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

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Secondary Outcomes

Measure: Cmax

Time: 4 weeks

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Measure: Half life

Time: 4 weeks

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Measure: AUC

Time: 4 weeks

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Measure: Objective Response Rate

Time: 12 weeks

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Measure: Progression-Free Survival

Time: 18 months

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Primary Outcomes

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 criteria

Measure: Objective response rate （ORR）

Time: 6-12 weeks

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Secondary Outcomes

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 criteria

Measure: Disease control rate

Time: 6-12 weeks

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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

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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

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Primary Outcomes

Measure: Part 1, Dose Escalation Component: RP2D of Orally Administered TAK-788

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

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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)

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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)

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Measure: Part 2, Expansion Cohorts 1, 2, 4, 5 and 7: Confirmed Objective Response Rate (ORR) Assessed by the Investigator

Time: Up to 36 months after first dose

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Measure: Part 2, Expansion Cohort 3: Intracranial ORR (iORR) Assessed by Independent Review Committee (IRC)

Time: Up to 36 months after first dose

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Measure: Part 2, Expansion Cohort 6: Confirmed ORR Assessed by IRC

Time: Up to 36 months after first dose

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Measure: Part 3, Extension Cohort: Confirmed ORR Assessed by IRC

Time: Up to 36 months after first dose

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Secondary Outcomes

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

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Measure: Part 1, Dose Escalation Component: Identify DLTs and MTD of TAK-788

Time: Cycle 1 (Cycle length=28 days)

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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: Cmax; Maximum Observed Concentration of TAK-788 and its Metabolites

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A)

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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: Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of TAK-788 and its Metabolites

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A)

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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: AUC 24; 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 for Parts 1 and 2, and 21 days for Part 1A)

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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: 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 for Parts 1 and 2, and 21 days for Part 1A)

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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: 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 for Parts 1 and 2, and 21 days for Part 1A)

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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: 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 for Parts 1 and 2, and 21 days for Part 1A)

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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: Cmax: Dose Proportionality for TAK-788 Exposure

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A)

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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: AUC: Dose Proportionality for TAK-788 Exposure

Time: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A)

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Measure: Part 2, Expansion Cohorts 1, 2, 3, 4, 5, and 7: Confirmed ORR as Assessed by IRC

Time: Up to 36 months after first dose

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Measure: Part 2, Expansion Cohorts: Best Overall Response as Assessed by the Investigator and IRC

Time: Up to 36 months after first dose

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Measure: Part 2, Expansion Cohorts: Best Target Lesion Response as Assessed by the Investigator and IRC

Time: Up to 36 months after first dose

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Measure: Parts 2 and 3, Expansion and Extension Cohorts: Duration of Response as Assessed by the Investigator and IRC

Time: Up to 36 months after first dose

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Measure: Part 2 and 3, Expansion and Extension Cohorts: Time to Response as Assessed by the Investigator and IRC

Time: Up to 36 months after first dose

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Measure: Part 2, Expansion Cohort 3: Duration of Intracranial Response (iDOR)

Time: up to 36 months after first dose

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Measure: Parts 2 and 3, Expansion and Extension Cohorts: Disease Control Rate (DCR) as Assessed by the Investigator and IRC

Time: Up to 36 months after first dose

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Measure: Parts 2 and 3, Expansion and Extension Cohorts: Progression Free Survival (PFS) as Assessed by the Investigator and IRC

Time: Up to 36 months after first dose

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Measure: Part 2, Expansion Cohort 3: Intracranial PFS (iPFS)

Time: up to 36 months after first dose

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Measure: Parts 2 and 3, Expansion and Extension Cohorts: Overall Survival (OS)

Time: Up to 36 months after first dose

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Measure: Part 2, Expansion Cohorts 6: Confirmed ORR as Assessed by the Investigator

Time: Up to 36 months after first dose

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Measure: Part 3, Extension Cohort: Confirmed ORR as Assessed by the Investigator

Time: Up to 36 months after first dose

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Measure: Part 3, Number of Participants With Patient-reported Symptoms (Lung Cancer), Functioning, and Health-related Quality of Life (HRQoL) Based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30)

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

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Measure: Part 3, Number of Participants With Patient-reported Symptoms (Lung Cancer), Functioning, and health-related Global Quality of Life (HRQoL) Based on Quality of Life Questionnaire Lung Cancer Module-13 (QLQ-LC13)

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

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