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A Trial of TAK-788 (AP32788) in Non-small Cell Lung Cancer (NSCLC)

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ClinicalTrials.gov Identifier: NCT02716116
Recruitment Status : Recruiting
First Posted : March 23, 2016
Last Update Posted : September 5, 2019
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE March 14, 2016
First Posted Date  ICMJE March 23, 2016
Last Update Posted Date September 5, 2019
Actual Study Start Date  ICMJE April 30, 2016
Estimated Primary Completion Date January 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 3, 2019)
  • Dose Escalation Cohort: RP2D of Orally Administered TAK-788 [ Time Frame: Day 1 to 28 (Cycle 1) ]
  • Expansion Cohorts 1, 2, 4, 5 and 7: Confirmed Objective Response Rate (ORR) Assessed by the Investigator [ Time Frame: up to 36 months after first dose ]
  • Expansion Cohort 3: Intracranial ORR (iORR) Assessed by Independent Review Committee (IRC) [ Time Frame: up to 36 months after first dose ]
  • Extension Cohort: Confirmed ORR Assessed by IRC [ Time Frame: up to 36 months after first dose ]
  • Expansion Cohort 6: Confirmed ORR Assessed by IRC [ Time Frame: up to 36 months after first dose ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 17, 2016)
  • Recommended Phase 2 Dose (RP2D) of orally administered AP32788 in the Dose Escalation Cohort [ Time Frame: Day 1 to 28 (Cycle 1) ]
    The RP2D will be the Maximum Tolerated Dose (MTD) or less. The MTD is defined as the highest dose at which ≤1 of 6 evaluable patients experience a dose-limiting toxicity (DLT) within the first 28 days of treatment. A DLT is a drug-related toxicity that is observed to occur within the first 28 days of treatment. Toxicity grades will be defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. 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.
  • Overall Response Rate (ORR) in the Expansion Cohorts [ Time Frame: up to 24 months after first dose ]
    For Expansion Cohorts 1, 2, and 4, ORR is defined as Investigator-assessed overall response rate (using Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]). For Expansion Cohort 3, ORR is defined as the intracranial overall response rate.
Change History Complete list of historical versions of study NCT02716116 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 3, 2019)
  • Dose Escalation and Expansion Cohorts: Safety Analysis of TAK-788 Assessed by Adverse Events, Toxicity Grades, and Laboratory Test Results [ Time Frame: up to 36 months after first dose ]
  • Dose Escalation Cohort: Identify DLTs and MTD of TAK-788 [ Time Frame: Day 1 to 28 in Cycle 1 (Cycle length is equal to [=] 28 days) ]
  • Dose Escalation and Expansion Cohorts: Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) of TAK-788 and its Active Metabolite [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days) ]
  • Dose Escalation and Expansion Cohorts: AUC(0-24): Area Under the Concentration-time Curve from Time Zero to 24 hours for TAK-788 and its Active Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days) ]
  • Dose Escalation and Expansion Cohorts: AUCt: Area Under the Concentration-time Curve from Time Zero to Time t for TAK-788 and its Active Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days) ]
  • Dose Escalation and Expansion Cohorts: RAC (Cmax): Accumulation Ratio Based on Cmax of TAK-788 and its Active Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days) ]
  • Dose Escalation and Expansion Cohorts: Ctrough: Observed Concentration at the end of a Dosing Interval of TAK-788 and its Active Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days) ]
  • Dose Escalation and Expansion Cohorts: RAC (AUC): Accumulation Ratio Based on AUC of TAK-788 and its Active Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days) ]
  • Dose Escalation and Expansion Cohorts: Cmax: Maximum Observed Concentration of TAK-788 and its Active Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days) ]
  • Expansion Cohorts 1, 2, 3, 4, 5, and 7: Confirmed ORR as Assessed by IRC [ Time Frame: up to 36 months after first dose ]
  • Expansion Cohorts: Best Overall Response as Assessed by the Investigator and IRC [ Time Frame: up to 36 months after first dose ]
  • Expansion Cohorts: Best Target Lesion Response as Assessed by the Investigator and IRC [ Time Frame: up to 36 months after first dose ]
  • Expansion and Extension Cohorts: Duration of Response as Assessed by the Investigator and IRC [ Time Frame: up to 36 months after first dose ]
  • Expansion and Extension Cohorts: Time to Response as Assessed by the Investigator and IRC [ Time Frame: up to 36 months after first dose ]
  • Expansion Cohort 3: Duration of Intracranial Response (iDOR) [ Time Frame: up to 36 months after first dose ]
  • Expansion and Extension Cohorts: Disease Control Rate (DCR) as Assessed by the Investigator and IRC [ Time Frame: up to 36 months after first dose ]
