NCT04204473CompletedPhase 1
Phase I, Open-label, Single-arm Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Preliminary Efficacy of TY-9591 Tablets in Advanced NSCLC Patients With Epidermal Growth Factor Receptor( EGFR) Positive Mutation
Conditions
Interventions
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- TYK Medicines, Inc
- Enrollment
- 105
- Locations
- 1
- Primary Endpoint
- Recommended Phase 2 dose (RP2D)
Study Overview
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.
Detailed Description
- To define the maximum tolerated dose(MTD) and the recommended phase 2 dose (RP2D)
- To investigate the pharmacokinetic profile of TY-9591 and its metabolites after single then multiple doses of TY-9591 administered orally once daily
- To evaluate the anti-cancer activity of TY-9591 in NSCLC patients with EGFR mutation(ORR、PFS、DoR、DCR、and CBR)
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •18-75years 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.
- •Life expectancy of at least 3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance score 0 or
- •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.
Exclusion Criteria
- •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)3A
- •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%;
- •Active human immunodeficiency virus (HIV), syphilis, hepatitis c virus (HCV) or hepatitis b virus (HBV) infection, with the exception of asymptomatic chronic hepatitis b or hepatitis c carriers.
- •7 .Previous history of interstitial lung disease(ILD)、drug-induced ILD or radiation pneumonitis require steroid treatment, or any evidence of clinically active ILD diseases.
- •Previous allogeneic bone marrow transplant.
- •Hypersensitivity to TY-9591 or similar compounds or excipients. 10.Pregnant or lactating women.
Arms & Interventions
TY-9591
Experimental
Find maximum tolerated dose of TY-9591 given orally. Escalating doses of TY-9591 starting at 20mg daily.
Intervention: TY-9591(10mg,40mg) qd. po (Drug)
Outcomes
Primary Outcomes
Recommended Phase 2 dose (RP2D)
Time Frame: through study completion, an average of 2.5 years
Recommended Phase 2 dose (RP2D) of TY-9591 in subjects with NSCLC
Dose Limiting Toxicity (DLT)
Time Frame: First 29 days of dosing
Incidence of Dose Limiting Toxicity (DLT)
Maximum Tolerated Dose (MTD)
Time Frame: 1year
To determine the Maximum Tolerated Dose (MTD) of TY-9591 in subjects with NSCLC
Overall Response Rate (ORR)
Time Frame: At least 24 weeks
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)
Secondary Outcomes
- 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)
- Duration of Response (DOR)(9.7 months)
- 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)
- 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)
- AUC(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)
- 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.)
- Progression-free survival (PFS)(10.1 months)
Investigators
Study Sites (1)
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