MelanomaPhase 2NCT04985604
Tovorafenib (DAY101) Monotherapy for Patients With Melanoma and Other Solid Tumors
A Phase 2 study testing Tovorafenib in people with Melanoma and Solid Tumor, run by Day One Biopharmaceuticals, Inc. at 20 sites in 7 countries.
Trial summary
This is a Phase 2, multi-center, open-label to evaluate the efficacy and safety of tovorafenib (DAY101) in participants ≥12 years of age with recurrent or progressive melanoma or solid tumors with BRAF fusion or CRAF/RAF1 fusions or amplification. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Melanoma, Solid Tumor, CRAF Gene Amplification
- What is being tested?
- Tovorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 20 sitesin 7 countries
- Study dates
- 15 Jul 2021to 8 Jul 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Signed informed consent by participants ≥ 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 histologically confirmed diagnosis of melanoma or other solid tumor and a BRAF fusion, CRAF/RAF1 fusion, or CRAF/RAF1 amplifications 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-recurrent or radiographically-progressive disease that is measurable using the appropriate tumor response criteria (e.g. RECIST version 1.1 or RANO).
- Archival tumor tissue (preferably less than 3 years old) or fresh tumor tissue for correlative studies is required
- If brain metastases are present, they must have been previously treated and be stable as assessed by radiographic imaging
Who cannot join
- Prior therapy of any RAS-, RAF-, MEK-, or ERK-directed inhibitor therapy
- Known presence of concurrent activating mutation
- Participants with current evidence or a history of central serous retinopathy (CSR), retinal vein occlusion (RVO)
Trial locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
United States8 sites
University of Colorado Hospital
Aurora, Colorado, 80045
Community North Cancer Center
Indianapolis, Indiana, 46250
Cancer Specialists of North Florida
Jacksonville, Florida, 32256
The Angeles Clinic
Los Angeles, California, 90025
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Hoag Health
Newport Beach, California, 92663
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15213
OHSU Knight Cancer Institute
Portland, Oregon, 97239
South Korea4 sites
Dong-A University Hospital
Busan
Asan Medical Center
Seoul
Samsung Medical Center
Seoul
Severance Hospital, Yonsei University Health System
Seoul
Spain3 sites
Hospital Clinic Barcelona
Barcelona
Hospital Universitari Vall d'Hebron
Barcelona
Hospital Universitario Ramón y Cajal
Madrid
Canada2 sites
Princess Margaret Cancer Centre
Toronto, Ontario
The Hospital for Sick Children
Toronto, Ontario
About this study
Official title: A Phase 2, Subprotocol of DAY101 Monotherapy for Patients With Recurrent, Progressive, or Refractory Solid Tumors With MAPK Pathway Aberrations
This is a Phase 2, multi-center, open-label to evaluate the efficacy and safety of tovorafenib (DAY101) in participants ≥12 years of age with recurrent or progressive melanoma or solid tumors with BRAF fusion or CRAF/RAF1 fusions or amplification.
- Conditions
- Melanoma, Solid Tumor, CRAF Gene Amplification, RAF1 Gene Amplification, BRAF Gene Fusion, BRAF Fusion
- Being tested
- Tovorafenib
- Keywords
- BRAF fusion, CRAF/RAF1 fusion, CRAF/RAF1 amplification
- Medical subject headings
- Melanoma, Thyroid Cancer, Papillary, Astrocytoma, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Pancreatic Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TovorafenibDrug
Also called DAY101
Tovorafenib tablet for oral use.
| Study group | Role | What they receive |
|---|---|---|
| Melanoma Cohort | Experimental | Tovorafenib monotherapy Receives: Drug: Tovorafenib |
| Tissue Agnostic Cohort | Experimental | Tovorafenib monotherapy Receives: Drug: Tovorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) by the Investigator
ORR was defined as the percentage of participants with the best overall confirmed response of complete response (CR) or partial response (PR) according to the appropriate response assessment criteria including Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for the disease setting as assessed by the Investigator. CR or PR was confirmed at a subsequent scan (>=4 weeks) if the criteria for each are met . The exact 95% confidence intervals (CIs) were calculated using Clopper-Pearson method.
Measured: Up to 23 months
Secondary outcomes (7)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. An AE is considered to be treatment-emergent if it has a start date/time on or after the first administration of study drug until 30 days after the last dose of study drug and before the start of subsequent therapy, whichever comes earlier. The distribution of AEs was analyzed by the type, frequency and severity for TEAEs.
Measured: Up to 23 months
Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline
Blood samples were collected for the analysis of following hematology parameters: anemia, neutrophil count decreased and white blood cell decreased. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G2, G3, and G4 are presented. The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Measured: Baseline and up to 23 months
Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline
Blood samples were collected for the analysis of following chemistry parameters: creatine phosphokinase (CPK) increased, hypokalemia, hypoalbuminemia, hypercalcemia, hypocalcemia and hyponatremia. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G2, G3, and G4 are presented. The laboratory parameters were graded according to CTCAE version 5.
Measured: Baseline and up to 23 months
Duration of Response (DOR) in Participants With Best Overall Response
Duration of response was defined as 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 RECIST 1.1 or RANO criteria or death due to any cause, whichever occurs earlier. DOR was estimated using Kaplan-Meier method.
Measured: Up to 23 months
Duration of Progression Free Survival
Progression free survival was defined as the interval from the date of the first dose to the first occurrence of radiographic disease progression based on RECIST 1.1 or RANO criteria or death due to any cause, whichever occurs earlier. Progression free survival was estimated using Kaplan-Meier method.
Measured: Up to 23 months
Duration of Overall Survival
Overall survival is defined as the interval from the date of the first dose until the recorded date of death due to any cause. Overall survival was estimated using Kaplan-Meier method.
Measured: Up to 23 months
Time to Response
Time to Response was defined in participants with best overall response of complete response or partial response as determined by Investigator. It is the interval from the date of the first dose to date of first documentation of tumor response that was subsequently confirmed by investigator assessment.
Measured: Up to 23 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2021
- Study start15 Jul 2021
- Primary completion8 Jul 2024
- Study completion8 Jul 2024
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Day One Biopharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04985604
- Sponsor's protocol ID
- DAY101-102a
- Other IDs
- 2021-003768-29
- Status last verified
- Sep 2025
- First submitted
- 23 Jun 2021
- Last updated
- 2 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Vieito M, Cabanas EG, Mehmi I, Gaudy-Marqueste C, O'Neil BH, Medina TM, Body AL, Arance A, Kummar S, Najjar YG, Bedard PL, Rankin A, Chu C, McKenna C, Hume S, Kopp LM, Lee J. Type II RAF Inhibitor Tovorafenib in Recurrent/Refractory Melanoma or Other Solid Tumors With BRAF Fusions or CRAF/RAF1 Fusions or Amplification: Phase II FIRELIGHT-1 Substudy. JCO Precis Oncol. 2026 Oct;10(10):e2501187. doi: 10.1200/PO-25-01187. Epub 2026 Oct 2.
PubMed 42826365