TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy for NSCLC With EGFR Exon 20 Insertions

Phase 1

Conditions: on-Small Cell Lung Cancer (NSCLC) with EGFR exon 20 insertion mutations
MedDRA version: 21.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2019-001845-42-BE

Lead Sponsor: Takeda Development Center Americas, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 354

Inclusion Criteria

Each patient must meet all the following inclusion criteria to be randomized to treatment:
1. Male or female adult patients (aged 18 years or older, or as defined per local regulations)
2. Histologically or cytologically confirmed nonsquamous cell locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) NSCLC
3. A documented EGFR in-frame exon 20 insertion mutation sometimes reffered as duplication (including A763_Y764insFQEA, V769_D770insASV [ASV duplication], D770_N771insNPG, D770_N771insSVD [SVD duplication], H773_V774insNPH [NPH duplication], or any other in-frame exon 20 insertion mutation) assessed by a Clinical Laboratory Improvements Amendment (CLIA)-certified (United States [US] sites) or an accredited (outside of the US) local laboratory. The local molecular testing reports may be required by the sponsor to confirm the exon 20 insertion mutation status. The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations except EGFR mutations for which there are approved EGFR TKIs (ie, exon 19 del, L858R, T790M, L861Q, G719X, or S768I, where X is any other amino acid)
4. Adequate tumor tissue available, either from primary or metastatic sites, for central laboratory confirmation of EGFR in-frame exon 20 insertion mutation (see laboratory manual). Note: Confirmation of central test positivity is not required before randomization
5. At least 1 measurable lesion per RECIST Version 1.1 (Appendix H). Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy
6. Life expectancy =3 months
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Appendix K)
8. Adequate organ and hematologic function, as determined by the following (listed criteria. Blood transfusions are permitted with a recommended =14 day washout period before blood samples are obtained for Cycle 1 Day 1 laboratory evaluations). This washout period may be shortened if deemed medically necessary by the principal investigator (but it must not be <7 days):
a) Alanine aminotransferase/aspartate aminotransferase =2.5 times the upper limit of the normal range (ULN; =5 times the ULN is acceptable if liver metastases are present)
b) Total serum bilirubin =1.5 times the ULN (=3.0 times the ULN for patients with Gilbert syndrome or if liver metastases are present)
c) Estimated creatinine clearance =45 mL/min (calculated by using the Cockcroft-Gault equation) (Cockcroft and Gault 1976)
d) Serum albumin =2 g/dL
e) Serum lipase =1.5 times the ULN
f) Serum amylase =1.5 times the ULN unless the increased serum amylase is due to salivary isoenzymes
g) Absolute neutrophil count =1500/µL
h) Platelets =100,000/µL
i) Hemoglobin =9 g/dL
j) Serum electrolytes within normal ranges (ie, calcium, magnesium, potassium, and sodium) based on local laboratory testing.
9. Normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of =450 milliseconds in males or =470 milliseconds in females
10. 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 (Table 8.j), from the time of signing the informed consent through 30 days after the last dose of stu

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be
randomized to treatment.
1. Female patients who are lactating and breastfeeding or have a positive urine or serum pregnancy test during the screening period.
Note: Female patients who are lactating will be eligible if they discontinue breastfeeding.
2. Current treatment in another therapeutic clinical study.
3. Received prior systemic treatment for locally advanced or metastatic disease, including local administration, such as intra-pleural injection of anticancer medication, with the exception noted below:
Neoadjuvant or adjuvant chemotherapy/immune therapy for Stage I to III or combined modality chemotherapy/radiation for locally advanced disease is allowed if completed >6 months before the development of metastatic disease.
4. Received radiotherapy =14 days before randomization or has not recovered from radiotherapy-related toxicities. Palliative radiation
administered outside the chest and brain, stereotactic radiosurgery, and stereotactic body radiotherapy are allowed up to 7 days before
randomization.
5. Received a moderate or strong cytochrome P-450 (CYP)3A inhibitor or moderate or strong CYP3A inducer (Appendix L) within 10 days before
randomization.
6. Had major surgery within 28 days before randomization. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
7. Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or
cervical cancer in situ; definitively treated nonmetastatic 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.
8. Symptomatic brain metastasis that has not been treated. (If they have been treated with surgery and/or radiation and have been stable
without requiring corticosteroids to control symptoms within 7 days before randomization and have no evidence of new or enlarging brain
metastases they are allowed to be randomized in the study).
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, specifically including, but not restricted to:
a) Myocardial infarction within 6 months before randomization.
b) Unstable angina within 6 months before randomization.
c) Congestive heart failure within 6 months before randomization.
d) Cardiac ejection fraction <50% by echocardiogram or multigated
acquisition (MUGA) scan.
e) History of clinically significant (as determined by the treating
physician) atrial arrhythmia.
f) Any history of ventricular arrhythmia.
g) Cerebrovascular accident or transient ischemic attack within 6 months before randomization.
11. Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure.
12. Currently being treated with medications known to be associated with the development of torsades de pointes (Appendix M).
13. Currently have or have had a history of interstitial lung disease, radiation pneumonitis that required steroid treatment, or drug-related pneumonitis.
14. Have an ongoing or active infection including, but not limited to, the requirement for IV antibiotics, or a known history of HIV. Testing for HIV
is not required in the absence of histor

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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