F8394-201: This study is recruiting people with locally advanced or metastatic solid cancers that have BRAF alterations to evaluate a targeted drug called PlixorafenibA Phase 2 Master Protocol to Assess the Efficacy and Safety of FORE8394, an Inhibitor of BRAF Class 1 and Class 2 Alterations, in Participants With Cancer Harboring BRAF Alterations

Inclusion

Subprotocol A:

1. Male and female, ≥10 years of age, and weighing ≥30 kg.
2. Histologic diagnosis of a solid tumor or primary CNS tumor.
3. Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically validated test by DNA sequencing or RNA (transcriptome) sequencing.
4. Have an archival tissue sample available meeting protocol requirements.
5. Consent to provide scan(s) prior to baseline to assess change in tumor trajectory.
6. Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.
7. All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline.

Subprotocol B:

1. Male and female, ≥10 years of age, and weighing ≥30 kg.

2. Histological diagnosis of a primary CNS tumor, including but not limited to the following:

   1. Adults (≥18 years) with Grade 1-4 glioma or glioneuronal tumor (including glioblastoma, anaplastic astrocytoma, high grade astrocytoma with piloid features, pilocytic astrocytoma, gliosarcoma, anaplastic pleomorphic xanthoastrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, not otherwise specified [NOS], ganglioglioma, or recurrent LGG). OR
   2. Pediatric patients (10-17 years of age) with a Grade 3 or 4 glioma or glioneuronal tumor, including those with a prior, histologically confirmed, diagnosis of a low-grade glioma or glioneuronal tumor and now have radiographic or histopathological findings consistent with WHO [2021] Grade 3 or 4 primary CNS tumor.
   3. Participants must have unresectable, locally advanced or metastatic disease that:

   i. Had prior treatment with radiotherapy and/or first-line chemotherapy or concurrent chemoradiation therapy OR

   • Note: Participants who have a WHO Grade 3 or 4 glioma for whom chemotherapy and/or radiotherapy is not considered standard of care may remain eligible for the study.

   ii. Is intolerant to available therapies OR iii. The investigator has determined that treatment with standard therapy is not appropriate.

3. Documented BRAF V600E mutation in tumor and/or liquid biopsy detected by an analytically validated test at CLIA or CLIA-equivalent laboratory approved by sponsor or sponsor-designated central test.
4. An archival tissue sample available meeting protocol requirements, or fresh biopsy is required if the archival sample is not available for retrospective confirmation test.
5. Consent to provide scan(s) prior to baseline to assess change in tumor trajectory.
6. Measurable disease based upon specified response criteria, as determined by the radiographic BICR.
7. All adverse events related to prior therapies (eg, chemotherapy, radiotherapy, surgery) must have resolved to Grade 1 or baseline.
8. Participants who are receiving corticosteroid treatment must be on a stable or decreasing dose of ≤8 mg/day of dexamethasone or equivalent corticosteroid treatment for 7 days prior to first dose of study treatments.

Subprotocol C:

1. Male and female, ≥10 years of age, and weighing ≥30 kg.
2. Histologic diagnosis of a rare BRAF V600E-mutated solid tumor that is unresectable, locally advanced or metastatic.
3. Measurable disease on CT, MRI, or physical exam
4. Documented BRAF V600E mutation in tumor and/or liquid biopsy detected by an analytically validated test.
5. Have an archival tissue sample available meeting protocol requirements.
6. Consent to provide scan(s) prior to baseline to assess change in tumor trajectory
7. Received all available standard therapy, is intolerant to available therapies, or the investigator has determined that treatment with standard therapy is not appropriate.

Subprotocol D:

1. Male and female, 18 - 65 years of age.
2. Histologic diagnosis of a solid tumor harboring a BRAF V600E mutation and not eligible for other subprotocols.
3. Measurable disease on CT, MRI, or physical exam.
4. Evidence of BRAF V600E mutation in tumor and/or blood detected by genomic tests.
5. Consent to provide a tumor biopsy.
6. Willingness to comply with the ECG substudy procedures.
7. All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline.