Brain metastases, Braf-V600 mutation-positive advanced solid tumor, Braf-V600 mutation-positive melanoma with central nervous system metastases Cancer
Conditions
Interventions
Current intervention as of 01/08/2022:
Participants will be allocated to receive either:
1. RO7276389 tablet orally (PO) alone once daily (QD) or twice daily (BID) or three times daily (TID) on every
Sponsors
Roche (United States)
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Have Eastern Cooperative Oncology Group (ECOG) Performance Status =2 2. Aged =18 years at the time of signing Informed consent form (ICF) 3. Life expectancy of >3 months 4. Documented BRAF-V600 mutation status of tumour tissue preferentially using an FDA-approved or CE-IVD genetic test 5. Confirmation of availability of archival tumour tissue for submission to the sponsor/central laboratory For Part 1 only: 1. Participants with histologically confirmed advanced/metastatic solid tumour or brain metastases with the measurable systemic disease per RECIST v1.1 (extracranial disease) or mRECIST-BM (intra-cranial disease) For Part 2 only: 1. Participants with histologically confirmed cutaneous melanoma with radiologically confirmed asymptomatic brain metastases per mRECIST-BM 2. Stable or improved CNS disease symptoms for at least 14 days before the start of study treatment
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 01/08/2022: 1. For Part 2 only: History of or current leptomeningeal metastases 2. Any metastasis requiring immediate local intervention 3. Uncontrolled tumour-related pain 4. Participants requiring narcotic pain medication must be on a stable regimen at the start of study treatment 5. Ascites, pleural effusion, or pericardial effusion requiring medical intervention (including use of diuretics) within 6 months prior to study entry 6. Active malignancy (other than the one under investigation) or a prior malignancy within the past two years prior to enrolment with some exceptions 7. Active uveitis, or any history of serous retinopathy or retinal vein occlusion 8. Current or history of Central Nervous System (CNS) disease unrelated to the malignancy under investigation, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease 9. Active autoimmune disease, or quiescent autoimmune disease with exacerbations/flares within 1 year prior to enrolment 10. Systemic anti-cancer therapy or small-molecular therapeutic(s), including but not limited to chemotherapy, investigational drugs, hormonal therapy and radiotherapy, and antibody-based agents all within 2 weeks or at least 5 half-lives, whichever is shorter, prior to start of study treatment 11. Treatment with stereotactic radiosurgery or craniotomy within 1 week prior to study treatment or treatment with whole brain radiotherapy within 3 months prior study treatment. Participants with local therapy should have a complete recovery with no neurological sequelae. 12. Radiation therapy to visceral metastases within 1 week prior to study treatment. Palliative radiotherapy is allowed. 13. Major surgical procedure other than for diagnosis within 2 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study 14. Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for =2 weeks prior to screening 15. Contraindication to cobimetinib or known hypersensitivity to any formulation component of cobimetinib (if applicable) 16. Participants with known hypersensitivity to BRAFi and/or MEK inhibitors (MEKi) 17. Increasing corticosteroid dose during the 14 days prior to initiation of study treatment or current dexamethasone or equivalent dose of >8 mg/day 18. Strong CYP3A inducers (including St. John's wort and hyperforin) are prohibited during study treatment and for 2 weeks after the last dose of cobimetinib or RO7276389 (whichever is later). 19. Concomitant treatment with anti-convulsants other than gabapentin, vigabatrin and levetiracetam are prohibited (e.g., carbamazepine, phenytoin, and phenobarbital due to strong CYP3A induction) during study treatment and for 2 weeks after the last dose of cobimetinib or RO7276389 (whichever is later) 20. For combination treatment with cobimetinib, moderate and strong CYP3A inducers and inhibitors are prohibited during study treatment and for 2 weeks after the last dose of cobimetinib or RO7276389 (whichever is later) 21. Concomitant treatment with drugs known to shorten the QT interval, e.g. rufinamide 22. Uncontrolled diabetes or symptomatic hyperglycemia 23. Any Grade =3 haemorrhage or bleeding event within 28 days of study treatment initiation 24. History of human immunodeficiency virus (HIV) positivity 25. Hepatitis B virus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Percentage of participants with Dose-Limiting Toxicities (DLTs) measured using the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0) between Day 1 Cycle 1 and Day 14 Cycle 1 (cycle length = 28 days) 2. Percentage of participants with adverse events measured using the NCI-CTCAE V5.0 between Day 1 Cycle 1 and Day 14 Cycle 1 (cycle length = 28 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Percentage of participants with adverse events measured using the NCI-CTCAE V5.0 between Day 1 Cycle 1 and up to 28 days after the last dose (approximately 24 months) 2. Number of participants with a clinically significant change from baseline in vital signs measured using vital signs recorded between baseline and up to 28 days after the last dose (approximately 24 months) 3. Number of participants with a clinically significant change from baseline in physical and neurological findings measured using physical and neurological examinations undertaken between baseline and up to 28 days after the last dose (approximately 24 months) 4. Number of participants with a clinically significant change from baseline in ECG readings measured using ECGs undertaken between baseline and up to 28 days after the last dose (approximately 24 months) 5. Number of participants with a clinically significant change from baseline in Left Ventricular Ejection Fraction (LVEF) safety parameter measured using descriptive statistics (individual listings) using echocardiogram, or Multiple-gated acquisition (MUGA) on Day 1 Cycle 2, Day 1 Cycle 5, and thereafter every 3 months on subsequent cycles (up to approximately 24 months) 6. Number of participants with a clinically significant change from baseline in laboratory test results measured using laboratory tests undertaken between baseline and up to 28 days after the last dose (approximately 24 months) 7. Objective Response Rate (ORR) measured using the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 (extracranial disease) at baseline, Day 1 Cycle 2, Day 1 Cycle 3, Day 1 Cycle 5, Day 1 Cycle 7, and thereafter every 8 weeks on subsequent cycles (up to approximately 24 months) 8. ORR as determined by the investigator using the Modified Response Assessment in Neuro-Oncology for Brain Metastases (mRECIST-BM; intra-cranial disease) criteria measured at baseline, Day 1 Cycle 2, Day 1 Cycle 3, Day 1 Cycle 5, Day 1 Cycle 7, and thereafter | — |
Countries
Belgium, Brazil, Denmark, New Zealand, Poland, Spain, Switzerland, United Kingdom
Contacts
Public ContactClinical Trials
Outcome results
None listed