Clinical Trials List
Protocol NumberAP32788-15-101
NCT Number(ClinicalTrials.gov Identfier)NCT02716116
Completed
2019-04-01 - 2023-12-07
Phase I/II
Terminated6
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
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
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
Millennium Pharmaceuticals, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 王馨儀 無
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Chien-Chung Lin Division of Thoracic Medicine
- Po-Lan Su Division of Thoracic Medicine
- Wu-Chou Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 陳焜結 Division of Thoracic Medicine
- YEN-HSIANG HUANG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
- Gee-chen Chang Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- JIN-YUAN SHIH Division of Thoracic Medicine
- 蔡子修 Division of General Internal Medicine
- 楊景堯 Division of General Internal Medicine
- Chong-Jen Yu Division of Thoracic Medicine
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- 廖唯昱 Division of General Internal Medicine
- YEN-TING LIN Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- 許嘉林 Division of General Internal Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 徐偉勛 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 王馨儀 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chen Chia-Hung Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
- 廖偉志 Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Non-Small Cell Lung Cancer
Objectives
Parts 1 and 2: Dose Escalation and Expansion Cohorts
The objectives of this study for the dose escalation and expansion cohorts are:
1. To determine the safety profile of orally administered TAK-788
2. To identify the RP2D, dose-limiting toxicities (DLTs), and the MTD of TAK-788
3. To determine the PK profile of TAK-788 and its active metabolites, AP32960 and
AP32914
4. To evaluate the anti-tumor activity of TAK-788 in NSCLC with EGFR or HER2
mutations
5. To explore relationships between tumor and/or plasma biomarkers and TAK-788
efficacy, safety, and/or CYP3A induction
6. To evaluate the anti-tumor activity of TAK-788 in patients with solid tumors other than
NSCLC with EGFR or HER2 mutations
Part 3: Extension Cohort
The objectives of the study for the extension cohort are:
Primary: To determine the efficacy of TAK-788, as evidenced by confirmed ORR, as assessed
by the IRC, in patients with locally advanced or metastatic NSCLC harboring EGFR in-frame
exon 20 insertion mutations and who have received at least 1 prior line of therapy for locally
advanced or metastatic NSCLC
Test Drug
TAK-788 (AP32788)
Active Ingredient
TAK-788 (AP32788)
Dosage Form
Capsule
Capsule
Capsule
Capsule
Capsule
Dosage
5
20
40
20
40
Endpoints
Part 1: Dose Escalation Cohorts
The primary endpoint of the dose escalation component of the study is the RP2D of orally
administered TAK-788.
Part 2: Expansion Cohorts
The primary endpoint of the expansion cohorts is the investigator-assessed ORR (using RECIST
v1.1), except for Expansion Cohort 3, in which iORR (as assessed by the IRC) will be the
primary endpoint.
Part 3: Extension Cohort
The primary endpoint of the extension cohort is confirmed ORR, as assessed by the IRC, per
RECIST v1.1.
The primary endpoint of the dose escalation component of the study is the RP2D of orally
administered TAK-788.
Part 2: Expansion Cohorts
The primary endpoint of the expansion cohorts is the investigator-assessed ORR (using RECIST
v1.1), except for Expansion Cohort 3, in which iORR (as assessed by the IRC) will be the
primary endpoint.
Part 3: Extension Cohort
The primary endpoint of the extension cohort is confirmed ORR, as assessed by the IRC, per
RECIST v1.1.
Inclution Criteria
General Inclusion Criteria all cohorts: dose escalation, antidiarrhea prophylaxis, dose escalation combination, expansion, and extension:
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.
Must have sufficient tumor tissue available for analysis.
Must have measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1.
Male or female adult participants (aged 18 years or older, or as defined per local regulations).
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
Minimum life expectancy of 3 months or more.
Adequate organ function at baseline.
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.
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
Participants who have a documented EGFR activating mutation by a local test.
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.
Prior EGFR TKIs are allowed for all participants.
Part 1B Cohort 1: Antidiarrhea prophylaxis, monotherapy
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.
Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
Prior treatment with an EGFR TKI is allowed for all participants. Part 1B Cohort 2: Antidiarrhea prophylaxis, combination dose with chemotherapy
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.
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.
Prior EGFR TKIs are allowed for all participants.
Part 2: Expansion Cohort 1 Specific Inclusion Criteria:
Have a documented EGFR in-frame exon 20 insertion by a local test.
Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
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:
Have one of the following documented by a local test:
A HER2 exon 20 insertion;
An activating point mutation in HER2.
Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
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:
An EGFR exon 20 insertion;
A HER2 exon 20 insertion;
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:
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.
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.
Have a documented EGFR in-frame exon 20 insertion by a local test.
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.
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.
Must have sufficient tumor tissue available for analysis.
Must have measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1.
Male or female adult participants (aged 18 years or older, or as defined per local regulations).
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
Minimum life expectancy of 3 months or more.
Adequate organ function at baseline.
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.
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
Participants who have a documented EGFR activating mutation by a local test.
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.
Prior EGFR TKIs are allowed for all participants.
Part 1B Cohort 1: Antidiarrhea prophylaxis, monotherapy
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.
Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
Prior treatment with an EGFR TKI is allowed for all participants. Part 1B Cohort 2: Antidiarrhea prophylaxis, combination dose with chemotherapy
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.
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.
Prior EGFR TKIs are allowed for all participants.
Part 2: Expansion Cohort 1 Specific Inclusion Criteria:
Have a documented EGFR in-frame exon 20 insertion by a local test.
Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
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:
Have one of the following documented by a local test:
A HER2 exon 20 insertion;
An activating point mutation in HER2.
Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
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:
An EGFR exon 20 insertion;
A HER2 exon 20 insertion;
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:
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.
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.
Have a documented EGFR in-frame exon 20 insertion by a local test.
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
Exclusion Criteria:
Previously received TAK-788.
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).
Received antineoplastic monoclonal antibodies including immunotherapy within 28 days of the first dose of TAK-788.
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
Have a history of or suspected severe hypersensitivity reaction to platinum-containing drugs, pemetrexed, or any known excipients of these drugs.
Grade >2 peripheral neuropathy National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0).
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.
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
Grade >2 peripheral neuropathy
Received a live vaccine within 4 weeks before randomization (per USPIs for pemetrexed and carboplatin).
In addition to the uncontrolled, or active cardiovascular disease, restrictions above; cardiac ejection fraction less than (<) 50% by echocardiogram or MUGA scan.
Previously received TAK-788.
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).
Received antineoplastic monoclonal antibodies including immunotherapy within 28 days of the first dose of TAK-788.
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
Have a history of or suspected severe hypersensitivity reaction to platinum-containing drugs, pemetrexed, or any known excipients of these drugs.
Grade >2 peripheral neuropathy National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0).
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.
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
Grade >2 peripheral neuropathy
Received a live vaccine within 4 weeks before randomization (per USPIs for pemetrexed and carboplatin).
In addition to the uncontrolled, or active cardiovascular disease, restrictions above; cardiac ejection fraction less than (<) 50% by echocardiogram or MUGA scan.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
91 participants
