A Study of TY-9591 in Advanced Non-small Cell Lung Cancer(NSCLC) Patients With EGFR Positive Mutation

NCT04204473 | Completed Phase 1

• 1 other identifier: TYKM1601101
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of TY-9591, with dose-escalation stage and dose-expansion stage.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicity (DLT)

  Incidence of Dose Limiting Toxicity (DLT)

  First 29 days of dosing

• Maximum Tolerated Dose (MTD)

  To determine the Maximum Tolerated Dose (MTD) of TY-9591 in subjects with NSCLC

  1year

• Recommended Phase 2 dose (RP2D)

  Recommended Phase 2 dose (RP2D) of TY-9591 in subjects with NSCLC

  through study completion, an average of 2.5 years

• Overall Response Rate (ORR)

  ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  At least 24 weeks

Secondary Outcomes (8)

• Cmax

  pharmacokinetics(PK) blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12, 24, 48, 72,96,120,144,168 and 192 hours post-dose.

• Tmax

  pharmacokinetics(PK) blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12, 24, 48, 72,96,120,144,168 and 192 hours post-dose.

• Area Under Curve(AUC)

  pharmacokinetics(PK) blood samples are collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10,12, 24, 48, 72,96,120,144,168 and 192 hours post-dose

• Cmax

  The datas should be evaluated multiple times on Cycle 1 day1,8,15, 21 pre-dose; Cycle 2 day1 (at pre-dose, 0.5,1, 2, 3, 4, 6, 8, 10,12, 24 hours post-dose). Each cycle is 21 days

• Cmin

  The datas should be evaluated multiple times on Cycle 1 day1,8,15, 21 pre-dose; Cycle 2 day1 (at pre-dose, 0.5,1, 2, 3, 4, 6, 8, 10,12, 24 hours post-dose). Each cycle is 21 days

Study Arms (1)

TY-9591

EXPERIMENTAL

Find maximum tolerated dose of TY-9591 given orally. Escalating doses of TY-9591 starting at 20mg daily.

Drug: TY-9591(10mg,40mg) qd. po

Interventions

TY-9591(10mg,40mg) qd. po DRUG

Increased dose cohorts from low dose to MTD(20mg Cohort1, 40mg Cohort2, 80mg Cohort3,120mg Cohort4, 160mg Cohort5, 200mg Cohort6)

Also known as: TY-9591

TY-9591

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old, male or female.
• Histological or cytological confirmation diagnosis of NSCLC
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
• Life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
• Documentation of disease progression while on previous continuous treatment with first-line EGFR TKI; patients must have confirmation of tumor EGFR activating mutations (exon 19 del, or exon 21 ) and T790M mutation status
• Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• a.Neutrophils (absolute value) ≥ 1.5×10\^9/L; b.Hemoglobin ≥ 90 g/L; c.Platelet ≥ 80×10\^9/L; d.Serum total bilirubin ≤ 1.5× ULN（for Patients with Gilbert Syndrome, total bilirubin ≤ 3×ULN and bilirubin ≤ 1.5×ULN should be permitted） f. Aspartate aminotransferase(AST)、alanine aminotransferase(ALT) ≤ 2.5×ULN; for patients with hepatic metastases, AST、ALT ≤ 5×ULN; g. International standardized ratio (INR) \< 1.5, and activated partial prothrombin time (APTT) \< 1.5×ULN;
• Female subjects have a negative urine or serum pregnancy.
• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.

You may not qualify if:

• Treatment with any of the following:
• Treatment with an EGFR TKI within 14 days or about 5x half-life, whichever is the longer, of the first dose of study drug;
• Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the treatment from a previous treatment regimen within 4 weeks of the first dose of study treatment;
• Major surgery within 4 weeks of the first dose of study treatment;
• Radiotherapy with a limited field of radiation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation that had to be completed within 4 weeks of the first dose of study treatment;
• Previously treated by other third-generation epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) for T790M (for example Osimertinib).
• Patients currently receiving (or at least within 1 week prior to receiving the first dose )medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 isoenzyme (CYP)3A4.
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
• Spinal cord compression or brain metastases unless asymptomatic.
• Dysphagia, or active digestive system diseases or previous significant bowel resection or medical conditions potentially affect TY-9591 absorption.
• Cardiac function and disease are consistent with the following:
• Corrected QT interval(QTc)\> 470 milliseconds from 3 electrocardiograms (ECGs);
• Any clinically important abnormalities in rhythm;
• Any factors that increase the risk of QTc prolongation;
• Left ventricular ejection fraction (LVEF) \<50%;

Sponsors & Collaborators

• TYK Medicines, Inc: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, 201203, China

Location

Study Officials

• Baohui Han, MD

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: December 19, 2019
• Study Start: May 7, 2020
• Primary Completion: March 3, 2023
• Study Completion: May 18, 2023
• Last Updated: November 18, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)