Tovorafenib (DAY101) or in Combination With Pimasertib for Participants With Melanoma and Other Solid Tumors

NCT07121829 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: DAY101-102b2021-003768-29
• Study Type: interventional
• Target: 44
• Locations: 2 countries
• Sites: 10

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.

Conditions

Melanoma; Solid Tumor; Pilocytic Astrocytoma; Non Small Cell Lung Cancer; Colorectal Cancer; Pancreatic Cancer; MAP Kinase Family Gene Mutation; RAS Mutation; RAF Mutation; MEK Mutation

Keywords

DAY101; Mitogen-activated protein kinase; tovorafenib; pimasertib; DAY201

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (10)

• Percentage of participants with complete overall response rate (ORR)

  Up to 30 months

• Duration of response (DOR)

  Up to 30 months

• Progression Free Survival (PFS)

  Up to 30 months

• Overall Survival (OS)

  Up to 30 months

• Time to Response

  Up to 30 months

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Tovorafenib plus pimasertib

Drug: Tovorafenib; Drug: Tovorafenib Drug: Pimasertib

Interventions

Tovorafenib DRUG

Tovorafenib tablet for oral use.

Experimental Arm

Tovorafenib Drug: Pimasertib DRUG

Tovorafenib tablet for oral use. Pimasertib capsule for oral use

Experimental Arm

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Day One Biopharmaceuticals, Inc.: lead

Study Sites (10)

The Angeles Clinic

Los Angeles, California, 90025, United States

Location

Hoag Health

Newport Beach, California, 92663, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

Community North Cancer Center

Indianapolis, Indiana, 46250, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

Location

vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Melanoma; Astrocytoma; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Pancreatic Neoplasms

Interventions

tovorafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2025
• First Posted: August 14, 2025
• Study Start: May 2, 2022
• Primary Completion: December 18, 2024
• Study Completion: December 18, 2024
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (8); CA (2)