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A Study of TAK-788 in Adults With Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02716116
Recruitment Status : Recruiting
First Posted : March 23, 2016
Last Update Posted : May 25, 2021
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:

This study is about a medicine called TAK-788, also known as mobocertinib, given to adults with non-small cell lung cancer.

The main aims of this study are to check if there are any side effects from TAK-788, to learn how TAK-788 is processed by the body, and to determine the best dose of TAK-788 to treat this condition.

Participants will take TAK-788 capsules with chemotherapy. Participants will continue to take TAK-788 unless they or their doctor decide they should stop this treatment.

Participants will take TAK-788 capsules with or without chemotherapy under antidiarrhea prevention to determine the safety of TAK-788 treatment.


Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: TAK-788 Drug: Pemetrexed Drug: Carboplatin Phase 1 Phase 2

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 (Part 1), including Part 1A (dose escalation combination component of TAK-788 in combination with Pemetrexed/Carboplatin) and Part 1B (TAK-788 monotherapy and TAK-788 in combination with pemetrexed/carboplatin with primary antidiarrhea prevention with loperamide.) and expansion phase (Part 2), followed by an extension phase (Part 3).

The objectives of the dose escalation phase (Part 1),dose escalation combination phase (Part 1A, only for selected sites in the United States) and Antidiarrhea Prophylaxis Cohorts ( part 1B, only for selected sites in the United States) are to determine the safety profile of orally administered TAK-788 and TAK-788 in combination with Pemetrexed/Carboplatin, including the MTD, DLTs, RP2D,pharmacokinetic profile and with loperamide as primary antidiarrhea prevention incidence and severity of TAK-788-associated diarrhea and anti-tumor activity of TAK-788 (Part 1B) . 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 395 participants.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 395 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 16, 2016
Estimated Primary Completion Date : March 30, 2022
Estimated Study Completion Date : March 13, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: Dose Escalation Component
TAK-788 treatment for participants with advanced NSCLC.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Experimental: Part 2: 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.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Experimental: Part 2: Expansion Cohort 2
TAK-788 treatment for NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Experimental: Part 2: 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.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Experimental: Part 2: 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.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Experimental: Part 2: 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.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Experimental: Part 2: 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
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Experimental: Part 2: 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.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Experimental: Part 3: Extension Cohort
TAK-788 treatment for participants with previously treated locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Experimental: Part 1A: Dose Escalation Combination Component
TAK-788 treatment in combination with pemetrexed/carboplatin for participants with NSCLC harboring EGFR exon 20 insertion mutation in approximately 3 dose levels. This cohort is only for participants at selected sites in the United States.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Drug: Pemetrexed
Pemetrexed intravenous infusion.

Drug: Carboplatin
Carboplatin intravenous infusion.

Experimental: Part 1B, Cohort 1: TAK 788 Antidiarrhea Prophylaxis, Monotherapy
TAK-788 monotherapy with primary antidiarrhea prophylaxis for participants with NSCLC with EGFR exon 20 activating insertions and who have no active, measurable CNS metastases. This cohort is only for participants at selected sites in the United States.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Drug: Pemetrexed
Pemetrexed intravenous infusion.

Drug: Carboplatin
Carboplatin intravenous infusion.

Experimental: Part 1B, Cohort 2: TAK 788 Antidiarrhea Prophylaxis, Combination Therapy
TAK-788 in combination with pemetrexed/carboplatin treatment with primary antidiarrhea prophylaxis for participants with NSCLC with EGFR exon 20 activating insertions and who have no active, measurable CNS metastases. This cohort is only for participants at selected sites in the United States.
Drug: TAK-788
TAK-788 capsules.
Other Name: AP32788

Drug: Pemetrexed
Pemetrexed intravenous infusion.

Drug: Carboplatin
Carboplatin intravenous infusion.




