This study will look at whether the study drug Tepotinib works to stop the re-growth of your lung cancer. The study drug will be used in combination with an approved lung cancer medication called osimertinib, which is an EGFR inhibitor. This is a Phase II study, which means that the study drug has already been tested in a small number of people in previous clinical research studies. Only patient who have progressed on first-line osimertinib due to MET amplification will be enrolled in the study
- Conditions
- ocally advanced or metastatic NSCLC histology (confirmed by either histology or cytology) with documented activating mutation of the EGFR receptor including T790M statusResistance on previous first line osimertinibTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001538-33-DE
- Lead Sponsor
- Merck Healthcare KGaA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 122
1. Are = 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18
years of age [ie, = 20 years of age in Japan]), at the time of signing the informed consent.
2. Are participants with the following:
a) Locally advanced or metastatic NSCLC histology (confirmed by either histology or cytology) with documented activating EGFR mutation of the EGFR receptor including T790M status
b) Presence of at least 1 independently verified measurable lesion in accordance with RECIST 1.1, that can be accurately assessed at baseline with = 10 mm in the longest diameter (except lymph nodes which must Have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), which is suitable for accurate repeated measurements and that preferably was not previously irradiated or biopsied
c) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum life expectancy of 12 weeks
d) Acquired resistance on previous first-line-osimertinib. Participants must meet both of the following 2 criteria:
-Radiological documentation of disease progression on first-line-osimertinib.
- Objective clinical benefit documented during previous osimertinib therapy, defined by either partial or complete radiological response, or
durable stable disease (SD) (SD should last > 6 months) after initiation of osimertinib
e) Have received only first line osimertinib as a prior line of therapy in the noncurative advanced or metastatic NSCLC setting
f) MET amplification as determined by either FISH testing (central or local) on tumor tissue (TBx) or central blood-based next generation
sequencing (LBx). Tumor and blood samples must be collected following progression on prior first-line osimertinib at Prescreening.
-Submission of tumor tissue and blood sample obtained after progression on first line osimertinib, is mandatory for all patients for
MET amplification testing.
-Submission of tumor tissue during Prescreening or Screening is mandatory for patients with tumor tissue tested by local FISH, to
confirm MET amplification status. Central confirmation is not mandated prior to the start of study treatment
3.Woman no WOBCP, or, use a highly effective contraception. Man: Contraception or no intercourse with a WOBCP1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
1. Spinal cord compression or brain metastasis unless asymptomatic, stable or not requiring steroids for at least 2 weeks prior to start of study intervention. Prior radiotherapy or surgery for brain metastases such as stereotactic radiosurgery/gammaknife must have been completed = 2 weeks, all others = 4 weeks prior to start of therapy. Participants with leptomeningeal disease are ineligible.
2. Any unresolved toxicity Grade 2 or more according to NCI-CTCAE version 5, from previous anticancer therapy with the exception of alopecia.
3. Need for transfusion within 14 days prior to the first dose of study intervention.
4. Participants who have brain metastasis as the only measurable lesion
5. Inadequate hematological function:
? Hemoglobin < 8.5 g/dL
? Neutrophils < 1.5 × 109/L
? Platelets < 100 × 109/L.
6. Inadequate liver function:
? Total bilirubin > 1.5 × ULN
? AST/ALT/ALP > 3 × ULN
? For participants with liver metastases:
i. Total bilirubin > 1.5 × ULN
ii. AST/ALT/ALP > 5 × ULN
iii. For participants with bone metastases: ALP > 5 × ULN.
7. Inadequate renal function:
? Renal impairment as evidenced by serum creatinine ? 1.5 × ULN, or creatinine clearance (CrCl) < 30 mL/min calculated by the Cockcroft-Gault formula (24-hour CrCl might be requested by the Investigator for confirmation, if calculated CrCl is < 50 mL/min. In such case, participants with 24-hour CrCl < 30 mL/min should be excluded).
CrCl (mL/min) = [(140 – age(year)) × weight(kg)] 72 × serum creatinine (mg/dL) {× 0.85 for females}
8. History of ILD or interstitial pneumonitis including radiation pneumonitis that required steroid treatment.
9. Impaired cardiac function:
? Left ventricular ejection fraction < 45% defined by echocardiography
Grade 4 arrhythmia (NCI-CTCAE v5.0)
?? Unstable angina pectoris
? Congestive Heart Failure New York Heart Association III and IV
? Myocardial infarction, stroke, or transient ischemic attack within the last 6 months prior to study entry.
10. Corrected QT interval by Fredericia (QTcF) > 470 ms for women and > 450 ms for men at screening.
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes.
11. Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg).
12. Contraindication to the administration of osimertinib.
13. Medical history of liver fibrosis/cirrhosis.
14. Past or current history of neoplasm other than NSCLC, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, benign prostate neoplasm/hypertropia or other cancer curatively treated and with no evidence of disease for at least 5 years.
15. Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product.
16. Major surgery within 28 days prior to Day 1 of study intervention.
17. Known human immunodeficiency virus positivity.
18. Known hypersensitivity to any of the study intervention ingredients.
19. Has not received an EGFR-TKI containing treatment directly prior to enrollment into the study, ie, chemotherapy or checkpoint inhibitor treatment with/without vascular endothelial growth factor inhibitors either in monotherapy or in co
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