A Phase II, two arm study to investigate tepotinib combined with osimertinib in MET amplified, advanced or metastatic non-small cell lung cancer (NSCLC) harboring activating EGFR mutations and having acquired resistance to prior osimertinib therapy (INSIGHT 2 Study)
- Conditions
- locally advanced or metastic non-small cell lung carcinomalung cancer10038666
- Registration Number
- NL-OMON52430
- Lead Sponsor
- Merck
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
Participants are eligible to be included in the study only if all the following
criteria apply:
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
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 first-lineosimertinib.
-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 testing is not mandated prior to the start of study treatment
3. Woman: no woman of childbearing potential (WOCBP) or, use a highly effective
contraception. Man: contraception or no intercourse with a WOBCP.
Participants are excluded from the study if any of the following criteria apply:
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/gamma knife 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 National Cancer
Institute-Common Terminology Criteria for Adverse Events Version (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)
-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 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is objective response (confirmed complete response [CR] or<br /><br>partial response [PR]) determined according to Response Evaluation Criteria in<br /><br>Solid Tumors (RECIST) Version 1.1 as per Independent Review Committee (IRC). </p><br>
- Secondary Outcome Measures
Name Time Method