The purpose of this study is to evaluate the safety, efficacy, tolerability and pharmacokinetics (PK) of TAK-788. At first, Phase 1 part of this study is designed to determine a recommended phase 2 dose (RP2D) of TAK-788 in Japanese participants with locally advanced or metastatic non-small cell lung cancer (NSCLC). After phase 1 study, the phase 2 part of this study will be conducted to evaluate the efficacy and safety of TAK-788 in treatment naive Japanese NSCLC patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutation.
Name: TAK-788
Description: The RP2D is the maximum tolerated dose (MTD) or less. An RP2D less than the MTD may be chosen if aspects of tolerability or efficacy not encompassed by the MTD determination suggest utilizing a lower dose.
Measure: Phase 1 Part: Recommended Phase 2 Dose (RP2D) of Orally Administered TAK-788 Time: Up to approximately 28 daysDescription: IRC assessed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in participants with epidermal growth factor receptor (EGFR) or human epidermal growth factor 2 (HER2) mutations. ORR is defined as the percentage of participants achieving complete response (CR) and partial response (PR) per RECIST version 1.1. CR: Disappearance of all extranodal target lesions; PR: At least a 30% decrease in Sum of the Longest Diameters (SLD) of target lesions, taking as a reference the baseline SLD.
Measure: Phase 2 Part: Overall Response Rate (ORR) as Assessed by the Independent Review Committee (IRC) Time: Up to approximately 1.5 yearsDescription: An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Measure: Phase 1 Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Time: Up to approximately 1.5 yearsDescription: Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.00. DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications.
Measure: Phase 1 Part: Number of Participants with First Cycle Dose-Limiting Toxicities (DLTs) Time: Up to approximately 1.5 yearsDescription: Toxicity will be evaluated according to the NCI CTCAE, Version 5.00. DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications.
Measure: Phase 1 Part: DLTs of Orally Administered TAK-788 Time: Up to approximately 28 daysDescription: The MTD is the highest dose level at which the participant tolerates treatment without dose-limiting toxicities.
Measure: Phase 1 Part: Maximum Tolerated Dose (MTD) of Orally Administered TAK-788 Time: Up to approximately 28 daysDescription: IRC assessed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in participants with epidermal growth factor receptor (EGFR) or human epidermal growth factor 2 (HER2) mutations. ORR is defined as the percentage of participants achieving complete response (CR) and partial response (PR) per RECIST version 1.1. CR: Disappearance of all target lesions; PR: At least a 30% decrease in SLD of target lesions, taking as a reference the baseline SLD.
Measure: Phase 2 Part: Overall Response Rate (ORR) as Assessed by the Independent Review Committee (IRC) Time: Up to approximately 4 yearsDescription: Duration of response is defined as the time interval from the time that the measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that PD is objectively documented.
Measure: Phase 2 Part: Duration of Response (DOR) Time: Up to approximately 4 yearsDescription: Time to response is defined as the time interval from the date of randomization until the initial observation of CR or PR.
Measure: Phase 2 Part: Time to Response Time: Up to approximately 4 yearsDescription: DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) (in the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 42 days) after the initiation of study drug.
Measure: Phase 2 Part: Disease Control Rate (DCR) Time: Up to approximately 4 yearsDescription: PFS is defined as the time interval from the date of randomization until the first date at which the criteria for progressive disease (PD) according to RECIST version 1.1 are met or death, whichever occurs first.
Measure: Phase 2 Part: Progression Free Survival (PFS) Time: Up to approximately 4 yearsDescription: OS is defined as the interval from the date of randomization until death.
Measure: Phase 2 Part: Overall Survival (OS) Time: Up to approximately 4 yearsDescription: EORTC QLQ-C30 is a cancer-specific questionnaire which comprises of 5 functional scales (physical, role, cognitive, emotional, and social functioning); 3 symptom scales (fatigue, pain, and nausea/vomiting); and a global health status/quality-of-life (QoL) scale. Six single-item scales are also included (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Raw scores will be converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QoL scale, higher scores represent better HRQoL, whereas for the symptom scales lower scores represent better HRQoL (i.e., a low level of symptomatology/problems).
Measure: Phase 2 Part: Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Time: Up to approximately 4 yearsDescription: EORTC QLQ-LC13 contains 13 questions to assess for: dyspnea, and a series of single items including pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. Score of each item will range from 0 to 100, where 0 indicates no symptoms and 100 indicates worst possible symptoms.
Measure: Phase 2 Part: Patient-reported Symptoms (particular core symptoms of lung cancer), Functioning, and HRQoL as Assessed by the EORTC lung cancer module QLQ-LC13 Time: Up to approximately 4 yearsAllocation: Non-Randomized
Single Group Assignment
There is one SNP
The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations except EGFR common mutations (exon 19 del or L858R). --- L858R ---