A study to evaluate the safety, tolerability, processing by the body and effectiveness against BRAF-mutated solid tumours or melanoma of RO7276389 by itself or in combination with cobimetinib
- Conditions
- Brain metastases, Braf-V600 mutation-positive advanced solid tumor, Braf-V600 mutation-positive melanoma with central nervous system metastasesCancer
- Registration Number
- ISRCTN13713551
- Lead Sponsor
- Roche (United States)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 292
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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)<br>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 Outcome Measures
Name Time Method