  • Expansion and Extension Cohorts: Progression Free Survival (PFS) as Assessed by the Investigator and IRC [ Time Frame: up to 36 months after first dose ]
  • Expansion Cohort 3: Intracranial PFS (iPFS) [ Time Frame: up to 36 months after first dose ]
  • Expansion and Extension Cohorts: Overall Survival (OS) [ Time Frame: up to 36 months after first dose ]
  • Extension Cohort: Confirmed ORR as Assessed by the Investigator [ Time Frame: up to 36 months after first dose ]
  • Dose Escalation and Expansion Cohorts: Cmax: Dose Linearity for TAK-788 Exposure [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days) ]
  • Dose Escalation and Expansion Cohorts: AUC: Dose Linearity for TAK-788 Exposure [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days) ]
  • 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 Frame: up to 30 days after last dose of drug (approximately up to 37 months) ]
  • 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 Frame: up to 30 days after last dose of drug (approximately up to 37 months) ]
  • Expansion Cohorts 6: Confirmed ORR as Assessed by the Investigator [ Time Frame: up to 36 months after first dose ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2016)
  • Safety Analysis of AP32788 Assessed by Adverse Events, Toxicity Grades, and Laboratory Test Results [ Time Frame: up to 24 months after first dose ]
    Rates of adverse events (AEs), and serious AEs (SAEs) graded according to the NCI CTCAE v4.0; the frequency of occurrence of overall toxicity, categorized by toxicity grades (severity); listings of laboratory test results will also be generated, and descriptive statistics summarizing the changes in laboratory tests over time will be analyzed.
  • Identify DLTs and MTD of AP32788 in the Dose Escalation Phase [ Time Frame: Day 1 to 28 (Cycle 1) ]
  • Maximum plasma concentration (Cmax) of AP32788 and its metabolites [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
  • Time to Cmax (Tmax) [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
  • Terminal half-life (t½λz) of AP32788 [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
  • Area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24) for AP32788 and its metabolites [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
  • Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t) of AP32788 and its metabolites [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
  • Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) of AP32788 and its metabolites [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
  • Apparent plasma clearance (CL/F) of AP32788 [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
  • Apparent volume of distribution (V/F) of AP32788 [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
  • Dose linearity for AP32788 exposure (Cmax and AUC) [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
  • The Accumulation Ratio of AP32788 (RAC) [ Time Frame: Up to 3 Cycles (each cycle 28 days) ]
    Extent of accumulation on multiple dosing
  • Overall response rate as assessed by Independent Review Committee [ Time Frame: up to 24 months after first dose ]
  • Best Overall Response [ Time Frame: up to 24 months after first dose ]
  • Best Target Lesion Response [ Time Frame: up to 24 months after first dose ]
  • Duration of Response [ Time Frame: up to 24 months after first dose ]
  • Duration of intracranial response in Expansion Cohort 3 [ Time Frame: up to 24 months after first dose ]
  • Disease Control Rate (DCR) [ Time Frame: up to 24 months after first dose ]
    The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)
  • Progression Free Survival (PFS) [ Time Frame: up to 24 months after first dose ]
  • Intracranial PFS in Expansion Cohort 3 [ Time Frame: up to 24 months after first dose ]
  • Overall Survival (OS) [ Time Frame: up to 24 months after first dose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of TAK-788 (AP32788) in Non-small Cell Lung Cancer (NSCLC)
Official Title  ICMJE A Phase 1/2 Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of the Oral EGFR/HER2 Inhibitor TAK-788 (AP32788) in Non-Small Cell Lung Cancer
Brief Summary The purpose of this phase 1/2 study is to evaluate the safety, recommended phase 2 dose (RP2D), dose limiting toxicities (DLTs), maximum tolerated dose (MTD), pharmacokinetics of oral TAK-788 and its active metabolites, anti-tumor activity of TAK-788 in participants with NSCLC with epidermal growth factor receptor (EGFR) or human epidermal growth factor 2 (HER2) mutations, and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations, and to explore relationship between tumor and/or plasma biomarkers, and TAK-788 efficacy, safety, and/or cytochrome P450 3A (CYP3A) induction. The study will also determine the efficacy of TAK-788 in participants with locally advanced or metastatic NSCLC harboring EGFR in-frame exon 20 insertion mutations who have received at least 1 prior line of therapy for locally advanced or metastatic NSCLC.
Detailed Description

