A Study of TY-2136b in Patients With Advanced Solid Tumors Harboring ALK, ROS1 or NTRK1-3 Alterations

NCT05769075 | Unknown Phase 1 FDA Drug

• 1 other identifier: TYKM7203101
• Study Type: interventional
• Target: 282
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Locally Advanced Solid Tumor; Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (4)

• (Escalation stage) Dose Limiting Toxicities (DLTs)

  Numbers of participants experiencing AEs which are defined as DLTs classfied by CTCAE v5.0.

  Within 28 days of the first dose

• (Escalation stage) Recommended Phase 2 Dose (RP2D)

  The RP2D is defined as the dose level chosen for the dose expansion arms, based on safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study.

  Within 28 days of the last patient dosed in escalation stage

• (Escalation stage) Adverse events (AEs)

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

  From Baseline up to 28 days after the end of the treatment

• (Expansion stage) Overall Response Rate (ORR)

  ORR is defined as the percentage of subjects who have a partial response (PR) or complete response (CR) to the treatment response assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

  From the date of first dose until the date of first documented progression or stable disease or the date of death from any cause, whichever came first, assessed up to 30 months.

Secondary Outcomes (10)

• (Escalation and Expansion stage) Area under the plasma concentration time curve(AUC0-inf)

  Cycle 1 Day 1 (at pre-dose, 0.5, 1, 2, 4, 6, 24 h post-dose) (Each Cycle=28 days)

• (Escalation and Expansion stage) Area under the plasma concentration time curve(AUC0-t)

  Cycle 1 Day 1 and Cycle 1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days)

• (Escalation and Expansion stage) Maximum plasma concentration (Cmax)

  Cycle 1 Day1 and Cycle 1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days)

• (Escalation and Expansion stage) Minimum plasma concentration (Cmin)

  Cycle1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days)

• (Escalation and Expansion stage) Terminal half-life (t1/2)

  Cycle1 Day 1 and Cycle1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days)

Study Arms (2)

Escalation stage

EXPERIMENTAL

Escalation stage: Multiple doses of TY-2136b for oral administration to find the maximum tolerated dose

Drug: TY-2136b

Expansion stage

EXPERIMENTAL

Expansion stage: 4 distinct expansion cohorts

Drug: TY-2136b

Interventions

TY-2136b DRUG

Drug: TY-2136b PO, QD or BID Escalation stage: 7 increased dose cohorts from low dose to MTD (from 40mg QD to 420mg QD)

Escalation stage

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent approved by institutional review board (IRB) or independent ethics committee (IEC).
• In the escalation stage, patients should fulfill the following criterion at Screening:
• Age ≥18 years.
• 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.
• 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:
• Age ≥18 years.
• Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC and other solid tumors.
• 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).
• ECOG Performance Status 0-1.
• 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.
• 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.
• All acute toxic effects (excluding alopecia of any prior anticancer therapy recovered to grade ≤1 based on NCI CTCAE v5.0).
• Patients with asymptomatic CNS metastases (treated or untreated) are also eligible if they satisfy the other criteria specified in this protocol.
• Baseline laboratory results fulfilling the requirements.

You may not qualify if:

• Concurrent participation in another therapeutic clinical trial. Unless the patient is during follow-up period of a previous interventional clinical trial.
• Symptomatic CNS metastases, OR leptomeningeal involvement.
• 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.
• 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.
• 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);
• 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.
• Any of the following cardiac criteria:
• 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.
• 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).
• 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.
• 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.
• Active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) or other malabsorption syndromes that will impact drug absorption.
• Peripheral neuropathy of CTCAE ≥ grade 2.
• 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.
• History of strong inhibitors and/or inducers of CYP3A within 2 weeks prior to the first dose of TY-2136b.

Sponsors & Collaborators

• TYK Medicines, Inc: lead

Study Sites (2)

Rhode Island Hospital, Brown University

Providence, Rhode Island, 02903, United States

RECRUITING

Oncology Consultants

Houston, Texas, 30322, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• TYK Medicines, Inc

  TYK Medicines, Inc

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: March 15, 2023
• Study Start: April 20, 2023
• Primary Completion: January 1, 2025
• Study Completion: October 1, 2025
• Last Updated: April 24, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)