A Study of TY-2136b in Patients With Advanced Solid Tumors Harboring ALK, ROS1 or NTRK1-3 Alterations
- Conditions
- Locally Advanced Solid TumorMetastatic Solid Tumor
- Interventions
- Registration Number
- NCT05769075
- Lead Sponsor
- TYK Medicines, Inc
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 282
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Escalation stage TY-2136b Escalation stage: Multiple doses of TY-2136b for oral administration to find the maximum tolerated dose Expansion stage TY-2136b Expansion stage: 4 distinct expansion cohorts
- Primary Outcome Measures
Name Time Method (Escalation stage) Dose Limiting Toxicities (DLTs) Within 28 days of the first dose Numbers of participants experiencing AEs which are defined as DLTs classfied by CTCAE v5.0.
(Escalation stage) Adverse events (AEs) From Baseline up to 28 days after the end of the treatment Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
(Escalation stage) Recommended Phase 2 Dose (RP2D) Within 28 days of the last patient dosed in escalation stage 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.
(Expansion stage) Overall Response Rate (ORR) 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. 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).
- Secondary Outcome Measures
Name Time Method (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) Cmax is the maximum (or peak) plasma concentration that the drug achieves in blood after the drug has been administered.
(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) Cmin is the minimum plasma concentration that the drug achieves in blood after the drug has been administered.
(Escalation and Expansion stage) Progression-free survival (PFS) Up to 30 months after the date of first dose. PFS is defined as the time from randomization until first evidence of disease progression or death.
(Escalation and Expansion stage) Duration of Response (DOR) Up to 30 months after the date of first dose. DOR is defined as the time from randomization to disease progression or death in patients who achieve complete or partial response.
(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) AUC0-t defined as area under the plasma concentration-time curve from time 0 to time t.
(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) AUC0-inf defined as the area under the plasma concentration-time curve from time 0 extrapolated to Infinite time.
(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) T1/2 is defined as the time for the concentration of a compound in sytemic circulation to reduce by half.
(Escalation and Expansion stage) The time to the peak concentration (Tmax) Cycle1 Day 1 and Cycle1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days) Tmax is defined as the time of maximum concentration of the drug in blood observed after a drug dose administration.
(Escalation stage) Overall Response Rate (ORR) 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. 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).
(Escalation and Expansion stage) Overall survival (OS) Up to 30 months after the date of first dose. OS is defined as the time from the start of treatment to death or the end of the study.
Trial Locations
- Locations (2)
Oncology Consultants
🇺🇸Houston, Texas, United States
Rhode Island Hospital, Brown University
🇺🇸Providence, Rhode Island, United States