Phase 1/2 Study of the Safety and Efficacy of Rociletinib in Combination With Trametinib in Patients With mEGFR-positive Advanced or Metastatic Non-small Cell Lung Cancer

• Status: Terminated
• Trial end date: 2016-06-27
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib when administered in combination with trametinib.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Clovis Oncology, Inc.
• Collaborator: Novartis Pharmaceuticals
• Treatments: Trametinib

Criteria

Inclusion Criteria:

• Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation

• Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1

• Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI

• Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2)

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months

• Adequate hematological and biological function; LVEF ≥50%

Exclusion Criteria:

• Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification

• Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks)

• Known preexisting interstitial lung disease or pneumonitis

• Concurrent use of QT-prolonging medication

• Uncontrolled diabetes (HA1C > 10%) despite optional therapy

• Cardiac abnormalities:

• Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms

• Inability to measure QT interval on ECG

• Personal or family history of long QT syndrome

• Implantable pacemaker or implantable cardioverter defibrillator

• Resting bradycardia < 55 beats/min

• Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment

• Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy)

• Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment

• Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients