Clinical Trials /

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

NCT04129502

Description:

The purpose of this study is to compare the efficacy of TAK-788 as first-line treatment with that of platinum-based chemotherapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations
  • Official Title: A Randomized Phase 3 Multicenter Open-label Study to Compare the Efficacy of TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations

Clinical Trial IDs

  • ORG STUDY ID: TAK-788-3001
  • NCT ID: NCT04129502

Conditions

  • Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
TAK-788AP32788TAK-788 Group (Arm A)
PemetrexedPlatinum-based Chemotherapy Group (Arm B)
CisplatinPlatinum-based Chemotherapy Group (Arm B)
CarboplatinPlatinum-based Chemotherapy Group (Arm B)

Purpose

The purpose of this study is to compare the efficacy of TAK-788 as first-line treatment with that of platinum-based chemotherapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

Detailed Description

      The drug being tested in this study is called TAK-788. TAK-788 is being tested to evaluate
      the efficacy as a first line treatment compare with platinum-based chemotherapy in the
      participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose
      tumors harbor EGFR exon 20 insertion mutations.

      The study will enroll approximately 318 patients. Participants will be randomly assigned to
      one of the two treatment groups—

        -  TAK-788 group (Arm A)

        -  Platinum-based chemotherapy group (Arm B)

      The participants will be administered with TAK-788 orally in arm A and Pemetrexed/Cisplatin
      or Pemetrexed/Carboplatin intravenously (IV) in arm B until the participants experience
      progressive disease (PD) as assessed by blinded independent review committee (IRC),
      intolerable toxicity or another discontinuation criteria. Participants in the chemotherapy
      group may cross over to treatment with TAK-788 after IRC-assessed PD is documented.
      Randomized treatment with TAK-788 or platinum-based chemotherapy may be continued after PD,
      at the discretion of the investigator and with the sponsor's approval, if there is still
      evidence of clinical benefit.

      This multi-center trial will be conducted in United States, Europe, Asia and Latin America.
      The overall time to participate in this study is until 3 years after the last participant is
      randomized. Participants will make multiple visits to the clinic and will be followed for
      survival, subsequent anticancer therapy, subsequent disease assessment outcome until disease
      progression on a subsequent anticancer therapy, and participant-reported health status
      (EQ-5D-5L) for 3 years after the last participant is randomized in the study and 30 days
      after the last dose of study drug for safety follow-up.
    

Trial Arms

NameTypeDescriptionInterventions
TAK-788 Group (Arm A)ExperimentalTAK-788 160 mg, 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.
  • TAK-788
Platinum-based Chemotherapy Group (Arm B)Active ComparatorPemetrexed 500 mg/m^2 plus Cisplatin 75 mg/m^2, infusion, intravenously, once on Day 1 of 21-day cycle pemetrexed 500 mg/m^2 plus Carboplatin, infusion, intravenously, 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.
  • Pemetrexed
  • Cisplatin
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed locally advanced not suitable for definitive
             therapy, recurrent, or metastatic (Stage IV) non-small cell lung cancer (NSCLC)

          -  Documented epithelial growth factor receptor (EGFR) in-frame exon 20 insertion
             mutation assessed by a clinical laboratory improvements amendment (CLIA)-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 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)

          -  Adequate tumor tissue available, either from primary or metastatic sites, for central
             laboratory confirmation of EGFR exon 20 insertion mutation

          -  At least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST)
             version 1.1

          -  Life expectancy ≥3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

        Exclusion Criteria:

          -  Received prior systemic treatment for locally advanced or metastatic disease

          -  Received radiotherapy ≤14 days before randomization or has not recovered from
             radiotherapy-related toxicities

          -  Received a moderate or strong cytochrome P-450 (CYP)3A inhibitor or moderate or strong
             CYP3A inducer within 10 days before randomization

          -  Have been diagnosed with another primary malignancy other than NSCLC

          -  Have current spinal cord compression or leptomeningeal disease

          -  Have uncontrolled hypertension. Participants with hypertension should be under
             treatment on study entry to control blood pressure
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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 Measures

Measure: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
Safety Issue:
Description:Confirmed ORR is defined as the proportion 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.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 40 months after the first participant is randomized
Safety Issue:
Description:OS is defined as the interval from the date of randomization until death.
Measure:Progression Free Survival (PFS) as Assessed by the Investigator
Time Frame:Up to approximately 40 months after the first participant is randomized
Safety Issue:
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:Confirmed Objective Response Rate (ORR) as Assessed by the Investigator
Time Frame:Up to approximately 40 months after the first participant is randomized
Safety Issue:
Description:Confirmed ORR is defined as the proportion 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.
Measure: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
Safety Issue:
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: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
Safety Issue:
Description:Time to response is defined as the time interval from the date of randomization until the initial observation of CR or PR.
Measure: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
Safety Issue:
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 6 weeks) after the initiation of study drug.
Measure: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 Frame:Up to approximately 40 months after the first participant is randomized
Safety Issue:
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:Participant-reported Symptoms as Assessed by the European Organisation 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
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • Drug Therapy

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