This phase 1/2 study will evaluate the safety, pharmacokinetics, and anti-tumor activity of oral EGFR/HER2 Inhibitor TAK-788 in participants with NSCLC and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations. The trial will be conducted in three parts: a dose escalation and expansion phase, followed by an extension phase.

The objectives of the dose escalation phase are to determine the safety profile of orally administered TAK-788, including the MTD, DLTs, RP2D and pharmacokinetic profile. The primary goal of the expansion component of the trial is to evaluate the anti-tumor activity of TAK-788 in seven histologically and molecularly defined cohorts at the RP2D (determined based on dose escalation phase of the trial).

The seven expansion cohorts will be:

  1. NSCLC participants with EGFR exon 20 activating insertions, who have either not received or not shown an objective response to an EGFR TKI, and who have no active, measurable CNS metastases;
  2. NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases;
  3. NSCLC participants with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases;
  4. NSCLC participants with other targets against which TAK-788 is active (examples include EGFR exon 19 deletions or exon 21 substitutions [with or without T790M mutations] and other uncommon EGFR activating mutations), without active CNS metastases;
  5. NSCLC participants with EGFR exon 20 activating insertions, who have previously shown an objective response to an EGFR TKI and subsequently progressed, without active CNS metastases;
  6. NSCLC participants with EGFR exon 20 activating insertions, who have not received prior systemic anticancer treatment for locally advanced or metastatic disease, without active CNS metastases; and
  7. Participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active, without active CNS metastases.

The extension phase will evaluate efficacy of TAK-788 in participants with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations and who have been previously treated. The study will enroll approximately 341 participants.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788
Study Arms  ICMJE
  • Experimental: Dose Escalation Cohort
    TAK-788 treatment for participants with advanced NSCLC.
    Intervention: Drug: TAK-788
  • Experimental: Expansion Cohort 1
    TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions, who have either not received or not shown an objective response to an EGFR tyrosine kinase inhibitors (TKI), and who have no active, measurable central nervous system (CNS) metastases.
    Intervention: Drug: TAK-788
  • Experimental: Expansion Cohort 2
    TAK-788 treatment for NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases.
    Intervention: Drug: TAK-788
  • Experimental: Expansion Cohort 3
    TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases.
    Intervention: Drug: TAK-788
  • Experimental: Expansion Cohort 4
    TAK-788 treatment for NSCLC participants with other targets against which TAK-788 is active (examples include EGFR exon 19 deletions or exon 21 substitutions [with or without T790M mutations] and other uncommon EGFR activating mutations), without active CNS metastases.
    Intervention: Drug: TAK-788
  • Experimental: Expansion Cohort 5
    TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions, who have previously shown an objective response to an EGFR TKI and subsequently progressed without active CNS metastases.
    Intervention: Drug: TAK-788
  • Experimental: Expansion Cohort 6
    TAK-788 treatment NSCLC participants with EGFR exon 20 activating insertions, who have not received prior systemic anticancer treatment for locally advanced or metastatic disease without active CNS metastases
    Intervention: Drug: TAK-788
  • Experimental: Expansion Cohort 7
    TAK-788 treatment for participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active without active CNS metastases.
    Intervention: Drug: TAK-788
  • Experimental: Extension Cohort
    TAK-788 treatment for participants with previously treated locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations.
    Intervention: Drug: TAK-788
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2018)
341
Original Estimated Enrollment  ICMJE
 (submitted: March 17, 2016)
105
Estimated Study Completion Date  ICMJE January 28, 2021
Estimated Primary Completion Date January 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

