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

About this trial

Last updated 8 years ago

Study ID

CO-1686-033

Status

Terminated

Type

Interventional

Phase

Phase 1

Placebo

Accepting

18+ Years

All Sexes

Trial Timing

Ended 10 years ago

What is this trial about?

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

What are the participation requirements?

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