Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants with Advanced or Refractory Tumors

MapKure

Status and phase: Active, not recruiting; Phase 1

Conditions: Solid Tumor; B-Raf Mutation-Related Tumors

Treatments: Drug: BGB-3245

Study type: Interventional

Funder types: Industry

Identifiers

NCT04249843

BGB-3245-AU-001

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, and antitumor activity of BGB-3245 in participants with advanced or refractory solid tumors

Enrollment: 110 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Participants with histologically confirmed advanced or metastatic solid tumor who had disease progression during or after systemic anticancer therapies that previously demonstrated clinical benefit (eg, improved survival) in a representative population, or are unable to receive standard therapy(ies). In addition, participants must meet the following eligibility criteria for the corresponding phase of the study:

   1. Phase 1a: participants with a known mutation status and tumor harboring an oncogenic mutation of the v-RAF murine sarcoma viral oncogene homolog B (BRAF) gene (the mutations of primary interest are the BRAF Class II mutation, Class III mutation or BRAF fusion). In addition, participants with tumors harboring the mutation of the neuroblastoma RAS viral oncogene homolog (NRAS) gene or the Kirsten rat sarcoma virus oncogene homolog (KRAS) are eligible for Part 1a. For participants with KRAS mutations, tumor types of colorectal cancer (CRC) and pancreatic cancer are excluded.
   2. Phase 1b: participants must have a known mutation status and meet one of the following criteria according to the group they are enrolled into:

   I. Group 1: participants with tumor types other than CRC that harbor BRAF V600 mutations who have been treated and progressed on prior BRAF and/or mitogen activated protein kinase (MEK) inhibition.

   II. Group 2: participants with advanced solid tumors harboring a BRAF Class II mutation or a BRAF fusion mutation.

   III. Group 2 BRAF Fusion Expansion: Participants with advanced solid tumors harboring a BRAF fusion mutation

2. Participants must provide archival tumor tissue or agree to a fresh tumor biopsy for mutation and biomarkers analysis (fresh tumor biopsies are strongly recommended)

3. Participants must have radiologically measurable disease as defined by RECIST v1.1

4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1

5. Adequate organ function and no transfusions within 14 days of first dose

Key Exclusion Criteria :

1. Participants receiving cancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the time of Cycle 1 Day 1.

2. All participants who have received prior systemic anticancer treatment within the following time frames will be excluded:

   1. Systemic chemotherapy within 4 weeks or 6 weeks for nitrosourea, mitomycin prior to Cycle 1 Day 1; and
   2. Biologic therapy (i.e., antibodies), continuous or intermittent small-molecule therapies, or any other investigational agents within a period of 5 times the half-life of the agent or ≤4 weeks (whichever is shorter) prior to Cycle 1 Day 1.

3. Severe or uncontrolled systemic disease.

4. Clinically significant cardiac disease within 6 months of signing the ICF

5. CNS metastases, leptomeningeal carcinomatosis or untreated spinal cord compression.

6. Any unstable, preexisting major medical condition, including known human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

7. Systemic anti-cancer therapy within 2 weeks or 5 half-lives before first dose.

8. Major surgical procedure or significant traumatic injury within 4 weeks prior to the first dose or anticipates need for major surgery while on study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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110 participants in 2 patient groups

Phase 1a: Dose Escalation

Experimental group

Description:

BGB-3245 administered orally (PO)

Treatment:

Drug: BGB-3245

Phase 1b, Group 1: Dose Expansion

Experimental group

Description:

BGB-3245 administered orally (PO)

Treatment:

Drug: BGB-3245