A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations

Inclusion Criteria

• •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.