Tovorafenib (DAY101) Monotherapy for Patients With Melanoma and Other Solid Tumors

NCT04985604 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: DAY101-102a2021-003768-29
• Study Type: interventional
• Target: 23
• Locations: 7 countries
• Sites: 20

Brief 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.

Conditions

Melanoma; Solid Tumor; CRAF Gene Amplification; RAF1 Gene Amplification; BRAF Gene Fusion; BRAF Fusion; CRAF Gene Fusion; CRAF Fusion; RAF1 Gene Fusion; RAF1 Fusion; Thyroid Cancer, Papillary; Spitzoid Melanoma; Pilocytic Astrocytoma; Pilocytic Astrocytoma, Adult; Non Small Cell Lung Cancer; Non-Small Cell Adenocarcinoma; Colorectal Cancer; Pancreatic Acinar Carcinoma; Spitzoid Malignant Melanoma; Bladder Cancer; Bladder Urothelial Carcinoma; MAP Kinase Family Gene Mutation; RAF Mutation

Keywords

BRAF fusion; CRAF/RAF1 fusion; CRAF/RAF1 amplification

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 23 months

Secondary Outcomes (7)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  Up to 23 months

• Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-baseline Relative to Baseline

  Baseline and up to 23 months

• Number of Participants With Worst Case Chemistry Results by Maximum Grade Increase Post-baseline Relative to Baseline

  Baseline and up to 23 months

• Duration of Response (DOR) in Participants With Best Overall Response

  Up to 23 months

• Duration of Progression Free Survival

  Up to 23 months

Study Arms (2)

Melanoma Cohort

EXPERIMENTAL

Tovorafenib monotherapy

Drug: Tovorafenib

Tissue Agnostic Cohort

EXPERIMENTAL

Tovorafenib monotherapy

Drug: Tovorafenib

Interventions

Tovorafenib DRUG

Tovorafenib tablet for oral use.

Also known as: DAY101

Melanoma Cohort; Tissue Agnostic Cohort

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 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Day One Biopharmaceuticals, Inc.: lead

Study Sites (20)

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

Monash Medical Centre

Clayton, Victoria, Australia

Location

Antwerp University Hospital

Edegem, Belgium

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, Canada

Location

Hopital de La Timone - APHM

Marseille, Bouches-du-Rhône, France

Location

Dong-A University Hospital

Busan, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Hospital Clinic Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

MeSH Terms

Conditions

Melanoma; Thyroid Cancer, Papillary; Astrocytoma; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Pancreatic Neoplasms; Urinary Bladder 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; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Thyroid Neoplasms; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Glioma; Neoplasms, Neuroepithelial; 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; Pancreatic Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Study Director
• Organization: Day One Biopharmaceuticals, Inc.

clinicaltrials@dayonebio.com

1-650-484-0899

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: August 2, 2021
• Study Start: July 15, 2021
• Primary Completion: July 8, 2024
• Study Completion: July 8, 2024
• Last Updated: October 2, 2025
• Results First Posted: October 2, 2025

Record last verified: 2025-09

Locations

AU (1); KR (4); FR (1); ES (3); BE (1); CA (2); US (8)