None listed
Conditions
Brief summary
This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program, which is registered on ANZCTR with ID ACTRN12616000908437. This substudy will evaluate the activity of tepotinib in a population of participants with metastatic non-small cell lung cancers (NSCLC) harbouring METex14 skipping mutations identified using comprehensive genomic profiling (CGP). Who is it for? You may be eligible to join the study if you are aged 18 years and older, with pathologically confirmed metastatic NSCLC. Your tumour will need to harbour METex14 skipping mutations identified using CGP. Study details: Participants will receive tepotinib treatment. The tepotinib is to be taken orally, at 500mg once daily (days 1 to 21 in a 21-day treatment cycle). Tepotinib will be given to participants continuously as long as they and their doctor agree there is a benefit from treatment. Participants will undergo imaging assessments at 6 weekly intervals from first treatment until 18 weeks, and then 12 weekly intervals until progression. Safety and tolerability of treatment will be assessed at 3 weekly intervals. Health related quality of life during treatment will be assessed at 3 weekly intervals and then every 9 weeks after end of treatment for 12 months, and then every 12 weeks until progression. We cannot guarantee that participants will receive any benefits from this study. This study is being carried out to improve the way we treat cancer patients who may have limited treatment options available to them. It is hoped that tepotinib will be well tolerated and will improve outcomes for future patients, however, there may be no clear benefit from participation in this study.
Interventions
Participants will receive continuous tepotinib. Tepotinib will be administered as tablets, to be taken orally by participants, at a dose of 500mg daily (days 1 to 21 in a 21-day treatment cycle). Tepotinib is to be taken continuously with no interruption between cycles.
If participants experience any severe (grade 3-4) adverse events, treatment will be withheld until the adverse event is resolved (grade 0-1). If participants experience intolerable toxicity, tepotinib dose may be reduced to 250m
Participants will receive continuous tepotinib. Tepotinib will be administered as tablets, to be taken orally by participants, at a dose of 500mg daily (days 1 to 21 in a 21-day treatment cycle). Tepotinib is to be taken continuously with no interruption between cycles. If participants experience any severe (grade 3-4) adverse events, treatment will be withheld until the adverse event is resolved (grade 0-1). If participants experience intolerable toxicity, tepotinib dose may be reduced to 250mg once daily. If a second dose reduction is required, the patient should discontinue study treatment. Participants will receive tepotinib until disease progression is documented, intolerable toxicity or withdrawal for another reason. Participants will be asked to return unused drug and empty drug containers at each return visit. The Pharmacy Department at participating institutions will maintain a record of drugs dispensed for each participant.
Sponsors
The University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults, aged 18 years and older, with newly diagnosed metastatic non-squamous NSCLC; 2. METex14 skipping mutation identified using CGP; 3. Confirmation of molecular eligibility by the molecular tumour board; 4. Measurable disease as assessed by RECIST 1.1; In the event of evaluable but non-measurable disease, eligibility must be confirmed by the ASPiRATION study chair or delegate through contacting the NHMRC CTC; 5. ECOG 0 to 2; 6. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug): a. bone marrow function; platelets greater than or equal to 100 x 10^9/L, ANC greater than or equal to 1.5 x 10^9/L, and haemoglobin greater than or equal to 90g/L (5.6mmol/L); b. liver function; ALT/AST less than or equal to 3xULN (in the absence of liver metastases, less than or equal to 5xULN for patients with liver involvement) and total bilirubin less than or equal to 1.5xULN; c. renal function; serum creatinine less than or equal to 1.5xULN; 7. Life expectancy greater than or equal to 12 weeks; 8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments; 9. Signed, written informed consent to participation in the specific treatment substudy.
Exclusion criteria
1. Prior systemic therapy for advanced disease. Up to two cycles of systemic therapy (excluding prior MET inhibitor treatment) while awaiting the results of CGP testing are permitted. 2. Prior MET/HGF pathway inhibitor treatment; 3. Known history of hypersensitivity or contraindication to tepotinib; 4. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with tepotinib, including: a. Known history of interstitial lung disease or drug-induced pneumonitis requiring steroid treatment b. Congenital QT syndrome or baseline QTc >500ms 5. Active CNS involvement. Patients with stable neurological function, on stable anticonvulsants and/or steroids less than or equal to 10 mg prednisone equivalent over 4 weeks are eligible; 6. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol; 7. Treatment with any of the following anti-cancer therapies prior to the first dose of tepotinib: a. Radiation therapy, major surgery, or tumour embolization within 14 days prior to the first dose of study treatment. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions; b. Any systemic therapy within 28 days prior to the first dose of tepotinib; 8. Administration of any investigational treatment within 28 days prior to receiving the first dose of tepotinib; 9. Prior or concurrent malignancy. History of another primary malignancy except for: a. Malignancy treated with curative intent and with no known active disease within 2 years before consent to molecular screening and of low potential risk for recurrence; b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; c. Adequately treated carcinoma-in-situ without evidence of disease; 10. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.
Outcome results
None listed