A Phase IA/B Open-label Study to Evaluate Safety, Pharmacokinetics, and Preliminary Clinical Activity of RO7276389 alone and in Combination with Cobimetinib in Participants with BRAF-V600 Mutation-positive Advanced Solid Tumor or BRAF-V600 Mutation-positive Melanoma with Central Nervous System Metastases
Study Identifier:
WP43295
CT.gov Identifier:
N/A
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
Considering participating in a START clinical trial?
Study Summary
To find out the highest dose that a participant can tolerate and/or the recommended dose of RO7276389 by itself or in combination with cobimetinib.
To find out how safe RO7276389 by itself or in combination with cobimetinib at different doses will be and to find out what side-effects this treatment may cause
To find out if RO7276389 by itself or in combination with cobimetinib is effective against BRAF-mutated solid tumours or melanoma (a type of skin cancer).
To find out how RO7276389 by itself or in combination with cobimetinib will be distributed and eliminated from the body.
To find out the effect of food on the distribution and elimination of RO7276389 alone or in combination with cobimetinib from the body.
The objectives were to define the maximum tolerated dose (MTD), the recommended Phase 2 dose and additionally to characterize safety, PK/PD, and clinical outcomes.
To analyze ctDNA to explore BRAF V600 allele frequency (AF), monitor patient responses, and investigate resistance mechanisms at progression.
ctDNA was quantified by F1LCDx and/or F1Tracker. For longitudinal analysis, the change from baseline (CFB) at C1D15 and mutation profile at discontinuation were used. Baseline tumor tissue was analyzed by F1CDx.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I
Sex
Female & Male
Age
18+ years
Study Drug
Read More
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Have Eastern Cooperative Oncology Group (ECOG) Performance Status < or = 2
- Aged >or=18 years at the time of signing Informed consent form (ICF)
- Life expectancy of >3 months
- Documented BRAF-V600 mutation status of tumour tissue preferentially using an FDA-approved or CE-IVD genetic test
- Confirmation of availability of archival tumour tissue for submission to the sponsor/central laboratory
- For Part 1 only:
- 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:
- Participants with histologically confirmed cutaneous melanoma with radiologically confirmed asymptomatic brain metastases per mRECIST-BM
- Stable or improved CNS disease symptoms for at least 14 days before the start of study treatment
Exclusion criteria
- History of or current leptomeningeal metastases
- Any metastasis requiring immediate local intervention
- Uncontrolled tumour-related pain
- Participants requiring narcotic pain medication must be on a stable regimen at the start of study treatment
- Ascites, pleural effusion, or pericardial effusion requiring medical intervention (including use of diuretics) within 6 months prior to study entry
- Active malignancy (other than the one under investigation) or a prior malignancy within the past two years prior to enrolment with some exceptions
- Active uveitis, or any history of serous retinopathy or retinal vein occlusion
- Current or history of Central Nervous System (CNS) disease unrelated to the malignancy under investigation, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- Active autoimmune disease, or quiescent autoimmune disease with exacerbations/flares within 1 year prior to enrolment
- 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
- 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.
- Radiation therapy to visceral metastases within 1 week prior to study treatment. Palliative radiotherapy is allowed.
- 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
- 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 >or=2 weeks prior to screening
- Contraindication to cobimetinib or known hypersensitivity to any formulation component of cobimetinib (if applicable)
- Participants with known hypersensitivity to BRAFi and/or MEK inhibitors (MEKi)
- Increasing corticosteroid dose during the 14 days prior to initiation of study treatment or current dexamethasone or equivalent dose of >8 mg/day
- Concomitant treatment with CYP3A-inducing anti-epileptic drugs (such as 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)
- St. John's wort and hyperforin being strong CYP3A inducers are prohibited during study treatment and for 2 weeks after the last dose of cobimetinib or RO7276389 (whichever is later)
- Concomitant treatment with drugs known to shorten the QT interval, e.g. rufinamide
- Uncontrolled diabetes or symptomatic hyperglycaemia
- Any Grade >or=3 haemorrhage or bleeding event within 28 days of study treatment initiation
- History of human immunodeficiency virus (HIV) positivity
- Hepatitis B virus (HBV) infection (chronic or acute)
- Hepatitis C virus (HCV) infection (chronic or acute)
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.
Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Irene Moreno
Status
Recruitment Complete
Condition(s) Treated at Site
Bowel (Colorectal)
Melanoma
Solid Tumor
Metastatic Cancer