Non-Small Cell Lung Cancer
Conditions
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of this investigational drug, brigatinib (AP261136) in patients with advanced non-small cell lung cancer Non-small cell lung cancer (NSCLC) who have had first-line treatment for their cancer and it still got worse, even after, or while taking drugs called ALK inhibitors, or anti-cancer drugs that act on tumors. Some examples of these anti-cancer drugs are: KEYTRUDA® or ALECENSA®).
Detailed description
A significant population of Anaplastic Lymphoma Kinase (ALK) plus Non-small cell lung cancer patients exist that have progressed on or who were intolerant of second generation anaplastic lymphoma kinase inhibitor (e.g. ceritinib or alectinib). Brigatinib has demonstrated activity in patients who have progressed on crizotinib, but the activity of brigatinib in patients who have progressed on ceritinib, alectinib, or other second generation anaplastic lymphoma kinase inhibitors is unknown. Based on the preclinical data. 3, , brigatinib has activity against known secondary anaplastic lymphoma kinase mutations suggesting it may retain activity after second-generation anaplastic lymphoma kinase inhibitors. Patients enrolled in ARI-AT-002 must have previously received a second generation Anaplastic lymphoma kinase inhibitor other than brigatinib. We have chosen 20% as a clinically meaningful response rate that would justify further study of brigatinib in previously treated anaplastic lymphoma kinase plus disease.
Interventions
DRUGbrigatinib
Single arm phase 2 trial to investigate the clinical activity in patients with advanced non-small cell lung cancer
Sponsors
University of Colorado, Denver
Duke University
Takeda
Vanderbilt University
University of Texas Southwestern Medical Center
University of Pittsburgh
Ohio State University
Georgetown University
Academic Thoracic Oncology Medical Investigators Consortium
Criterium, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Locally advanced or metastatic NSCLC that has been cytologically or histologically confirmed ALK rearrangement based on FDA approved test (e.g. Vysis breakapart FISH or IHC using Ventana) ECOG PS ≤2 Age of ≥ 18 years Brain lesions may be used as target lesions if progressing, ≥10mm in longest diameter and if they were not previously treated with any of the following: * Whole brain radiation therapy (WBRT) within 3 months * Stereotactic radiosurgery (SRS) * Surgical resection Availability of core biopsy of progressive lesion taken within 60 days prior to D1 of treatment under study therapy or willing to undergo tumor biopsy: NOTE:. All subjects must consent to provide tumor blocks or slides. * If archival tissue is not available and biopsies to obtain fresh tumor tissue cannot be performed with minimal risk to the subject, subjects may be permitted to enroll on the study with prior approval of the Study PI. * In the situation the patient undergoes biopsy within 60 days prior to D1. and there is insufficient tumor tissue subjects for the correlative science part of the protocol patient will be permitted to enroll on the study with prior approval of the study PI * In the situation the patient undergoes molecular testing or next-generation sequencing as part of standard care there must be sufficient tumor sample available for participation in the study (i.e. a next generation sequencing report is not sufficient for enrollment) Recovered from toxicities related to prior anticancer treatment to ≤Grade 2 or baseline with the exception of alopecia Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in females Adequate organ function defined as: Absolute neutrophil count (ANC) ≥1500/µL Platelets ≥75,000/µL Hemoglobin≥ 10g/dL AST /ALT ≤ 2.5 x upper limit of normal (ULN); ≤ 5 x ULN if liver metastasis Total serum bilirubin ≤ 1.5 x ULN Serum creatinine ≤ 1.5 x UNL Serum amylase ≤ 1.5 x UNL At least 1 measurable lesion per RECIST version 1.1 Negative serum pregnancy test within 7 days of D1 of treatment in women of child bearing potential (WOCBP) If fertile, willing to use highly effective form of contraception (defined as a combination of at least two of the following methods: condom or other barrier methods, oral contraceptives, implantable contraceptives, intrauterine devices) during the dosing period and for at least 4 months after Ability to provide signed informed consent and willing and able to comply with all study requirements Inclusion criteria for cohort assignment: Cohort A: Progressive disease on any next generation ALK inhibitor except first line alectinib or brigatinib (any line) Cohort B: Progressive disease on first-line therapy with alectinib, and no other ALK inhibitors Cohort C: Previous treatment brigatinib at 180 mg daily for ≥4 weeks without \> grade 2 drug-related toxicities and with radiographic evidence of progressive disease and no intervening systemic therapies such as chemotherapy, immunotherapy or another ALK inhibitor (radiation therapy allowed as intervening therapy). Patients who are treated on cohorts A and B will be allowed to enroll in cohort C if the meet the inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Through study completion (average 42 months) | An assessment of the response using RECIST 1.1 per investigator. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.. The enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results |
Countries
United States
Participant flow
Recruitment details
Study closed before total enrollment expectations were met.
Pre-assignment details
The clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results. Patient were enrolled in the trial and were assigned based on previous treatment
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Disease Progression After Next Generation ALK TK Patients could enroll in this cohort after a next generation ALK TKI (regardless of the number of previous therapies) | 27 |
| Cohort B: Disease Progression After Alectinib as First-line Therapy Patients could enroll in this cohort after first-line alectinib | 4 |
| Arm C: Brigatinib 240 mg for Patients With Disease Progression on Brigatinib Patients who tolerated standard dose brigatinib and had disease progression could enroll in this cohort | 1 |
| Total | 32 |
Baseline characteristics
| Characteristic | Cohort A: Disease Progression After Next Generation ALK TK | Cohort B: Disease Progression After Alectinib as First-line Therapy | Arm C: Brigatinib 240 mg for Patients With Disease Progression on Brigatinib | Total |
|---|---|---|---|---|
| Age, Customized Median Age | 57 years | 43 years | 76 years | 56 years |
| Race/Ethnicity, Customized African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Latino or Hispanic | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 23 Participants | 3 Participants | 1 Participants | 27 Participants |
| Sex: Female, Male Female | 11 Participants | 1 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 16 Participants | 3 Participants | 1 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 27 | 1 / 4 | 1 / 4 |
| other Total, other adverse events | 11 / 27 | 1 / 4 | 1 / 4 |
| serious Total, serious adverse events | 8 / 27 | 2 / 4 | 2 / 4 |
Outcome results
Primary
Objective Response Rate
An assessment of the response using RECIST 1.1 per investigator. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.. The enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results
Time frame: Through study completion (average 42 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Brigatinib After Next Generation ALK TKI Regardless of Number of Therapies | Objective Response Rate | 9 Participants |
| Arm B: Brigatinib After First-line Therapy With Alectinib | Objective Response Rate | 1 Participants |
| Arm C: Brigatinib 240 mg in Patient With Disease Progression on Brigatinib 180 mg Daily | Objective Response Rate | 0 Participants |