longkanker Non-small cell lung cancer
Conditions
Interventions
TAK-788 group (Arm A): TAK-788 160 mg QD with or without a low-fat meal 
Chemotherapy group (Arm B): Investigator*s choice of either:
• Pemetrexed/cisplatin: pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2), on 
Day 1 of a 21-day cycle.
• Pemetrexed/carboplatin: pemetrexed (500 mg/m2) plus carboplatin, at a dose 
calculated to produce an area under the curve (AUC) of 5 mg·min/mL, on Day 1 of 
a 21-day cycle. The same calculated AUC should be used for all carboplatin 
doses.
Pemetrexed/cisplatin or pemetrexed/carboplatin will be repeated every 3 weeks 
for 4 cycles then followed by maintenance treatment with pemetrexed (500 
mg/m2), on Day 1 of a 21-day cycle thereafter.
Sponsors
Millenium Pharmaceuticals
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: • Male or female adult patients (aged 18 years or older, or as defined per local regulations). • Histologically or cytologically confirmed nonsquamous cell locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) NSCLC. • A documented EGFR in-frame exon 20 insertion mutation sometimes referred to 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-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 tyrosine kinase inhibitors (ie, exon 19 del, L858R, T790M, L861Q, G719X, or S768I, where X is any other amino acid). • Adequate tumor tissue available, either from primary or metastatic sites, for central laboratory confirmation of EGFR in-frame exon 20 insertion mutation. Note: confirmation of central test positivity is not required before randomization. • At least 1 measurable lesion per RECIST version 1.1. Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. • Adequate organ and hematologic function, as determined by the following: -- 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). - 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). - Total serum bilirubin <=1.5 times the ULN (<=3.0 times the ULN for patients with Gilbert syndrome or if liver metastases are present). - Estimated creatinine clearance >=45 mL/min (calculated by using the Cockcroft-Gault equation). - Serum albumin >=2 g/dL. - Serum lipase <=1.5 times the ULN. - Serum amylase <=1.5 times the ULN unless the increased serum amylase is due to salivary isoenzymes. - Absolute neutrophil count >=1500/µL. - Platelets >=100,000/µL. - Hemoglobin >=9 g/dL. - Serum electrolytes within normal ranges (ie, calcium, magnesium, potassium, and sodium) based on local laboratory testing.
Exclusion criteria
Exclusion criteria: • 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. • 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. • Received a moderate or strong cytochrome P450 (CYP)3A inhibitor or moderate or strong CYP3A inducer within 10 days before randomization. • Had major surgery within 28 days before randomization. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed. • 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. • Have known active brain metastases (have either previously untreated intracranial central nervous system [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. • Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic). • Currently being treated with medications known to be associated with the development of torsades de pointes. • Currently have or have had a history of interstitial lung disease, radiation pneumonitis that required steroid treatment, or drug-related pneumonitis. • Have an ongoing or active infection including, but not limited to, the requirement for intravenous antibiotics, or a known history of HIV. Testing for HIV is not required in the absence of history. Note: Hepatitis B surface antigen-positive patients are allowed to enroll if hepatitis B virus DNA is below 1000 copies/mL in the plasma. Patients who are positive for anti-hepatitis C virus antibody can be enrolled but must not have detectable hepatitis C virus RNA in the plasma. • Received a live vaccine within 4 weeks before randomization per SmPCs for pemetrexed, cisplatin,and carboplatin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - To compare the efficacy of TAK-788 as first-line treatment with that of platinum-based chemotherapy in patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations, as evidenced by progression-free survival (PFS) as assessed by blinded independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. - To assess the safety and tolerability of TAK-788 in comparison with platinum-based chemotherapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| • To compare secondary measures of clinical efficacy of TAK-788 to that of platinum-based chemotherapy, as evidenced by confirmed objective response rate (ORR), time to response, duration of response, disease control rate (DCR) per IRC and the investigator, and overall survival (OS) per the investigator. • To compare patient-reported symptoms (particular core symptoms of lung cancer), functioning, and health related quality of life (HRQoL) with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the EORTC lung cancer module, QLQ LC13, in patients treated with TAK 788 compared with those treated with platinum-based chemotherapy. • To collect pharmacokinetics (PK) of TAK 788 and its active metabolites, AP32960 and AP32914, to contribute to population PK and exposure-response analyses (TAK-788 group only). | — |
Countries
Netherlands
Outcome results
None listed