CNS

A 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

Brief Summary: The objective of this Master Protocol is to evaluate the efficacy and safety of plixorafenib in participants with locally advanced or metastatic solid tumors, or recurrent or progressive primary central nervous system (CNS) tumors harboring BRAF fusions, or in participants with rare BRAF V600-mutated solid tumors, melanoma, thyroid, or recurrent primary CNS tumors.

Key Eligibility Criteria:

• Subprotocol A:
  • Histologic diagnosis of a solid tumor or primary CNS tumor.
  • Documentation of BRAF gene fusion in tumor and/or blood detected by an analytically validated test by DNA sequencing or RNA (transcriptome) sequencing.
• Subprotocol B:
  • Histological diagnosis of a primary CNS tumor, including but not limited to the following:
    • Adults (≥18 years) with Grade 1-4 glioma or glioneuronal tumor OR
    • Pediatric patients (10-17 years of age) with a Grade 3 or 4 glioma or glioneuronal tumor
  • Documented BRAF V600E mutation in tumor 
• Subprotocol C:
  • Histologic diagnosis of a rare BRAF V600E-mutated solid tumor that is unresectable, locally advanced or metastatic
• Subprotocol D:
  • Histologic diagnosis of a solid tumor harboring a BRAF V600E mutation and not eligible for other subprotocols.
• Prior treatment with RAF/BRAF inhibitors active for Class 2 BRAF alterations for advanced unresectable or metastatic disease excluded.
• Prior treatment with a MEK inhibitor excluded.

A phase 3 open-label, randomized, controlled study to evaluate the efficacy and safety of petosemtamab compared with investigator's choice monotherapy treatment in previously treated patients with incurable, metastatic/recurrent head and neck squamous cell carcinoma (MCLA-158-CL02)

MOA: Petosemtamab is a bispecific antibody targeting EGFR and LGR5

Key Eligibility Criteria:

• Metastatic or locally advanced HNSCC not amenable to standard therapy with curative intent
• Progressed on or after:
  • Anti-PD-1 therapy AND
  • Plt-containing therapy for R/M disease or if disease progressed within 6 months of plt-based therapy for locally advanced disease
    • Pts should not have received >1 line of chemotherapy in incurable R/M setting
• Eligible primary tumor locations: OP, OC, HP, LX
• OPC only: p16 status by local lab IHC or central testing
• No prior anti-EGFRs unless cetuximab + radiotherapy multimodal treatment of local disease and PD ≥ 1 year post cetuximab
• Baseline fresh/archival FFPE tumor sample from R/M primary site
• Measurable disease per RECIST v1.1