MelanomaPhase 1NCT07121829
Tovorafenib (DAY101) or in Combination With Pimasertib for Participants With Melanoma and Other Solid Tumors
A Phase 1 study testing Tovorafenib and Tovorafenib Drug: Pimasertib in people with Melanoma and Solid Tumor, run by Day One Biopharmaceuticals, Inc. at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Melanoma, Solid Tumor, Pilocytic Astrocytoma
- What is being tested?
- Tovorafenib and Tovorafenib Drug: Pimasertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 2 May 2022to 18 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 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
Who cannot join
- 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
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 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
Canada2 sites
Princess Margaret Cancer Centre
Toronto, Ontario
The Hospital for Sick Children
Toronto, Ontario
About this study
Official title: A Phase 1b/2, Subprotocol of DAY101 in Combination With Pimasertib for Patients With Recurrent, Progressive, or Refractory Solid Tumors and MAPK Pathway Aberrations
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.
- Conditions
- Melanoma, Solid Tumor, Pilocytic Astrocytoma, Non Small Cell Lung Cancer, Colorectal Cancer, Pancreatic Cancer
- Being tested
- Tovorafenib, Tovorafenib Drug: Pimasertib
- Keywords
- DAY101, Mitogen-activated protein kinase, tovorafenib, pimasertib, DAY201
- Medical subject headings
- Melanoma, Astrocytoma, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TovorafenibDrug
Tovorafenib tablet for oral use.
Tovorafenib Drug: PimasertibDrug
Tovorafenib tablet for oral use. Pimasertib capsule for oral use
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Tovorafenib plus pimasertib Receives: Drug: Tovorafenib; Drug: Tovorafenib Drug: Pimasertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants who will report Treatment emergent adverse events (TEAEs) and serious TEAEs
Measured: Up to 30 days after the last dose of any study drug
Number of participants who will report clinically significant changes in vital signs
Measured: 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
Measured: Up to 30 days after the last dose of any study drug
Number of participants who will report clinically significant changes in hematology parameters
Measured: Up to 30 days after the last dose of any study drug
Number of participants with Dose limiting toxicities (DLTs)
Measured: Up to 30 days after the last dose of any study drug
Secondary outcomes (10)
Percentage of participants with complete overall response rate (ORR)
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
Measured: Up to 30 months
Duration of response (DOR)
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.
Measured: Up to 30 months
Progression Free Survival (PFS)
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.
Measured: Up to 30 months
Overall Survival (OS)
The interval from the date of the first dose until the recorded date of death due to any cause.
Measured: Up to 30 months
Time to Response
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.
Measured: Up to 30 months
Plasma concentration of DAY101
Measured: Cycles 1 through Cycle 11 (each cycle is 28 days)
Maximum drug concentration (Cmax) of DAY101
Measured: Cycle 1, Day 1 through Cycle 1, Day 22
Area Under the Curve from Time Zero to Last Measurable Concentration (AUC 0-last)
Measured: 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.
Measured: Up to 30 months
Change in expression levels of phosphorylated ERK (pERK) and Ki67 in pre and post treatment samples using immunohistochemistry methodology.
Measured: Up to 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2025
- Study start2 May 2022
- Primary completion18 Dec 2024
- Study completion18 Dec 2024
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 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
- NCT07121829
- Sponsor's protocol ID
- DAY101-102b
- Other IDs
- 2021-003768-29
- Status last verified
- Aug 2025
- First submitted
- 3 Jul 2025
- Last updated
- 14 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2, Subprotocol of DAY101 in Combination With Pimasertib for Patients With Recurrent, Progressive, or Refractory Solid Tumors and MAPK Pathway Aberrations
- ClinicalTrials.gov ID
- NCT07121829
- Acronym / sponsor ID
- DAY101-102b
- Conditions
- Melanoma, Solid Tumor, Pilocytic Astrocytoma, Non Small Cell Lung Cancer, Colorectal Cancer, Pancreatic Cancer
- Keywords
- DAY101, Mitogen-activated protein kinase, tovorafenib, pimasertib, DAY201
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Day One Biopharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 2 May 2022 (actual)
- Primary completion
- 18 Dec 2024 (actual)
- Study completion
- 18 Dec 2024 (actual)
- First posted
- 14 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: Tovorafenib, Drug: Tovorafenib Drug: PimasertibTovorafenib plus pimasertib |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TovorafenibTovorafenib tablet for oral use. | Drug | Experimental Arm |
| Tovorafenib Drug: PimasertibTovorafenib tablet for oral use. Pimasertib capsule for oral use | Drug | Experimental Arm |
Primary outcome
Number of participants who will report Treatment emergent adverse events (TEAEs) and serious TEAEs
Time frame: Up to 30 days after the last dose of any study drug
Number of participants who will report clinically significant changes in vital signs
Time frame: 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
Time frame: Up to 30 days after the last dose of any study drug
Number of participants who will report clinically significant changes in hematology parameters
Time frame: Up to 30 days after the last dose of any study drug
Number of participants with Dose limiting toxicities (DLTs)
Time frame: Up to 30 days after the last dose of any study drug
10 secondary outcomes
Percentage of participants with complete overall response rate (ORR)
Time frame: Up to 30 months
Duration of response (DOR)
Time frame: Up to 30 months
Progression Free Survival (PFS)
Time frame: Up to 30 months
Overall Survival (OS)
Time frame: Up to 30 months
Time to Response
Time frame: Up to 30 months
Plasma concentration of DAY101
Time frame: Cycles 1 through Cycle 11 (each cycle is 28 days)
Maximum drug concentration (Cmax) of DAY101
Time frame: Cycle 1, Day 1 through Cycle 1, Day 22
Area Under the Curve from Time Zero to Last Measurable Concentration (AUC 0-last)
Time frame: 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.
Time frame: Up to 30 months
Change in expression levels of phosphorylated ERK (pERK) and Ki67 in pre and post treatment samples using immunohistochemistry methodology.
Time frame: Up to 30 months
Results and safety
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tovorafenib and Tovorafenib Drug: Pimasertib in people with Melanoma and Solid Tumor, run by Day One Biopharmaceuticals, Inc. at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants who will report Treatment emergent adverse events (TEAEs) and serious TEAEs (time frame: Up to 30 days after the last dose of any study drug). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2025.