Clinical Trial Finder

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.

(Closed to Enrollment) 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) (Closed to Enrollment) Substudy A-specific exclusion criterion: - Prior therapy of any RAS- RAF-, MEK-, or ERK-directed inhibitor therapy

Study DAY101-102 (master study) and sub-studies will consist of a screening period, a treatment period, a safety follow-up period, and a long-term follow-up period where survival, status and subsequent anticancer therapies are collected. Tovorafenib will be evaluated alone or combined with a different targeted therapy in each sub-study. The Phase 1b part of each applicable sub-study will evaluate the safety of the combination and select the dose for the Phase 2 part. The Phase 2 part of each sub-study will evaluate anti-tumor activity. (Closed to Enrollment) Substudy A will enroll patients with recurrent or progressive melanoma or other solid tumors with BRAF fusion or CRAF/RAF1 fusions or amplification. Substudy B will enroll patients with recurrent or progressive melanoma or other solid tumors with alterations in the key proteins of the MAPK pathway.

Arms

Experimental: Arm #1 (Closed to Enrollment)

Tovorafenib monotherapy

Experimental: Arm #2

Tovorafenib plus pimasertib

Interventions

Drug: - Tovorafenib

Tovorafenib tablet for oral use.

Drug: - Pimasertib

Pimasertib capsule for oral use.