General Inclusion Criteria (all cohorts: dose escalation, expansion and extension):

  1. Have histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic disease (Stage IIIB or IV). For all cohorts except Expansion Cohort 7, the locally advanced or metastatic disease is NSCLC. For Expansion Cohort 7, the locally advanced or metastatic disease is any solid tumor other than NSCLC.
  2. Must have sufficient tumor tissue available for analysis. For participants in the expansion cohorts and in the extension cohort, tumor tissue obtained after progression on the most recent prior therapy is preferred.
  3. Must have measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1.
  4. Male or female adult participants (aged 18 years or older, or as defined per local regulations).
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
  6. Minimum life expectancy of 3 months or more.
  7. Adequate organ function at baseline.
  8. Normal QT interval on screening electrocardiogram (ECG), defined as QT interval corrected (Fridericia) (QTcF) of less than or equal to (<=) 450 millisecond (ms) in males or <=470 ms in females.
  9. Willingness and ability to comply with scheduled visits and study procedures.

Part 1: Dose Escalation Cohort Specific Inclusion Criteria:

1. Refractory to standard available therapies.

Part 2: Expansion Cohort 1 Specific Inclusion Criteria:

  1. Have a documented EGFR in-frame exon 20 insertion by a local test.
  2. Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
  3. Prior treatment with an EGFR TKI is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI.

Expansion Cohort 2 Specific Inclusion Criteria:

  1. Have one of the following documented by a local test:

    1. A HER2 exon 20 insertion;
    2. An activating point mutation in HER2.
  2. Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
  3. Prior treatment with a pan-HER TKI (example, afatinib, neratinib, or dacomitinib) is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI.

Part 2: Expansion Cohort 3 Specific Inclusion Criteria:

  1. Have one of the following documented by a local test:

    1. An EGFR exon 20 insertion;
    2. A HER2 exon 20 insertion;
    3. An activating point mutation in HER2.
  2. Previously treated with one or more regimen of systemic therapy for locally advanced or metastatic disease.
  3. For participants with an EGFR exon 20 insertion: prior treatment with an EGFR TKI is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI.
  4. For participants with a HER2 exon 20 insertion or HER2 activating point mutation: prior treatment with a pan-HER TKI (example, afatinib, neratinib, or dacomitinib) is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI.
  5. Have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions.
  6. Have at least one target (that is, measurable) intracranial CNS lesion (>=10 millimeter [mm] in longest diameter by contrast enhanced magnetic resonance imaging [MRI]).

Part 2: Expansion Cohort 4 Specific Inclusion Criteria:

  1. Have one of the following documented by a local test: an activating mutation in EGFR including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or an uncommon activating mutation other than exon 20 insertion including, but not limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R.
  2. Treatment naive for locally advanced or metastatic disease or previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.

Part 2: Expansion Cohort 5 Specific Inclusion Criteria:

NSCLC participants with EGFR exon 20 activating insertions, who have previously shown an objective response to an EGFR TKI and subsequently progressed, without active CNS metastases.

  1. Have a documented EGFR in-frame exon 20 insertion by a local test.
  2. Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
  3. Previously showed an objective response to an EGFR TKI, then subsequently progressed as assessed by the investigator or treating physician.

Part 2: Expansion Cohort 6 Specific Inclusion Criteria:

NSCLC participants with EGFR exon 20 activating insertions, who have not received prior systemic anticancer treatment for locally advanced or metastatic disease, without active CNS metastases.

