Brigatinib Plus Chemotherapy or Local Consolidation Therapy in ALK Positive Advanced Non-small Cell Lung Cancer (BrightStar-2)

NCT06522360 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2024-0130NCI-2024-06173
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical research study is to learn if the combination of brigatinib and either local consolidation therapy (such as radiotherapy or surgery) or chemotherapy (pemetrexed and carboplatin) can help to control the disease compared with brigatinib alone. The safety of these combinations will also be studied.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (3)

Brigatinib Monotherapy

EXPERIMENTAL

Given by mouth

Drug: Brigatinib

Brigatinib + Carboplatin + Pemetrexed

EXPERIMENTAL

Given by vein

Drug: Brigatinib; Drug: Carboplatin; Drug: Pemetrexed

Brigatinib + Local Consolidation Therapy (LCT)

EXPERIMENTAL

Given by vein

Drug: Brigatinib

Interventions

Brigatinib DRUG

Given by mouth

Also known as: Alunbrig

Brigatinib + Carboplatin + Pemetrexed; Brigatinib + Local Consolidation Therapy (LCT); Brigatinib Monotherapy

Carboplatin DRUG

Given by mouth

Brigatinib + Carboplatin + Pemetrexed

Pemetrexed DRUG

Given by vein

Brigatinib + Carboplatin + Pemetrexed

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of stage IV NSCLC (or recurrent NSCLC not a candidate for definitive multimodality therapy)
• Documented ALK re-arrangement as detected by: (1) FISH, (2) IHC, (3) tissue NGS, or (4) cfDNA NGS
• Subjects can be enrolled as (a) TKI naïve or (b) after/during 12 weeks of first line brigatinib treatment without disease progression or (c) after 4 weeks of first line alectinib, lorlatinib or ensartinib treatment without disease progression, those patients must be switched to brigatinib.
• Candidate for local consolidation therapy in the opinion of the treating physician.
• \. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 6. Males or females ≥ 18 years. Because no dosing or adverse event data are currently available on the use of brigatinib in combination with other agents in patients \<18 years of age, children are excluded from this study.
• \. Adequate organ function laboratory values, defined as:
• a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L or at least 1500/mm3 or at least 1.5 x 109/L b. Platelet count at least 75,000/mm3 or at least 75 x 109/L c. Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline d. Serum creatinine ≤ 1.5 × ULN or ≥ 60 mL/minute for subjects with creatinine clearance levels \> 1.5 × the institutional ULN e. Serum total bilirubin less than or equal to ≤ 1.5 × ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 × ULN f. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN except for subjects with liver metastases for whom ALT and AST should be ≤ 5× ULN g. International Normalized Ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy if PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants h. Activated PTT (aPTT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulant 8. Female patients of childbearing potential must have a negative pregnancy test documented at time of screening.
• \. Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to use a highly effective method of contraception from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.
• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
• History of bilateral tubal ligation or another surgical sterilization procedure.

You may not qualify if:

• \. Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who have had at least 2 years elapsed since the completion of radical treatment and the adjuvant therapy, if any, of the other primary malignancy.
• \. Previously received more than 1 cycle of chemotherapy +/-immunotherapy for locally advanced or metastatic disease.
• \. Symptomatic CNS metastasis. Asymptomatic CNS disease requiring increasing dose of corticosteroids within 7 days prior to study enrollment is also not permitted.
• \. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed.
• \. The presence of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis at screening.
• \. Have a known or suspected hypersensitivity to brigatinib or its excipients. 8. Have malabsorption syndrome or other gastrointestinal (GI) illness or condition that could affect oral absorption of the study drug.
• \. Have uncontrolled hypertension. Patients with hypertension as defined by current standard of practice should be under treatment on study entry to control blood pressure.
• \. Received radiation therapy within 14 days before randomization except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
• \. Had major surgery within 30 days of enrollment. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.
• \. Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to the following: a) Myocardial infarction within 6 months before enrollment. b) Unstable angina within 6 months before enrollment. c) New York Heart Association Class III or IV heart failure within 6 months before enrollment. d) History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician. e) Any history of clinically significant ventricular arrhythmia.
• \. Had a cerebrovascular accident within 6 months before first dose of study drug.
• \. Have an ongoing or active infection, including the requirement for intravenous antibiotics.
• \. Subjects should not receive other anti-cancer agents (e.g., chemotherapy, immunotherapy, biologic therapy, and/or hormone therapy other than for replacement or appetite stimulant) while on treatment in this study.
• \. History of allergic reactions attributed to compounds of similar chemical or biologic composition to brigatinib, carboplatin and pemetrexedor other agents used in study.
• \. Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

brigatinib; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Yasir Y Elamin, MD

  MD Anderson Cancer Cetner

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: July 26, 2024
• Study Start: December 11, 2024
• Primary Completion: April 17, 2025
• Study Completion: April 17, 2025
• Last Updated: April 24, 2025

Record last verified: 2025-04