A study comparing combination of Encorafenib + Binimetinib in Patients with BRAF V600E-mutant Non-small Cell Lung Cancer.

Phase 1

• Conditions: BRAF V600E-mutant Non-small Cell Lung Cancer; MedDRA version: 20.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000417-37-ES
• Lead Sponsor: Array BioPharma Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-11
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

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 or M1b- AJCC 7th edition).
4. Presence of a BRAFV600E mutation in lung cancer tissue as determined by a local laboratory assay.
5. The Investigator must confirm prior to enrollment that the patient has adequate tumor tissue available to confirm BRAFV600E mutation status by central laboratory.
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.
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 as described in Appendix 1, must have a negative serum ß-HCG test result. 14. Female patients of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, as described in Appendix 1, 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, as described in Appendix 1, and to not donate sperm from Screening until 90 days after the last dose of study drug.
14. Female patients of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, as described in Appendix 1, 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, as described in Appendix 1, and to not donate sperm from Screening until 90 days after the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion Criteria

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.
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), as described in Section 6.5.2, 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); history of retinal degenerative disease.
12. Concurrent neuromuscular disorder that is associated with the potential of elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
13. Evidence of active, noninfectious pneumonitis, history of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified