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: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001845-42-ES
• Lead Sponsor: Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals is a wholly owned subsidiary of Takeda Pharmaceutical

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-01-10
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 318

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 locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) NSCLC.
3. A documented EGFR in-frame exon 20 insertion mutation (including A763_Y764insFQEA, V769_D770insASV, D770_N771insNPG, D770_N771insSVD, H773_V774insNPH, 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 D). 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 E).
8. Adequate organ and hematologic function, as determined by the following:
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) [35].
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.
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.f), from the time of signing the informed consent through 30 days after the last dose of study drug if they are randomized to the TAK-788 group or to practice the guidelines in the approved product labels for chemotherapy through 180 days after the last dose of pemetrexed if they are randomized to the chemotherapy group, 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 contracepti

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 (with the exception 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 F) 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. 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 randomization 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, 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) History of clinically significant (as determined by the treating physician) atrial arrhythmia.
e) Any history of ventricular arrhythmia.
f) 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 G).
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 history.
Note: Hepatitis B surface antigen (HBsAg)-posi

Study & Design

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