There are 3 clinical trials
The main objective of this study is to evaluate the safety and tolerability of BPI-15086.
icotinib, gefitinib, afatinib, neratinib, dacomitnib, or erlotinib) treatment - Patients must fulfil one of the following: - Confirmation that the tumour harbours EGFR sensitivity mutation (exon 19 deletion, L858R and L861R, G719X) - Must have experienced clinical benefit from EGFR TKIs, according to the Jackman criteria - Confirmation of T790M mutation positive after disease progression on EGFR TKIs - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and estimated life expectancy of at least 12 weeks - Measurable lesion per Response Evaluation Criteria in Solid Tumors(RECIST1.1) --- L858R --- --- L861R ---
Description: Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03Measure: Adverse events Time: 18 months
This is a single center and exploratory study, aiming to analyze the efficacy and safety of dacomitinib-a pan-HER and irreversible TKI in subjects with diagnosed stage IIIB/IV or recurrent NSCLC. All subjects will have tumors that test positive for at least one uncommon EGFR activating mutation (do not have drug-resistant pattern, e.g. 20 insertion or 20T790M). All patients will be of histo- and/or cytopathology confirmed. Determination of the EGFR mutation type will be performed in the pathological department of Shanghai Chest Hospital. Both ARMS method or targeted sequencing are acceptable. It is not acceptable for subjects with the presence of the exon 20T790M mutation or insertion together with either EGFR activating mutations (exon 19 deletion or the L858R mutation in exon 21) or uncommon EGFR mutations. 10ml peripheral blood must be available for concomitant study. All eligible subjects must have adequate renal, hepatic, and hematologic function, as defined in "inclusion criteria". Patients will receive continuous oral therapy with the study drugs (dacomitinib 45 mg) until progressive disease as defined by RECIST version 1.1 or judged by investigator that the patient no longer derives clinical benefit from study treatment. At the time of progression and removal from study treatment, the subject may receive any regulatory approved therapy at the judgment of the investigator. Timely and complete disease assessments in this study are important. Every effort should be made to ensure disease assessments performed as scheduled to prevent the introduction of bias into the assessment of efficacy. Failure to perform any of the required disease assessments will result in the inability to determine disease status for that time point. Frequent off schedule or incomplete disease assessments have the potential to weaken the study conclusion. Subjects who have progressive disease per RECIST version 1.1 confirmed by the investigator believes it is in their best interest to continue on their study therapy, will be allowed to continue on their therapy with or without local therapy (e.g. surgical removal and/or radiation of a single lesion), at the discretion of the investigator until any alternate or additional systemic anti-cancer therapy regimen is implemented. The subsequent new cancer therapy (including, for systemic therapy, drugs administered, date of initiation and discontinuation of each drug) and OS will be recorded. Each subject will be followed for survival status and subsequent cancer therapies up to 48 months from the date of first dosing. This data may be collected from subjects by telephone, and if collected should be entered into the CRF.
Mutation in exon 20: Including S768I, V765A, T783A, V774A, S784P, R776C, R776H, V765M, G779C, G779F, G779S, T783A, T783I, L798F, L798H, K806E, Q812R, L814P Mutation in exon 21: L861Q, R831H, V834I, L838P, L861R. --- S768I --- --- V765A --- --- T783A --- --- V774A --- --- S784P --- --- R776C --- --- R776H --- --- V765M --- --- G779C --- --- G779F --- --- G779S --- --- T783A --- --- T783I --- --- L798F --- --- L798H --- --- K806E --- --- Q812R --- --- L814P --- --- L861Q --- --- R831H --- --- V834I --- --- L838P --- --- L861R ---
Description: ORR was defined as the proportion of patients with a complete response (CR) or partial response (PR) per the investigator's assessment using RECIST 1.1 criteriaMeasure: Objective response rate （ORR） Time: 6-12 weeks
Description: The disease control rate (DCR) was defined as the sum of the proportions of patients who had CR, PR, and stable disease (SD) using RECIST 1.1 criteriaMeasure: Disease control rate Time: 6-12 weeks
Description: PFS was defined as the time from study treatment initiation to the first occurrence of documented disease progression or death from any cause during the study, whichever occurred first.Measure: PFS Time: 13-15months
Description: OS was defined as the time from the first dose of study treatment to the time of death from any cause during the study.Measure: Overall survival Time: 22-25months
The purpose of this phase 1/2 study is to evaluate the safety, recommended phase 2 dose (RP2D), dose limiting toxicities (DLTs), maximum tolerated dose (MTD), pharmacokinetics of oral TAK-788 and its active metabolites, anti-tumor activity of TAK-788 in participants with NSCLC with epidermal growth factor receptor (EGFR) or human epidermal growth factor 2 (HER2) mutations, explore relationship between tumor and/or plasma biomarkers and TAK-788 efficacy, safety, and/or cytochrome P450 (CYP) 3A induction (in Part 1 [Dose Escalation Component] and Part 2 [Expansion Cohorts] for oral TAK-788) and (in Part 1A [Dose Escalation Combination Component] when TAK-788 is taken in combination with pemetrexed/carboplatin), and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations in Parts 1 and 2.
Part 2: Expansion Cohort 4 Specific Inclusion Criteria: 1. Have one of the following documented by a local test: an activating mutation in EGFR including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or an uncommon activating mutation other than exon 20 insertion including, but not limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R. --- L858R --- --- T790M --- --- S768I --- --- L861Q --- --- L861R ---
Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.Measure: Part 1A, Dose Escalation Combination Component: RP2D/MTD of Orally Administered TAK 788 in Combination With Pemetrexed/ Carboplatin Time: Up to Cycle 2 (Cycle length=21 days)
Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.Measure: Part 1A, Dose Escalation Combination Component: Identify DLTs of Orally Administered TAK 788 in Combination With Pemetrexed/ Carboplatin Time: Up to Cycle 2 (Cycle length=21 days)
Description: This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.Measure: Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: Safety Analysis of TAK-788 and when TAK-788 Given in Combination With Pemetrexed/ Carboplatin Assessed by Adverse Events, Toxicity Grades, and Laboratory Test Results Time: Up to 36 months after first dose