TAK-788 (AP32788) in Patients With Non-Small Cell Lung Cancer

Phase 1

• Conditions: on-Small Cell Lung Cancer (NSCLSC); MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: LLT Classification code 10025054 Term: Lung cancer non-small cell stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-001271-68-ES
• Lead Sponsor: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-11
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 91

Inclusion Criteria

General
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.
2.Must have sufficient tumor tissue available for analysis (see Study Reference Manual for specific requirements). For patients 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 RECIST v1.1 (Appendix B).
4.Male or female patients =18 years old. For patients in Japan, aged =20 years.
5.Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (Appendix A).
6.Minimum life expectancy of 3 months or more.
7.Adequate renal and hepatic function as defined by the following criteria:
a.Total serum bilirubin =1.5 × upper limit of normal (ULN) (=3.0 × ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy);
b.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 × ULN (or =5 × ULN if liver function abnormalities are due to underlying malignancy);
c.Estimated creatinine clearance =30 mL/min (calculated by using the Cockcroft-Gault equation);
d.Serum albumin =2 g/dL; and
e.Serum lipase/amylase =1.5 × ULN.
8.Adequate bone marrow function as defined by the following criteria:
a.Absolute neutrophil count (ANC) =1.5 × 109/L;
b.Platelet count =75 × 109/L; and
c.Hemoglobin =9.0 g/dL.
9.Normal QT interval on screening electrocardiogram (ECG), defined as QTcF of =450 ms in males or =470 ms in females.
10.All toxicities from prior therapy have resolved to = grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0 [18]), or have resolved to baseline, at the time of first dose of TAK 788. Note: treatment-related grade >1 alopecia or treatment-related grade 2 peripheral neuropathy are allowed if deemed irreversible.
11.Female patients who:
•Are postmenopausal for at least 1 year before the screening visit, OR
•Are surgically sterile, OR
•If they are of childbearing potential, agree to practice 1 highly effective, nonhormonal method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, OR
•Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
Male patients, even if surgically sterilized (ie, status postvasectomy), who:
•Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, OR
•Agree to practic

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 [ie, erlotinib or gefitinib], which are allowed 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 patients 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. SRS, stereotactic body radiotherapy, and palliative radiation outside the chest and brain are allowed up to 7 days prior to the first dose.
6.Received a strong CYP3A inhibitor or strong CYP3A inducer within 2 weeks prior to first dose of TAK 788 (see Appendix C).
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.Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring corticosteroids to control symptoms within 7 days prior to the first dose of TAK 788.
Note: If a patient has worsening neurological symptoms or signs due to CNS metastases, the patient needs to complete local therapy and be neurologically stable (with no requirement for corticosteroids or use of anticonvulsants) for 7 days prior to the first dose of TAK-788. Patients with no prior history of signs or symptoms of CNS metastases but who receive prophylactic steroids or anticonvulsants are allowed.
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, including, but not restricted to:
a.Myocardial infarction (MI) within 6 months prior to the first dose of study drug;
b.Unstable angina within 6 months prior to first dose;
c.Congestive heart failure (CHF) within 6 months prior to first dose;
d.History of clinically significant (as determined by the treating physician) atrial arrhythmia;
e.Any history of ventricular arrhythmia; or
f.Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose.
11.Have a known history of uncontrolled hypertension. Patients 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 (Appendix D).
13.(Parts 1 and 2 [dose escalation and expansion cohorts] only) Have an ongoing or active infection including, but not limited to, the requirement for intravenous (I

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified