Description:
The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib when administered in combination with trametinib.
Clinical Trials /
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
NCT02580708
Related Conditions:
- Non-Small Cell Lung Carcinoma
Recruiting Status:
Terminated
Phase:
Phase 1/Phase 2
Trial Eligibility
Document
Title
Clinical Trial IDs
NCT ID: NCT02580708
ORG ID: CO-1686-033
Trial Conditions
Non-small Cell Lung Cancer
Trial Interventions
| Drug | Synonyms | Arms |
|---|---|---|
| Rociletinib | CO-1686 | Rociletinib and Trametinib |
| Trametinib | Mekinist | Rociletinib and Trametinib |
Trial Purpose
The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib
when administered in combination with trametinib.
Detailed Description
This is a Phase 1/2, open-label, non randomized, multicenter study evaluating the safety and
efficacy of rociletinib administered in combination with trametinib.
This study will be conducted in 2 phases:
Phase 1: This will be the dose escalation phase of the study. Phase 1 will determine the MAD
or MTD and RP2D of the combination of rociletinib and trametinib, and evaluate its safety
and tolerability and PK profile in EGFRm NSCLC patients who have failed at least one prior
EGFR TKI.
Phase 2: This will be the dose expansion phase. Phase 2 will evaluate the preliminary
efficacy and pharmacodynamics of the combination of rociletinib and trametinib at the RP2D
in two subsets of EGFRm NSCLC patients.
Trial Arms
| Name | Type | Description | Interventions |
|---|---|---|---|
| Rociletinib and Trametinib | Experimental | Rociletinib, Trametinib |
Eligibility 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
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Primary Outcome Measures
Incidence of treatment-emergent adverse events
Objective Response Rate (ORR)
Cmax of rociletinib and trametinib at steady state
Tmax of rociletinib and trametinib at steady state
AUC of rociletinib and trametinib at steady state
Cmin of rociletinib and trametinib at steady state
t1/2 of rociletinib at steady state
Secondary Outcome Measures
Duration of Response (DR) According to RECIST Version 1.1
Disease Control Rate (DCR) According to RECIST Version 1.1
Progression Free Survival (PFS) According to RECIST Version 1.1
Overall Survival (OS)
Longitudinal changes in blood based biomarkers (i.e. mutations in EGFR) in ctDNA
Cmax of rociletinib metabolites at steady state
Tmax of rociletinib metabolites at steady state
AUC of rociletinib metabolites at steady state
Cmin of rociletinib metabolites at steady state