Primary Outcome Measures :
  1. Part 1, Dose Escalation Component: RP2D of Orally Administered TAK-788 [ Time Frame: Cycle 1 (Cycle length is equal to [=] 28 days) ]
  2. Part 1A, Dose Escalation Combination Component: RP2D/MTD of Orally Administered TAK 788 in Combination With Pemetrexed/ Carboplatin [ Time Frame: Up to Cycle 2 (Cycle length=21 days) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  3. Part 1A, Dose Escalation Combination Component: Identify DLTs of Orally Administered TAK 788 in Combination With Pemetrexed/ Carboplatin [ Time Frame: Up to Cycle 2 (Cycle length=21 days) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  4. Part 2, 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 ]
  5. Part 2, Expansion Cohort 3: Intracranial ORR (iORR) Assessed by Independent Review Committee (IRC) [ Time Frame: Up to 36 months after first dose ]
  6. Part 2, Expansion Cohort 6: Confirmed ORR Assessed by IRC [ Time Frame: Up to 36 months after first dose ]
  7. Part 3, Extension Cohort: Confirmed ORR Assessed by IRC [ Time Frame: Up to 36 months after first dose ]
  8. Part 1B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) of >= Grade 3 Diarrhea Occurring During the First 4 Cycles of TAK-788 Dosing [ Time Frame: Up to 4 Cycles (each cycle length is 28 days) ]
    This outcome measure for Part 1B (Antidiarrhea Prophylaxis Cohorts) is specific to only selected sites in the United States.


Secondary Outcome Measures :
  1. Parts 1, 1A, 1B and 2, Dose Escalation and Expansion Cohorts: Safety Analysis of TAK-788 and when TAK-788 Given in Combination With Pemetrexed/ Carboplatin Assessed by Adverse Events, Toxicity Grades, and Laboratory Test Results [ Time Frame: Up to 36 months after first dose ]
    This outcome measure for Part 1A and 1B (dose escalation combination component) is specific to only selected sites in the United States.

  2. Part 1, Dose Escalation Component: Identify DLTs and MTD of TAK-788 [ Time Frame: Cycle 1 (Cycle length=28 days) ]
  3. Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: Cmax; Maximum Observed Concentration of TAK-788 and its Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  4. Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of TAK-788 and its Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  5. Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: AUC 24; Area Under the Concentration-time Curve from Time Zero to 24 hours for TAK-788 and its Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  6. Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: AUCt: Area Under the Concentration-time Curve from Time Zero to Time t for TAK-788 and its Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  7. Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: RAC (Cmax): Accumulation Ratio Based on Cmax of TAK-788 and its Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  8. Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: RAC (AUC): Accumulation Ratio Based on AUC of TAK-788 and its Metabolites [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  9. Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: Cmax: Dose Proportionality for TAK-788 Exposure [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  10. Parts 1, 1A and 2, Dose Escalation and Expansion Cohorts: AUC: Dose Proportionality for TAK-788 Exposure [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2, and 21 days for Part 1A) ]
    This outcome measure for Part 1A (dose escalation combination component) is specific to only selected sites in the United States.

  11. Part 2, Expansion Cohorts 1, 2, 3, 4, 5, and 7: Confirmed ORR as Assessed by IRC [ Time Frame: Up to 36 months after first dose ]
  12. Part 2, Expansion Cohorts: Best Overall Response as Assessed by the Investigator and IRC [ Time Frame: Up to 36 months after first dose ]
  13. Part 2, Expansion Cohorts: Best Target Lesion Response as Assessed by the Investigator and IRC [ Time Frame: Up to 36 months after first dose ]
  14. Parts 2 and 3, Expansion and Extension Cohorts: Duration of Response as Assessed by the Investigator and IRC [ Time Frame: Up to 36 months after first dose ]
  15. Part 2 and 3, Expansion and Extension Cohorts: Time to Response as Assessed by the Investigator and IRC [ Time Frame: Up to 36 months after first dose ]
  16. Part 2, Expansion Cohort 3: Duration of Intracranial Response (iDOR) [ Time Frame: up to 36 months after first dose ]
  17. Parts 2 and 3, Expansion and Extension Cohorts: Disease Control Rate (DCR) as Assessed by the Investigator and IRC [ Time Frame: Up to 36 months after first dose ]
  18. Parts 2 and 3, Expansion and Extension Cohorts: Progression Free Survival (PFS) as Assessed by the Investigator and IRC [ Time Frame: Up to 36 months after first dose ]
  19. Part 2, Expansion Cohort 3: Intracranial PFS (iPFS) [ Time Frame: up to 36 months after first dose ]
  20. Parts 2 and 3, Expansion and Extension Cohorts: Overall Survival (OS) [ Time Frame: Up to 36 months after first dose ]
  21. Part 2, Expansion Cohorts 6: Confirmed ORR as Assessed by the Investigator [ Time Frame: Up to 36 months after first dose ]
  22. Part 3, Extension Cohort: Confirmed ORR as Assessed by the Investigator [ Time Frame: Up to 36 months after first dose ]
  23. Part 3, 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) ]
  24. Part 3, Extension Cohort: 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) ]
  25. Part 1B, Antidiarrhea Prophylaxis Cohorts: ORR Assessed by the Investigator [ Time Frame: Up to 36 months after first dose ]
    This outcome measure for Part 1B (Antidiarrhea Prophylaxis Cohorts) is specific to only selected sites in the United States.

