Brigatinib and Binimetinib in Treating Patients With Stage IIIB-IV ALK or ROS1-Rearranged Non-small Cell Lung Cancer

NCT04005144 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 186517NCI-2019-02315
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of brigatinib and binimetinib in treating patients with stage IIIB-IV non-small cell lung cancer and a type of gene mutation called a rearrangement in the ALK or ROS1 genes. Brigatinib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

ALK Gene Rearrangement; Lung Non-Small Cell Carcinoma; Progressive Disease; ROS1 Gene Rearrangement; Stage IIIB Lung Cancer; Stage IIIC Lung Cancer; Stage IV Lung Cancer; Stage IVA Lung Cancer; Stage IVB Lung Cancer

Outcome Measures

Primary Outcomes (9)

• Recommended Phase 2 Dose

  Evaluating the number and frequency of adverse events as determined by the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version (v)5.0 by investigator's assessment will be used to determine the recommended phase 2 dose for future studies.

  Up to 12 months

• Number of Participants with Dose Limiting Toxicities

  A dose limiting toxicity (DLT) is generally defined as a grade 3 or higher, treatment-related adverse event that is attributable to the study treatment during the first 28 days of therapy (Cycle 1). The dose limiting toxicity will be based on the tolerability observed during cycle 1 of treatment/observation. Adverse events will be assessed by the investigators using NCI-CTCAE v5.0.

  Up to 28 days

• Number of Total Treatment-Emergent Adverse Events (AEs)

  Treatment Emergent AEs will be defined by the NCI CTCAE v5.0 as AEs newly occuring after the patient has begun study treatment.

  From treatment initiation through study completion, an average of 1 year

• Number of Treatment-Emergent Adverse Events by Grade

  Severity grade will be defined by the NCI CTCAE v5.0.

  From treatment initiation through study completion, an average of 1 year

• Number of Grade 3 or Greater Treatment-Emergent Adverse Events by CTCAE v5.0

  Severity grade will be defined by the NCI CTCAE v5.0.

  From treatment initiation through study completion, an average of 1 year

• Number of Serious Treatment-Emergent Adverse Events by CTCAE v5.0

  Severity grade will be defined by the NCI CTCAE v5.0.

  From treatment initiation through study completion, an average of 1 year

• Number of Treatment-Emergent Adverse Events with an Outcome of Death by CTCAE v5.0

  Severity grade will be defined by the NCI CTCAE v5.0.

  From treatment initiation through study completion, an average of 1 year

• Number of Treatment-Emergent Adverse Events Leading to Discontinuation of Study Treatment

  Severity grade will be defined by the NCI CTCAE v5.0.

  From treatment initiation through study completion, an average of 1 year

• Number of Treatment-Emergent Adverse Events Resulting in Interruption, Reduction, or Delay of study treatment

  Severity grade will be defined by the NCI CTCAE v5.0.

  From treatment initiation through study completion, an average of 1 year

Secondary Outcomes (5)

• Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  From treatment initiation through study completion, an average of 1 year

• Median Depth of Response Assessed by RECIST v1.1

  From treatment initiation through study completion, an average of 1 year

• Area Under the Plasma Concentration versus Time Curve (AUC) of Brigatinib

  At pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose on days 1 and 15 of cycle 1

• Median Progression Free Survival (PFS)

  Up to 6 months

• Median Overall Survival (OS)

  Up to 12 months

Study Arms (1)

Treatment (brigatinib, binimetinib)

EXPERIMENTAL

Patients receive brigatinib PO QD and binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Binimetinib; Drug: Brigatinib

Interventions

Binimetinib DRUG

Given PO

Also known as: ARRY-162, ARRY-438162, MEK162

Treatment (brigatinib, binimetinib)

Brigatinib DRUG

Given PO

Also known as: Alunbrig, AP 26113, AP-26113, AP26113

Treatment (brigatinib, binimetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytological confirmed stage IIIB/IV NSCLC
• Documented ALK-rearrangement (or ROS1- rearrangement) break-apart fluorescence in situ hybridization (FISH) (in \>= 15% or tumor cells), or next generation sequencing assay performed on tumor sample or cell free DNA in a Clinical Laboratory Improvement Act (CLIA)-approved laboratory
• At least one prior ALK or ROS1 targeted tyrosine kinase inhibitor (TKI). With progression or intolerance of most recent regimen
• Dose Escalation Phase Only: At least one prior ALK or ROS1 targeted TKI. With progression or intolerance of most recent regimen.

You may not qualify if:

• Measurable or evaluable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Age \>= 18 years
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Leukocytes \>= 3,000/microliter (mcL)
• Absolute neutrophil count \>=1,500/mcL
• Platelets \>= 75,000/mcL
• Hemoglobin (Hgb) \>= 9 gm/dL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) =\< 5 x institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 5 x institutional upper limit of normal if there are liver metastases
• Creatinine within normal institutional limits OR
• Creatinine clearance \>= 50 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal
• Female participants who:
• Are postmenopausal for at least 1 year before the screening visit, OR

Sponsors & Collaborators

• University of California, San Francisco: lead
• Takeda: collaborator
• Array BioPharma: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Disease Progression; Lung Neoplasms

Interventions

binimetinib; brigatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Collin Blakely, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2019
• First Posted: July 2, 2019
• Study Start: February 25, 2020
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: October 17, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)