  1. Have a documented EGFR in-frame exon 20 insertion by a local test.
  2. No prior systemic treatment for locally advanced or metastatic disease.

Part 2: Expansion Cohort 7 Specific Inclusion Criteria:

Participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active, without active CNS metastases.

  1. Have a locally advanced or metastatic solid tumor that is not NSCLC, including, but not limited to, bladder/urinary tract cancer, breast cancer, gastric/esophageal cancer, biliary tract cancer, and head and neck cancer.
  2. Is refractory to standard therapy.
  3. Have EGFR or HER2 mutations, documented by a local test.

Part 3: Extension Cohort Specific Inclusion Criteria:

  1. Have a documented EGFR in-frame exon 20 insertion by a local test and sufficient tumor tissue available for central analysis.
  2. Must have received at least 1 prior line of therapy for locally advanced or metastatic disease and no more than 2 regimens of systemic anticancer chemotherapies for locally advanced or metastatic disease.

    • Prior treatment with an EGFR TKI is allowed unless the participant had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI.

Exclusion Criteria:

  1. Previously received TAK-788.
  2. Received small-molecule anticancer therapy (including cytotoxic chemotherapy, and investigational agents, <=14 days prior to first dose of TAK-788 (except for reversible EGFR TKIs [that is, erlotinib or gefitinib], which are allowed in the dose escalation and expansion cohorts up to 7 days prior to the first dose of TAK-788).
  3. Received antineoplastic monoclonal antibodies including immunotherapy within 28 days of the first dose of TAK-788.
  4. Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.

    Note: This exclusion criterion does not apply to Expansion Cohort 7.

  5. Received radiotherapy <=14 days prior to the first dose of TAK-788 or has not recovered from radiotherapy-related toxicities. Palliative radiation administered outside the chest and brain, stereotactic radiosurgery (SRS), and stereotactic body radiotherapy are allowed up to 7 days prior to the first dose
  6. Received a moderate or strong CYP4503A inhibitor or moderate or strong CYP3A inducer within 10 days prior to first dose of TAK-788.
  7. Have undergone major surgery within 28 days prior to first dose of TAK-788. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
  8. Part 1 (dose escalation) and Expansion Cohorts 1 to 3 of Part 2 (expansion phase) only:

    Have symptomatic CNS metastases at screening or asymptomatic disease requiring corticosteroids to control symptoms within 7 days prior to the first dose of TAK-788.

    Part 3 (extension cohort) and Expansion Cohorts 4 to 7 of Part 2 (expansion phase) only:

    Have known active brain metastases (have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions). Brain metastases are allowed if they have been treated with surgery and/or radiation and have been stable without requiring corticosteroids to control symptoms within 7 days before the first dose of TAK-788, and have no evidence of new or enlarging brain metastases.

  9. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
  10. Have significant, uncontrolled, or active cardiovascular disease.
  11. Have a known history of uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
  12. Have prolonged QTcF interval, or being treated with medications known to be associated with the development of Torsades de Pointes.
  13. Have an ongoing or active infection, including but not limited to, the requirement for intravenous (IV) antibiotics, or a known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Testing is not required in the absence of history.
  14. Currently have or have a history of interstitial lung disease, radiation pneumonitis that required steroid treatment, or drug-related pneumonitis.
  15. Female participants who are lactating and breastfeeding or have a positive urine or serum pregnancy test during the screening period.

    Note: Female participants who are lactating will be eligible if they discontinue breastfeeding.

  16. Have gastrointestinal illness or disorder that could affect oral absorption of TAK-788.
  17. Have any condition or illness that, in the opinion of the investigator, might compromise participant safety or interfere with the evaluation of the safety of the drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com
Listed Location Countries  ICMJE China,   France,   Germany,   Italy,   Korea, Republic of,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02716116
Other Study ID Numbers  ICMJE AP32788-15-101
U1111-1217-7205 ( Registry Identifier: WHO )
2016-001271-68 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Responsible Party Takeda ( Millennium Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Collaborators  ICMJE Takeda
Investigators  ICMJE Not Provided
PRS Account Takeda
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP