Brief Title: Tovorafenib (DAY101) Monotherapy or in Combination With Other Therapies for Patients With Melanoma and Other Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Phase 1b: Determine the safety of tovorafenib in combination with other therapies

Primary Outcome 1 - Timeframe: Up to 48 months

Primary Outcome 2 - Measure: Phase 1b: Determine the MTD and RP2D of tovorafenib in combination with other therapies

Primary Outcome 2 - Timeframe: Up to 48 months

Primary Outcome 3 - Measure: Phase 2: Evaluate the efficacy of tovorafenib monotherapy or in combination with other therapies

Primary Outcome 3 - Timeframe: Up to 48 months

CONDITION

• 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
• RAS Mutation
• RAF Mutation
• MEK Mutation

ELIGIBILITY

Inclusion Criteria:
* Signed informed consent by patients ≥ 18 years of age and, assent for patients ≥ 12 up to < 18 years of age - * Patients must have radiographically-recurrent or radiographically-progressive disease that is measurable using the appropriate tumor response criteria (e.g. RECIST version 1.1) - * 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
Substudy A-specific inclusion criterion:
* Patients must have a report of histologically confirmed diagnosis of melanoma or other solid tumor and a concurrent BRAF fusion, CRAF/RAF1 fusion, or CRAF/RAF1 amplification 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 agency.
Substudy B-specific inclusion criterion:
* Patients must have a report of histologically confirmed diagnosis of melanoma or other solid tumor and a concurrent MAPK pathway alteration (genomic alterations in RAS, RAF, MEK, or NF1) through a tumor or liquid biopsy as assessed by genomic sequencing, PCR, FISH, or another clinically accepted molecular diagnostic method recognized by local laboratory or agency.
Exclusion Criteria:
* Known presence of concurrent activating mutation

- * Patients with current evidence or a history of central serous retinopathy (CSR), retinal vein occlusion (RVO)
Substudy A-specific exclusion criterion:
* Prior therapy of any RAS- RAF-, MEK-, or ERK-directed inhibitor therapy

Gender: All

Minimum Age: 12 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 650-484-0899

Email: clinicaltrials@dayonebio.com

LOCATION