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

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ClinicalTrials.gov Identifier: NCT04129502
Recruitment Status : Not yet recruiting
First Posted : October 16, 2019
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC) Drug: TAK-788 Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 318 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : November 15, 2019
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : November 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: TAK-788 Group (Arm A)
TAK-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.
Drug: TAK-788
TAK-788 capsule
Other Name: AP32788

Active Comparator: Platinum-based Chemotherapy Group (Arm B)
Pemetrexed 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.
Drug: Pemetrexed
Pemetrexed IV infusion

Drug: Cisplatin
Cisplatin IV infusion

Drug: Carboplatin
Carboplatin IV infusion




Primary Outcome Measures :
  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 Measures :
  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 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.

  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 progressive disease (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 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.

  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 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 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 ]
    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 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 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04129502


Contacts
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Contact: Takeda Study Registration Call Center 877-825-3327 ext +1 medicalinformation@tpna.com

Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Millennium Pharmaceuticals, Inc.

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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04129502     History of Changes
Other Study ID Numbers: TAK-788-3001
First Posted: October 16, 2019    Key Record Dates
Last Update Posted: October 28, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cisplatin
Carboplatin
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors