Clinical trial NCT02630186: A Phase 1b/2 Study of Safety and Efficacy of Rociletinib in Combination With MPDL3280A in Patients With Advanced or Metastatic EGFR-mutant NSCLC
Official title: A Phase 1b/2 Study of the Safety and Efficacy of Rociletinib (CO-1686) Administered in Combination With MPDL3280A in Patients With Activating EGFR Mutation-positive (EGFRm) Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Clovis Oncology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2015-12-15
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This clinical research study is being carried out in two parts, Phase 1 and Phase 2. The primary purpose of the Phase 1 portion of the study is to observe the safety of the combination of rociletinib and MPDL3280A in EGFR-mutant NSCLC patients.

The primary purpose of the Phase 2 portion of the study is to evaluate the safety and anti-tumor effects of the combination of rociletinib and MPDL3280A, at the best doses for the combination determined in Phase 1, in patients with EGFR-mutant NSCLC.

Detailed description: This is a Phase 1b/2, open-label, non-randomized, multicenter study evaluating the safety and efficacy of rociletinib administered in combination with MPDL3280A.

Phase 1: This will be the dose finding phase of the study. Patients will be enrolled to available Dosing Cohort. Patients who have progressed after prior first- or second-generation EGFR TKI, regardless of T790M mutation status, will be enrolled.

Phase 2: Patients will be enrolled into 2 groups. Group A will enroll eligible first-line patients who are EGFR TKI treatment-naïve and chemotherapy-naïve. Group B will enroll eligible patients who have progressed after prior first- or second-generation EGFR TKI, regardless of T790M mutation status.

Eligibility criteria: Inclusion Criteria:

* ECOG performance status of 0 or 1
* Adequate hematological and biological function, confirmed by defined laboratory values
* Histologically or cytologically documented metastatic or unresectable, locally advanced or metastatic NSCLC, with one or more activating EGFR mutation (eg, G719X, exon 19 deletion, L858R, L861Q) and absence of exon 20 insertion
* Measurable disease as defined by RECIST v1.1
* Biopsy of tumor tissue for central evaluation, within 60 days prior to the first day of study treatment
* For Phase 1 and Phase 2 Group B, progression after prior 1st or 2nd generation EGFR TKI (eg, erlotinib, gefitinib, afatinib). Previous chemotherapy for NSCLC is allowed.
* For Phase 2 Group A, EGFR TKI treatment-naïve and chemotherapy-naïve

Exclusion Criteria:

* Unresolved toxicities from prior therapy
* Symptomatic, untreated or unstable central nervous system or leptomeningeal metastases
* Previous treatment with rociletinib or MPDL3280A, or other 3rd generation EGFR TKI (eg, AZD-9291, HM61713), or PD 1 axis targeted therapy (eg, anti PD 1 or anti-PD L1)
* Prior treatment with CD137 agonists or other immune checkpoint blockade therapies, including anti-CTLA-4 therapeutic antibodies
* Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures
* Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab (bisphosphonate use for prevention of skeletal events allowed)
* Known hypersensitivity to any component of the MPDL3280A or rociletinib formulations or history or hypersensitivity to chimeric humanized antibodies or fusion proteins
* History of autoimmune disease
* History of prior allogeneic hematopoietic stem cell transplantation or prior solid organ transplantation
* Treatment with systemic immunosuppressive medications within 2 weeks prior to first day of study treatment (inhaled corticosteroids and mineralocorticoids allowed)
* Live attenuated vaccine within 4 weeks prior to first day of study treatment
* Active tuberculosis, active hepatitis, or positive HIV status
* Class II to IV heart failure as defined by the New York Heart Association functional classification system
* Untreated or uncontrolled cardiovascular disease or other symptomatic cardiac dysfunction
* QTCF \> 450 ms, inability to measure QT interval on ECG, personal or family history of long QT syndrome, requirement for medications that have the potential to prolong the QT interval
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan (history of radiation pneumonitis in radiation field may be allowed)
* Other malignancies within 5 years prior to enrollment, with the exception of carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ

Primary outcomes:
measure: Number of Treatment-emergent Adverse Events, as Assessed by NCI CTCAE v4.03
timeFrame: Continuously, up to approximately 18.5 months
measure: Maximum Concentration (Cmax) of Rociletinib and Its Metabolites
timeFrame: Treatment Day 1 and Day 15
measure: Time to Maximum Concentration (Tmax) for Rociletinib and Rociletinib Metabolites
timeFrame: Treatment Day 1 and Day 15
measure: Minimum Concentration (Cmin) of Rociletinib and Metabolites
timeFrame: Approximately every 6 weeks up to 24 months
measure: Area Under the Curve (AUC) of Rociletinib and Rociletinib Metabolites
timeFrame: Treatment Day 1 and Day 8
measure: Maximum Concentration (Cmax) of MPDL3280A
timeFrame: Cycle 1 Day 1
measure: Minimum Concentration (Cmin) of MPDL3280A
timeFrame: Approximately every 6 weeks up to 24 months
measure: Objective Response Rate Per RECIST v1.1 in Phase 2
timeFrame: Approximately every 6-9 weeks
Secondary outcomes:
measure: Objective Response Rate Per Modified RECIST v1.1, Incorporating Immune-related Criteria, in Phase 2
timeFrame: Approximately every 6-9 weeks, up to 24 months
measure: Duration of Response Per RECIST v1.1 and Modified RECIST v1.1, Incorporating Immune-related Criteria, in Phase 2
timeFrame: Approximately every 6-9 weeks, up to 24 months
measure: Progression-free Survival Per RECIST v1.1 and Modified RECIST v1.1, Incorporating Immune-related Criteria, in Phase 2
timeFrame: Approximately every 6-9 weeks, up to 24 months
measure: Number of Patients Alive at Study Termination
timeFrame: Up to approximately 18.5 months
measure: Longitudinal Changes in Blood Based Biomarkers (eg, Mutations in EGFR) in ctDNA
timeFrame: Blood samples will be collected from each patient approximately every 3 weeks, up to 24 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: University of California at Los Angeles
state: California
Study officials:
affiliation: Clovis Oncology, Inc.
name: Lindsey Rolfe, MD
role: STUDY_DIRECTOR
References: