A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients with BRAFV600-mutant Non-small Cell Lung Cancer
- Conditions
- BRAFV600 mutant NSCLClung cancer with a specifc mutation1003866610029107
- Registration Number
- NL-OMON54680
- Lead Sponsor
- Array Biopharma Inc. (a wholly owned subsidiary of Pfizer Inc.)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 25
Patients must meet all of the following criteria to be eligible for enrollment
in the study:
1. Able to provide written informed consent. Adult patients under guardianship
may participate with the consent of their legally authorized guardian if
permitted by local regulations.
2. Age >= 18 years at the time of informed consent.
3. Histologically confirmed diagnosis of NSCLC that is currently Stage IV (M1a,
M1b, M1c- AJCC 8th edition).
4. Presence of a BRAFV600E mutation in tumor tissue or blood (e.g., ctDNA
genetic testing) as determined by a local laboratory assay. Other Class 1
BRAFv600 mutations (e.g., K or D) will be permitted with prior discussion with
the Sponsor.
5. The Investigator must obtain prior to enrollment that the patient has
adequate tumor tissue for submission to a central laboratory for confirmation
of BRAFV600 mutation status.
6. Patients who are either treatment-naïve (e.g., no prior systemic therapy for
advanced/metastatic disease), OR who have received 1) first-line platinum-based
chemotherapy OR 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given
alone or in combination with platinum-based chemotherapy, or in combination
with immunotherapy (e.g., ipilimumab) with or without given alone or in
combination with platinum-based chemotherapy.
7. Presence of measurable disease based on RECIST v1.1.
8. ECOG performance status of 0 or 1.
9. Adequate bone marrow function characterized by the following at screening:
a. ANC >= 1.5 × 109/L;
b. Platelets >= 100 × 109/L;
c. Hemoglobin >= 8.5 g/dL (with or without blood transfusions).
10. Adequate hepatic and renal function characterized by the following at
screening:
a. Total bilirubin <= 1.5 × ULN
b. ALT and AST <= 2.5 × ULN, or <= 5 × ULN in presence of liver metastases;
c. Serum creatinine <= 1.5 × ULN; or calculated creatinine clearance
>= 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate
> 50 mL/min/1.73m2.
11. Able to swallow, retain and absorb oral medications.
12. Willingness and ability to comply with scheduled visits, treatment plan,
laboratory tests and other study procedures.
13. Female patients of childbearing potential, must have a negative serum β-HCG
test result.
14. Female patients of childbearing potential must agree to use methods of
contraception that are highly effective or acceptable and to not donate ova
from Screening until 30 days after the last dose of study treatment.
15. Male patients must agree to use methods of contraception that are highly
effective or acceptable, and to not donate sperm from Screening until 90 days
after the last dose of study drug.
Patients meeting any of the following criteria are ineligible for enrollment in
the study.
1. Patients who have documentation of any of the following: EGFR mutation, ALK
fusion oncogene or ROS1 rearrangement.
2. Patients who have received more than 1 prior line of systemic therapy in the
advanced/metastatic setting. Prior therapies can be reviewed with the Array
Medical Monitor.
3. Previous treatment with any BRAF inhibitor (e.g., dabrafenib, vemurafenib,
XL281/BMS-908662, etc.), or any MEK inhibitor (e.g., trametinib, cobimetinib,
selumetinib, RDEA119, etc.) prior to screening and enrollment.
4. Receipt of anticancer medications or investigational drugs within the
following intervals before the first administration of study treatment:
a. <= 14 days for chemotherapy, targeted small-molecule therapy, radiation
therapy, immunotherapy, or antineoplastic biologic therapy (e.g., erlotinib,
crizotinib, bevacizumab, etc.).
b. <= 14 days or 5 half-lives (minimum of 14 days) for investigational agents or
devices. For investigational agents with long half-lives (e.g., > 5 days),
enrollment before the fifth half-life requires medical monitor approval.
c. Palliative radiation therapy must be complete 7 days prior to the first dose
of
study treatment.
5. Patients who have had major surgery (e.g., inpatient procedure with regional
or general anesthesia) <= 6 weeks prior to start of study treatment.
6. Patient has not recovered to <= Grade 1 from toxic effects of prior therapy
and/or complications from prior surgical intervention before starting study
treatment.
7. Current use of a prohibited medication (including herbal medications,
supplements or foods) or use of a prohibited medication <= 1 week prior to
the start of study treatment.
8. Impairment of gastrointestinal function or disease which may significantly
alter the absorption of oral study treatment (e.g., uncontrolled nausea,
vomiting or diarrhea, malabsorption syndrome, small bowel resection).
9. Impaired cardiovascular function or clinically significant cardiovascular
diseases, including any of the following:
a. History of acute myocardial infarction, acute coronary syndromes (including
unstable angina, coronary artery bypass graft, coronary angioplasty or stenting)
<= 6 months prior to start of study treatment;
b. Congestive heart failure requiring treatment (New York Heart Association
Grade >= 2);
c. LVEF < 50% as determined by MUGA or ECHO;
d. Uncontrolled hypertension defined as persistent systolic blood pressure
>= 150 mmHg or diastolic blood pressure >= 100 mmHg despite optimal therapy;
e. History or presence of clinically significant cardiac arrhythmias (including
uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular
tachycardia);
f. Triplicate average baseline QTcF interval >= 480 ms or a history of prolonged
QT
syndrome.
10. History of thromboembolic or cerebrovascular events <= 12 weeks prior to the
first dose of study treatment. Examples include transient ischemic attacks,
cerebrovascular accidents, hemodynamically significant (i.e. massive or
sub-massive) deep vein thrombosis or pulmonary emboli.
11. History or current evidence of RVO or current risk factors for RVO (e.g.,
uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or
hypercoagulability syndromes
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint:<br /><br>ORR defined as the proportion of patients who have achieved a confirmed best<br /><br>overall response (CR or PR) as determined by Investigator review of<br /><br>radiographic disease assessments per RECIST v1.1 both in the treatment-naïve<br /><br>setting and in previously treated setting.</p><br>
- Secondary Outcome Measures
Name Time Method