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

Pfizer

Status and phase: Terminated; Phase 1

Conditions: Malignant Melanoma; Brain Neoplasms, Primary; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Malignant Neoplasms

Treatments: Drug: Midazolam; Drug: PF-07284890; Drug: Binimetinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04543188

2022-003184-23 (EudraCT Number)

C4471001

Details and patient eligibility

About

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.

Enrollment: 65 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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65 participants in 9 patient groups

PF-07284890 (Part A monotherapy)

Experimental group

Description:

Monotherapy dose escalation of PF-07284890

Treatment:

Drug: PF-07284890

PF-07284890+binimetinib (Part A combo-therapy)

Experimental group

Description:

Combination dose escalation of PF-07284890 + binimetinib

Treatment:

Drug: Binimetinib

Drug: PF-07284890

Expansion Phase (Part B, Cohort 1)

Experimental group

Description:

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with asymptomatic brain involvement, and no prior BRAF or MEK inhibitor utilization

Treatment:

Drug: Binimetinib

Drug: PF-07284890

Expansion Phase (Part B, Cohort 2)

Experimental group

Description:

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with symptomatic brain involvement, and no prior BRAF or MEK inhibitor utilization

Treatment:

Drug: Binimetinib

Drug: PF-07284890

Expansion Phase (Part B, Cohort 3)

Experimental group

Description:

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with asymptomatic brain involvement, and prior BRAF inhibitor utilization

Treatment:

Drug: Binimetinib

Drug: PF-07284890

Expansion Phase (Part B, Cohort 4)

Experimental group

Description:

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 melanoma, with symptomatic brain involvement, and prior BRAF inhibitor utilization

Treatment:

Drug: Binimetinib

Drug: PF-07284890

Expansion Phase (Part B Cohort 5)

Experimental group

Description:

PF-07284890 (at recommended dose from Part A) plus binimetinib in participants with BRAF V600 solid tumor; history of or current leptomeningeal metastases; without disease in the brain; with disease in the brain that does not meet Cohorts 1-4; asymptomatic or symptomatic in the brain; primary brain tumors

Treatment:

Drug: Binimetinib

Drug: PF-07284890

Expansion Phase Drug-Drug Interaction Substudy (Part B Optional Cohort 6)

Experimental group

Description:

PF-07284890 (at recommended dose from Part A) plus binimetinib plus midazolam in participants with BRAF V600 solid tumor

Treatment:

Drug: Binimetinib

Drug: PF-07284890

Drug: Midazolam

Expansion Phase (Part B Optional Cohort 7)

Experimental group

Description:

PF-07284890 (at the recommended dose for expansion when administered with food) plus binimetinib in participants with BRAF V600 solid tumor

Treatment:

Drug: Binimetinib

Drug: PF-07284890