A Randomized Phase 3 Multicenter Open-label Study to Compare the Efficacy of TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations
- Conditions
- 10038666longkankerNon-small cell lung cancer
- Registration Number
- NL-OMON54828
- Lead Sponsor
- Millenium Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
• 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.
• 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- To compare the efficacy of TAK-788 as first-line treatment with that of<br /><br>platinum-based chemotherapy in patients with locally advanced or metastatic<br /><br>NSCLC whose tumors harbor EGFR exon 20 insertion mutations, as evidenced by<br /><br>progression-free survival (PFS) as assessed by blinded independent review<br /><br>committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST)<br /><br>version 1.1.<br /><br>- To assess the safety and tolerability of TAK-788 in comparison with<br /><br>platinum-based chemotherapy.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• To compare secondary measures of clinical efficacy of TAK-788 to that of<br /><br>platinum-based chemotherapy, as evidenced by confirmed objective response rate<br /><br>(ORR), time to response, duration of response, disease control rate (DCR) per<br /><br>IRC and the investigator, and overall survival (OS) per the investigator.<br /><br>• To compare patient-reported symptoms (particular core symptoms of lung<br /><br>cancer), functioning, and health related quality of life (HRQoL) with the<br /><br>European Organisation for Research and Treatment of Cancer (EORTC) Quality of<br /><br>Life Questionnaire (QLQ)-C30 and the EORTC lung cancer module, QLQ LC13, in<br /><br>patients treated with TAK 788 compared with those treated with platinum-based<br /><br>chemotherapy.<br /><br>• To collect pharmacokinetics (PK) of TAK 788 and its active metabolites,<br /><br>AP32960 and AP32914, to contribute to population PK and exposure-response<br /><br>analyses (TAK-788 group only).</p><br>