TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations

JRCT ID: jRCT2071210098

Registered date:12/12/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)
• Date of first enrollment: 10/01/2020
• Target sample size: 354
• Countries of recruitment: Australia,Japan,Austria,Japan,Belgium,Japan,Canada,Japan,China,Japan,France,Japan,Germany,Japan,Greece,Japan,Hong Kong,Japan,Israel,Japan,Italy,Japan,Republic of Korea,Japan,Netherlands,Japan,Portugal,Japan,Russian Federation,Japan,Singapore,Japan,Spain,Japan,Sweden,Japan,Taiwan,Japan,Turkey,Japan,Ukraine,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

TAK-788 Group (Arm A)
TAK-788 160 mg with or without food, capsules, orally, once daily until the participants experience progressive disease (PD) as assessed by blinded independent review committee (IRC), intolerable toxicity, or another discontinuation criteria.

Platinum-based Chemotherapy Group (Arm B)
Pemetrexed 500 mg/m^2 plus cisplatin 75 mg/m^2, infusion, intravenously(IV), once on Day 1 of 21-day cycle pemetrexed 500 mg/m^2 plus Carboplatin, infusion, IV, once at a dose calculated to produce area under curve (AUC) of 5 mg*min/mL on Day 1 of 21-day cycle until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria. Pemetrexed/ cisplatin or pemetrexed/ carboplatin will be repeated every 3 weeks for 4 cycles, followed by maintenance treatment with pemetrexed 500 mg/m^2, on Day 1 of a 21-day cycle thereafter.

Outcome(s)

Primary Outcome

1.Progression Free Survival (PFS) as Assessed by Blinded Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame: Up to approximately 40 months after the first participant is randomized
PFS is defined as the time interval from the date of randomization until the first date at which the criteria for PD according to RECIST Version 1.1 are met or death, whichever occurs first.

Secondary Outcome

1.Confirmed Objective Response Rate (ORR) as Assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1
Time Frame: Up to approximately 40 months after the first participant is randomized
Confirmed ORR is defined as the percentage of participants who are confirmed to have achieved complete response (CR) or partial response (PR). Confirmed responses are responses that persist on repeat imaging >=4 weeks after initial response.

2.Overall Survival (OS)
Time Frame: Up to approximately 40 months after the first participant is randomized
OS is defined as the interval from the date of randomization until death.

3.Progression Free Survival (PFS) as Assessed by the Investigator
Time Frame: Up to approximately 40 months after the first participant is randomized
PFS is defined as the time interval from the date of randomization until the first date at which the criteria for PD according to RECIST Version 1.1 are met or death, whichever occurs first.

4.Confirmed Objective Response Rate (ORR) as Assessed by the Investigator
Time Frame: Up to approximately 40 months after the first participant is randomized
Confirmed ORR is defined as the percentage of participants who are confirmed to have achieved CR or PR. Confirmed responses are responses that persist on repeat imaging >=4 weeks after initial response.

5.Duration of Response, as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
Time Frame: Up to approximately 40 months after the first participant is randomized
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 or death (whichever occurs first) is objectively documented.

6.Time to Response, as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
Time Frame: Up to approximately 40 months after the first participant is randomized
Time to response is defined as the time interval from the date of randomization until the initial observation of CR or PR.

7.Disease Control Rate (DCR) as Assessed by the Blinded Independent Review Committee (IRC) and the Investigator
Time Frame: Up to approximately 40 months after the first participant is randomized
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 6 weeks) after the initiation of study drug.

8.Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
Time Frame: Up to approximately 40 months after the first participant is randomized
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).

9.Participant-reported Symptoms as Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire, Lung Cancer Module (QLQ-LC13)
Time Frame: Up to approximately 40 months after the first participant is randomized
EORTC QLQ-LC13 is a cancer-specific questionnaire which comprises of 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Raw scores will be converted into scale scores ranging from 0 to 100. Higher scores represent a high level of symptomatology/problems.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Male or female adult patients (aged 18 years or older)
2.Histologically or cytologically confirmed nonsquamous cell locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) NSCLC
3.Documented epidermal growth factor receptor (EGFR) in-frame exon 20 insertion mutation assessed by a clinical laboratory improvements amendment-certified (United States [US] sites) or an accredited (outside of the US) local laboratory The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or human epidermal growth factor receptor 2 (HER2) mutations except EGFR mutations for which there are approved anti-EGFR TKIs (ie, exon 19 del, L858R, T790M, L861Q, G719X, or S768I, where X is any other amino acid)
4.Adequate tumor tissue available, either from primary or metastatic sites, for central laboratory confirmation of EGFR exon 20 insertion mutation
5.At least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) Version 1.1
6.Life expectancy >=3 months
7.Eastern Cooperative Oncology Group performance status of 0 to 1
8.Adequate organ and hematologic function as defined by blood transfusions with a recommended >/ 14 day washout period.

Exclude criteria

1.Received prior systemic treatment for locally advanced or metastatic disease, including local administration, such as intra-pleural injection of anticancer medication with the exception noted below:
- Neoadjuvant or adjuvant chemotherapy/immune therapy for Stage I to III or combined modality chemotherapy/radiation for locally advanced disease is allowed if completed >6 months before the development of metastatic disease.
2.Received radiotherapy =<14 days before randomization or has not recovered from radiotherapy-related toxicities
3.Received a moderate or strong cytochrome P450 (CYP)3A inhibitor or moderate or strong CYP3A inducer within 10 days before first dose of TAK-788
4.Have been diagnosed with another primary malignancy other than NSCLC
5.Have current spinal cord compression or leptomeningeal disease
6.Have uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure
7.Received a live vaccine within 4 weeks before randomization per Summary of product characteristics (SmPCs) for pemetrexed, cisplatin, and carboplatin.
8.Taking medication(s) known to be associated with the development of torsades de pointes.

Related Information

• Primary Sponsor: Asato Takayuki
• Secondary ID(s): NCT04129502,U1111-1232-6059,2019-001845-42