  26. Part 1B, Antidiarrhea Prophylaxis Cohorts: DOR as Assessed by the Investigator [ Time Frame: Up to 36 months after first dose ]
    This outcome measure for Part 1B (Antidiarrhea Prophylaxis Cohorts) is specific to only selected sites in the United States.

  27. Part 1B, Antidiarrhea Prophylaxis Cohorts: PFS Assessed by the Investigator [ Time Frame: Up to 36 months after first dose ]
    This outcome measure for Part 1B (Antidiarrhea Prophylaxis Cohorts) is specific to only selected sites in the United States.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

General Inclusion Criteria all cohorts: dose escalation, antidiarrhea prophylaxis, dose escalation combination, expansion, and extension:

  1. Have histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic NSCLC disease (Stage IIIB or IV) or other solid tumors. 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.
  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 1A: Combination dose escalation cohorts

  1. Participants who have a documented EGFR activating mutation by a local test.
  2. Participants with an o EGFR exon 20 insertion, with or without prior anticancer treatments.

    o EGFR mutation other than exon 20 insertions, failed or not tolerated prior anticancer therapies.

  3. Prior EGFR TKIs are allowed for all participants.

Part 1B Cohort 1: Antidiarrhea prophylaxis, monotherapy

  1. Have a documented EGFR in-frame exon 20 insertion by a local test,including A763_Y764insFQEA, V769_D770insASV, D770_N771insNPG, D770_N771insSVD, H773_V774insNPH, or any other in-frame exon 20 insertion mutation. The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations.
  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 for all participants. Part 1B Cohort 2: Antidiarrhea prophylaxis, combination dose with chemotherapy
  1. Have a documented EGFR activating mutation by a local test,including exon 20 insertions, exon 19 deletions or exon 21 L858R substitution (with or without T790M), or an uncommon activating mutation including G719X (where X is any other amino acid), S768I, L861Q, or L861R, more specifically.
  2. Participants with an

    o EGFR exon 20 insertion, with or without prior anticancer treatments.

    o EGFR mutation other than exon 20 insertions, failed or not tolerated prior anticancer therapies.

  3. Prior EGFR TKIs are allowed for all participants.

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.

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. With an EGFR exon 20 insertion: 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.

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.

    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 (greater than or equal to [>=]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, and 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 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.

    o 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 criteria 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), Part 1A (dose escalation combination), Part 1B (antidiarrheal prophylaxis) 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.

    Part 1A: Combination dose escalation cohorts

    1. Have a history of or suspected severe hypersensitivity reaction to platinum-containing drugs, pemetrexed, or any known excipients of these drugs.
    2. Grade >2 peripheral neuropathy National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0).
    3. Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with evaluation of the study drug; this should include known contraindications mentioned in the United States prescribing information (USPIs) for pemetrexed, and carboplatin.
    4. Received a live vaccine within 4 weeks before randomization (per USPIs for pemetrexed and carboplatin).

    Part 1B Cohort 1: Antidiarrhea prophylaxis, monotherapy 1. In addition to the uncontrolled, or active cardiovascular disease, restrictions above; cardiac ejection fraction less than (<) 50% by echocardiogram or MUGA scan.

    Part 1B Cohort 2: Antidiarrhea prophylaxis, combination dose with chemotherapy

    1. Grade >2 peripheral neuropathy
    2. Received a live vaccine within 4 weeks before randomization (per USPIs for pemetrexed and carboplatin).
    3. In addition to the uncontrolled, or active cardiovascular disease, restrictions above; cardiac ejection fraction less than (<) 50% by echocardiogram or MUGA scan.

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): NCT02716116


Contacts
Layout table for location contacts
Contact: Takeda Contact +1-877-825-3327 medinfoUS@takeda.com

Locations
Show Show 69 study locations
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Takeda
Investigators
Layout table for investigator information
Study Director: Study Director Takeda
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02716116    
Other Study ID Numbers: AP32788-15-101
U1111-1217-7205 ( Registry Identifier: WHO )
2016-001271-68 ( EudraCT Number )
First Posted: March 23, 2016    Key Record Dates
Last Update Posted: May 25, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors