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.
- Conditions
- Locally advanced or metastatic NSCLC histology (confirmed by either histology or cytology) with documented activating mutation of the EGFR receptor including T790M status Resistance on previous EGFR-TKI therapyTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001538-33-ES
- Lead Sponsor
- Merck Healthcare KGaA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 90
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 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 EGFR-TKI therapy. Participants must meet both of the following 2 criteria:
-Radiological documentation of disease progression to previous EGFR-TKI therapy. Participants having received 2 or more previous EGFR-TKI containing therapies with/without vascular endothelial growth factor inhibitors need to show disease progression against 3rd generation EGFR-TKI, eg, osimertinib treatment
-At least 1 prior objective clinical benefit documented, defined by either partial or complete radiological response, or durable stable disease (SD) (SD should last > 6 months) after initiation of previous EGFR-TKI treatment(s)
e) Received at least 1 but no more than 4 prior lines of prior therapy in the noncurative advanced or metastatic NSCLC setting
f) MET amplification in plasma defined by a positive LBx test, using validated assays with an adequate regulatory status as determined by the Sponsor
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 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45
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.
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
? Serious arrhythmia
? 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 (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, 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 da
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