A FIH Study of PF-07284890 in Participants With BRAF V600 Mutant Solid Tumors With and Without Brain Involvement

A TWO-PART, PHASE 1A/B, OPEN-LABEL, MULTICENTER TRIAL EVALUATING PHARMACOKINETICS, SAFETY AND EFFICACY OF PF 07284890 (ARRY 461) IN PARTICIPANTS WITH BRAF V600 MUTANT SOLID TUMORS WITH AND WITHOUT BRAIN INVOLVEMENT

First-in-human study to assess safety, tolerability, PK, and preliminary activity of PF-07284890 as a single agent and in combination with binimetinib in participants with BRAF V600-mutated advanced solid tumor malignancies with and without brain involvement.

Inclusion Criteria:

• Age ≥16 years at the time of consent

• Histologically confirmed diagnosis of advanced/metastatic solid tumor including primary brain tumor

• Documented evidence of a BRAF V600 mutation in tumor tissue or blood

• Confirmation of availability of adequate tumor tissue for submission to the sponsor/central laboratory

• Presence or absence of brain involvement unless specified below

• Dose Expansion (Part B)

  • Cohort 1, 2, 3, 4: melanoma with at least 1 parenchymal brain lesion
  • Cohort 1,3: asymptomatic in the brain for at least 14 days prior to start of study treatment
  • Cohort 2,4: symptomatic in the brain within 14 days prior to the start of study treatment
  • Cohort 5: any solid tumor that does not meet requirements for Cohorts 1-4, history of or current leptomeningeal metastases.
  • Optional Cohort 6 (DDI Sub-study) and 7 (Food-Effect): if brain involvement present, must be asymptomatic

• Disease progression despite prior treatment and no acceptable alternative treatment options available unless specified below

• Dose Expansion (Part B)

  • Cohort 1, 2: No prior BRAF inhibitor in the metastatic setting or in the adjuvant setting within 6 months of study treatment
  • Cohort 3, 4: Required prior BRAF inhibitor in the metastatic setting or in the adjuvant setting within 6 months of treatment

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Exclusion Criteria:

• Brain metastasis/primary brain tumor requiring immediate local intervention
• History of or current leptomeningeal metastases
• Any other active malignancy within 2 years prior to enrollment
• Radiation therapy to visceral metastases within 14 days prior to study treatment. WBRT within 28 days prior to study treatment.
• Systemic anti-cancer therapy or small-molecular therapeutic(s) within 2 weeks prior to start of study treatment; Antibody based agents within 4 weeks prior to start of study treatment.
• History or current evidence of RVO or current risk factors for RVO; History of retinal degenerative disease