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Report for Clinical Trial NCT03807778

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 1/2 Study of the Oral EGFR/HER2 Inhibitor TAK-788 in Japanese Non-Small Cell Lung Cancer Patients

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.

NCT03807778 Non-Small Cell Lung Cancer
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

1 Interventions

Name: TAK-788

Description: TAK-788 capsule
Type: Drug
Group Labels: 2

TAK-788, Phase 1 Part TAK-788, Phase 2 Part


Primary Outcomes

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 days

Description: 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 years

Secondary Outcomes

Description: 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 years

Description: 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 years

Description: 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 days

Description: 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 days

Measure: Phase 1 Part: Cmax: Maximum Plasma Concentration for TAK-788 and its Active Metabolites after a Single Oral Dose

Time: Up to 24 hours; Pre-dose and multiple time points post-dose on Cycle 1 Day 1 (C1D1)

Measure: Phase 1 Part: Tmax: Time to Cmax for TAK-788 and its Active Metabolites after a Single Oral Dose

Time: Up to 24 hours; Pre-dose and multiple time points post-dose on C1D1

Measure: Phase 1 Part: AUC24: Area Under the Plasma Concentration-Time Curve from Time 0 to 24 hours for TAK-788 and its Active Metabolites after a Single Oral Dose

Time: Up to 24 hours; Pre-dose and multiple time points post-dose on C1D1

Measure: Phase 1 Part: AUClast: Area Under the Plasma Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration for TAK-788 and its Active Metabolites after a Single Oral Dose

Time: Up to 24 hours; Pre-dose and multiple time points post-dose on C1D1

Measure: Phase 1 Part: Cmax, ss: Maximum Plasma Concentration for TAK-788 and its Active Metabolites at Steady State after Multiple Oral Doses

Time: Up to approximately 57 days; Pre-dose and multiple time points post-dose

Measure: Phase 1 Part: Tmax, ss: Time to Cmax for TAK-788 and its Active Metabolites at Steady State after Multiple Oral Doses

Time: Up to approximately 57 days; Pre-dose and multiple time points post-dose

Measure: Phase 1 Part: AUC24, ss: Area Under the Plasma Concentration-Time Curve from Time 0 to 24 hours for TAK-788 and its Active Metabolites at Steady State after Multiple Oral Doses

Time: Up to approximately 57 days; Pre-dose and multiple time points post-dose

Measure: Phase 1 Part: Rac: Extent of Accumulation Ratio on Multiple Dosing for TAK-788 and its Active Metabolites at Steady State after Multiple Oral Doses

Time: Up to approximately 57 days; Pre-dose and multiple time points post-dose

Description: 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 years

Description: 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 years

Description: 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 years

Description: 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 years

Description: 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 years

Description: 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 years

Description: 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 years

Description: 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 years

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 L858R

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 ---



HPO Nodes


HPO: