Tovorafenib (DAY101) or in Combination With Pimasertib for Participants With Melanoma and Other Solid Tumors
- Conditions
- MelanomaPancreatic CancerMAP Kinase Family Gene MutationRAS MutationSolid TumorRAF MutationPilocytic AstrocytomaColorectal CancerNon Small Cell Lung CancerMEK Mutation
- Interventions
- Registration Number
- NCT07121829
- Lead Sponsor
- Day One Biopharmaceuticals, Inc.
- Brief Summary
This is a subprotocol of Master Protocol DAY101-102 and is a Phase 1b/2, multi-center, open label subprotocol of participants ≥12 years of age, with recurrent or progressive solid tumors with alterations in the key proteins of the MAPK pathway, such as tumors that harbor RAS or RAF alterations.
\*Note: Study concluded as Phase 1b only.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 44
- Signed informed consent by participant ≥12 years of age; either a Consent or an Assent Form will be provided to the patient based on their capacity, local regulations, and guidelines.
- Participants must have a report of histologically confirmed diagnosis of tumor and a concurrent MAPK pathway alteration (genomic alterations in RAS, RAF, MEK, or NF1) obtained through a tumor or liquid biopsy as assessed by genomic sequencing, polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or another clinically accepted molecular diagnostic method recognized by local laboratory or regulatory agency
- Participants must have radiographically stable, recurrent or progressive disease that is measurable using the appropriate tumor response criteria eg, (RECIST version 1.1, RANO)
- Archival tumor tissue should be preferably less than 3 years old. If unavailable, a freshly acquired tumor tissue biopsy or liquid biopsy is required
- If brain metastases are present, they must have been previously treated and be stable as assessed by radiographic imaging
- Known presence of concurrent activating alterations
- Participants with current evidence or a history of serous retinopathy (SR), retinal vein occlusion (RVO) or ophthalmopathy present at screening or baseline who would be considered at risk for SR or RVO
- Participants who have an unstable neurological condition, despite adequate treatment (eg, uncontrolled seizures)
- Participants with history of acute neurological events (such as intracranial or subarachnoid hemorrhage, stroke, intracranial trauma) within the past 6 months
- History of second malignancy within 3 years prior to study treatment except for curatively treated cervical cancer in situ, non-melanoma skin cancer, or superficial bladder cancer
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental Arm Tovorafenib Tovorafenib plus pimasertib
- Primary Outcome Measures
Name Time Method Number of participants who will report Treatment emergent adverse events (TEAEs) and serious TEAEs Up to 30 days after the last dose of any study drug Number of participants who will report clinically significant changes in vital signs Up to 30 days after the last dose of any study drug Number of participants who will report clinically significant changes in clinical chemistry parameters Up to 30 days after the last dose of any study drug Number of participants who will report clinically significant changes in hematology parameters Up to 30 days after the last dose of any study drug Number of participants with Dose limiting toxicities (DLTs) Up to 30 days after the last dose of any study drug
- Secondary Outcome Measures
Name Time Method Percentage of participants with complete overall response rate (ORR) Up to 30 months ORR as assessed by the proportion of participants with the best overall confirmed response of complete response (CR) or partial response (PR) according to the appropriate tumor response criteria as assessed by Investigator
Duration of response (DOR) Up to 30 months The interval from the date of the first documentation of tumor response (CR or PR) that was subsequently confirmed by investigator assessment to the date of first occurrence of radiographic disease progression based on appropriate tumor response criteria as assessed by investigator or death due to any cause, whichever occurs earlier.
Progression Free Survival (PFS) Up to 30 months The interval from the date of the first dose to the first occurrence of radiographic disease progression based on appropriate tumor response criteria as assessed by investigator or death due to any cause, whichever occurs earlier.
Overall Survival (OS) Up to 30 months The interval from the date of the first dose until the recorded date of death due to any cause.
Time to Response Up to 30 months Defined in participants with best overall response of CR or PR as determined by Investigator, time to response is defined as the interval from the date of the first dose to date of first documentation of tumor response (CR or PR) that was subsequently confirmed by investigator assessment.
Plasma concentration of DAY101 Cycles 1 through Cycle 11 (each cycle is 28 days) Maximum drug concentration (Cmax) of DAY101 Cycle 1, Day 1 through Cycle 1, Day 22 Area Under the Curve from Time Zero to Last Measurable Concentration (AUC 0-last) Cycle 1, Day 1 through Cycle 1, Day 22 Change in gene expression levels in pre and post treatment samples using RNA sequencing (RNA seq) analysis. Up to 30 months Change in expression levels of phosphorylated ERK (pERK) and Ki67 in pre and post treatment samples using immunohistochemistry methodology. Up to 30 months
Trial Locations
- Locations (10)
The Angeles Clinic
🇺🇸Los Angeles, California, United States
Hoag Health
🇺🇸Newport Beach, California, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Community North Cancer Center
🇺🇸Indianapolis, Indiana, United States
OHSU Knight Cancer Institute
🇺🇸Portland, Oregon, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
The Angeles Clinic🇺🇸Los Angeles, California, United States