A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors

• Status: Recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of PLX8394.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fore Biotherapeutics; Plexxikon

Criteria

Inclusion Criteria- Group A:

• Age ≥ 12 years and at least 40 kg.

• Phase 1-Dose Escalation (no longer enrolling as of Protocol Amendment 10): Patients with histologically confirmed advanced solid tumors who are refractory to, relapsed after, or intolerant to standard therapy or for whom no standard therapy exists.

• Phase 2a-RP2D Confirmation/Redefinition (Formulation 2) and Phase 2a-Dose Extension:

Patients with a history of histologically confirmed solid tumors with a BRAF mutation. Following RP2D confirmation and redefinition, extension subjects must meet criteria for Cohort 1 and Cohort 2 as specified below:

• Phase 2a-Dose Extension-Cohort 1

1. Patients with solid tumors (as of Amendment 10, only subjects with glioma tumors) driven by a BRAF-V600 mutation

2. Patients with no prior exposure to BRAF-directed therapy and for whom no standard therapy exists.

• Phase 2a-Dose Extension-Cohort 2

1. Patients with solid tumors driven by BRAF non-V600 mutation.

2. Patients with prior exposure to BRAF-directed therapy will be allowed, pending confirmation of mutations in either a re-biopsy or ctDNA, if the mutational profile identifies a potential for response based on PLX8394 mechanism of action and after investigator discussion.

• Measurable disease by RECIST 1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• Adequate hematologic, hepatic, and renal function.

• Women of child-bearing potential must have a negative pregnancy test and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study drug. Women of non-child-bearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥ 1 year.

• Fertile men must agree to use an effective method of birth control during the study and for up to 3 months after the last dose of study drug.

• Completion of previous anti-cancer therapy at least 2 weeks before study drug initiation.

Exclusion Criteria- Group A:

• Phase 1 and Phase 2a RP2D confirmation-Dose Escalation: Investigational drug use within 28 days (or 5 half-lives, whichever is shorter) of the first dose of PLX8394.

• Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating study drug or anticipation of the need for major surgery during the study.

• Uncontrolled intercurrent illness.

• Patients with colorectal cancer or pancreatic cancer

• Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Medical Monitor. Patients with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.

• Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.

• Clinically significant cardiac disease.

• Known infection with HIV, HBV, or HCV or a known carrier of HBV or HCV.