
prednisone or another equivalent dose of corticosteroid inhalation or topical
administration can be included);
6. Clinically significant cardiovascular disease (either active at Screening or within
6 months prior to enrollment): myocardial infarction, unstable angina,
coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New
York Heart Association Classification Class ≥II), cerebrovascular accident or
transient ischemic attack, stroke, symptomatic bradycardia, or requirement for
anti-arrhythmic medication; or cardiac dysrhythmias of NCI CTCAE grade ≥2 deemed of
clinical significance by the investigator.
7. Any of the following cardiac criteria:
1. 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, using the screening clinic
electrocardiogram machine derived QTc value.
2. Any clinically important abnormalities in rhythm, conduction or morphology of
resting electrocardiogram (e.g., complete left bundle branch block, third
degree heart block, second degree heart block, PR interval >250 msec).
3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalemia, congenital long QT syndrome, family
history of long QT syndrome, or any concomitant medication known to prolong the
QT interval during Screening.
8. Known active infections, e.g., bacterial, fungal and viral infections, including
human immunodeficiency virus (HIV) infection (defined as anti-HIV antibody
positive), hepatitis B virus (HBV) infection [defined as Hepatitis B surface antigen
(HBsAg) positive and HBV-DNA ≥1000 cps/mL or 200 IU/mL] and hepatitis C virus (HCV)
infection (defined as anti-HCV antibody positive and HCV-RNA positive). Human
Immunodeficiency Virus (HIV) positive patients could be eligible after discussion
with medical monitor based on current and past CD4 and T-cell counts, history (if
any) of AIDS-defining conditions (e.g., opportunistic infections), and status of HIV
treatment.
9. Active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, short
gut syndrome) or other malabsorption syndromes that will impact drug absorption.
10. Peripheral neuropathy of CTCAE ≥ grade 2.
11. History of extensive, disseminated, bilateral or CTCAE grade 3 or 4 interstitial
fibrosis or interstitial lung disease (ILD) including pneumonitis, hypersensitivity
pneumonitis, interstitial pneumonia, ILD, obliterative bronchiolitis, and pulmonary
fibrosis. Note: Patients with history of prior radiation pneumonitis will not be
excluded.
12. History of strong inhibitors and/or inducers of CYP3A within 2 weeks prior to the
first dose of TY-2136b.
13. History of strong inhibitors and/or inducers of P-glycoprotein within 2 weeks prior
to the first dose of TY-2136b.
14. History of sensitive substrates and those with a narrow therapeutic index of CYP2C8,
CYP2C9, CYP2C19, CYP2D6 and CYP3A within 2 weeks prior to the first dose of
TY-2136b.
15. History of proton pump inhibitors (PPIs) within 4 days prior to the first dose of
TY-2136b; OR history of histamine H2 blockers within 2 days prior to the first dose
of TY-2136b.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Rhode Island Hospital, Brown University
Address:
City:
Providence
Zip:
02903
Country:
United States
Status:
Recruiting
Contact:
Last name:
Benedito Carneiro, MD
Phone:
401-444-3243
Email:
benedito_carneiro@brown.edu
Facility:
Name:
Oncology Consultants
Address:
City:
Houston
Zip:
30322
Country:
United States
Status:
Recruiting
Contact:
Last name:
Peguero Julio, MD
Phone:
713-600-0913
Email:
jpeguero@OncologyConsultants.com
Start date:
April 20, 2023
Completion date:
October 2025
Lead sponsor:
Agency:
TYK Medicines, Inc
Agency class:
Industry
Source:
TYK Medicines, Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05769075
