NLP SNP

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 ---

Primary Outcomes

Description: Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03

Measure: Adverse events

Time: 18 months

Secondary Outcomes

Measure: Cmax

Time: 4 weeks

Measure: Half life

Time: 4 weeks

Measure: AUC

Time: 4 weeks

Measure: Objective Response Rate

Time: 12 weeks

Measure: Progression-Free Survival

Time: 18 months

2 A Phase 1/2 Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of the Oral EGFR/HER2 Inhibitor TAK-788 (AP32788) in Non-Small Cell Lung Cancer

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, anti-tumor activity of TAK-788 in participants with NSCLC with epidermal growth factor receptor (EGFR) or human epidermal growth factor 2 (HER2), and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations, and to explore relationship between tumor and/or plasma biomarkers, and TAK-788 efficacy, safety, and/or cytochrome P450 3A (CYP3A) induction. The study will also determine the efficacy of TAK-788 in participants with locally advanced metastatic NSCLC harboring EGFR in-frame exon 20 insertion mutations who have received at least 1 prior line of therapy for locally advanced or metastatic NSCLC.

NCT02716116 Carcinoma, Non-Small-Cell Lung Drug: TAK-788

MeSH: Carcinoma, Non-Small-Cell Lung

HPO: Non-small cell lung carcinoma

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 ---

Primary Outcomes

Measure: Dose Escalation Cohort: RP2D of Orally Administered TAK-788

Time: Day 1 to 28 (Cycle 1)

Measure: Expansion Cohorts 1, 2, 4, 5, 6, and 7: Objective Response Rate (ORR)

Time: up to 36 months after first dose

Measure: Expansion Cohort 3: Intracranial ORR (iORR)

Time: up to 36 months after first dose

Measure: Extension Cohort: Confirmed ORR as per Independent Review Committee (IRC)

Time: up to 36 months after first dose

Secondary Outcomes

Measure: Dose Escalation and Expansion Cohorts: Safety Analysis of TAK-788 Assessed by Adverse Events, Toxicity Grades, and Laboratory Test Results

Time: up to 36 months after first dose

Measure: Dose Escalation Cohort: Identify DLTs and MTD of TAK-788

Time: Day 1 to 28 in Cycle 1 (Cycle length is equal to [=] 28 days)

Measure: Dose Escalation and Expansion Cohorts: Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax)

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)

Measure: Dose Escalation and Expansion Cohorts: AUC24: Area Under the Concentration-time Curve from Time Zero to 24 hours for TAK-788 and its Metabolites

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)

Measure: Dose Escalation and Expansion Cohorts: AUCt: Area Under the Concentration-time Curve from Time Zero to Time t for TAK-788 and its Metabolites

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)

Measure: Dose Escalation and Expansion Cohorts: RAC (Cmax): Accumulation Ratio Based on Cmax of TAK-788 and its Metabolites

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)

Measure: Dose Escalation and Expansion Cohorts: Ctrough: Observed Concentration at the end of a Dosing Interval of TAK-788 and its Metabolites

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)

Measure: Dose Escalation and Expansion Cohorts: RAC (AUC): Accumulation Ratio Based on AUC of TAK-788 and its Metabolites

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)

Measure: Dose Escalation and Expansion Cohorts: Cmax: Maximum Observed Concentration of TAK-788 and its Metabolites

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)

Measure: Expansion Cohorts: ORR as Assessed by IRC

Time: up to 36 months after first dose

Measure: Expansion Cohorts: Best Overall Response as Assessed by the Investigator and IRC

Time: up to 36 months after first dose

Measure: Expansion Cohorts: Best Target Lesion Response as Assessed by the Investigator and IRC

Time: up to 36 months after first dose

Measure: Expansion and Extension Cohorts: Duration of Response as Assessed by the Investigator and IRC

Time: up to 36 months after first dose

Measure: Expansion and Extension Cohorts: Time to Response as Assessed by the Investigator and IRC

Time: up to 36 months after first dose

Measure: Expansion Cohort 3: Duration of Intracranial Response (iDOR)

Time: up to 36 months after first dose

Measure: Expansion and Extension Cohorts: Disease Control Rate (DCR) as Assessed by the Investigator and IRC

Time: up to 36 months after first dose

Measure: Expansion and Extension Cohorts: Progression Free Survival (PFS) as Assessed by the Investigator and IRC

Time: up to 36 months after first dose

Measure: Expansion Cohort 3: Intracranial PFS (iPFS)

Time: up to 36 months after first dose

Measure: Expansion and Extension Cohorts: Overall Survival (OS)

Time: up to 36 months after first dose

Measure: Extension Cohort: Confirmed ORR as Assessed by the Investigator

Time: up to 36 months after first dose

Measure: Dose Escalation and Expansion Cohorts: Cmax: Dose Linearity for TAK-788 Exposure

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)

Measure: Dose Escalation and Expansion Cohorts: AUC: Dose Linearity for TAK-788 Exposure

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days)

Measure: Extension Cohort: Change from Baseline in Global Quality of Life (QoL) Based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30)

Time: Baseline up to 30 days after last dose of drug (approximately up to 37 months)

Measure: Extension Cohort: Change from Baseline in Dyspnea Scale Based on Quality of Life Questionnaire Lung Cancer Module-13 (QLQ-LC13)

Time: Baseline up to 30 days after last dose of drug (approximately up to 37 months)

HPO Nodes

Non-small cell lung carcinoma

Genes 2

TP53 BAP1

Neoplasm of the lung

Genes 43

WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN