Non-small Cell Lung Cancer
Conditions
Brief summary
Phase 2 multicenter, controlled, randomized, double-blind study to evaluate the efficacy and safety of ficlatuzumab versus placebo when administered with erlotinib in subjects with previously untreated metastatic EGFR-mutated NSCLC and BDX004 Positive Label.
Detailed description
This is a Phase 2 multicenter, controlled, randomized, double-blind study to evaluate the efficacy and safety of ficlatuzumab versus placebo when administered with erlotinib in subjects with previously untreated metastatic EGFR-mutated NSCLC and BDX004 Positive Label. Prior to screening, subjects will have tested positive for a sensitizing EGFR mutation to determine eligibility for treatment with erlotinib. During screening, subject serum samples will be tested using the investigational companion diagnostic (BDX004) test. Only those subjects who have a BDX004 Positive Label will be enrolled. Subject randomization will be stratified by EGFR mutation type and smoking status (ever versus never smokers). Subjects will be designated as never smokers if they have smoked less than 100 cigarettes in their lifetime. Radiographic tumor assessment, to include CT or MRI of chest and abdomen, will be performed every 4 weeks for the first 8 cycles, and every 8 weeks thereafter, using the same imaging modality per subject. Safety assessments will be performed on an ongoing basis.
Interventions
Sponsors
Biodesix, Inc.
AVEO Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically and/or cytologically confirmed primary diagnosis of Stage IV NSCLC (according to American Joint Committee on Cancer \[AJCC\] 7th edition lung cancer staging criteria). * Measurable disease according to RECIST v.1.1. * An EGFR exon 19 deletion and/or an exon 21 (L858R) substitution mutation. * BDX004 Positive Label. * Have received no prior systemic chemotherapy, immunotherapy, targeted therapy, or biologic therapy for metastatic NSCLC. Subjects may have previously been treated with postoperative adjuvant chemotherapy for early stage lung cancer or chemo radiotherapy for locally advanced disease provided this was completed at least 6 months prior to enrollment. No prior EGFR TKI therapy is allowed for any stage of NSCLC. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion criteria
* History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or erlotinib. * History of known brain metastases. * Prior treatment with any other investigational drug or biologic agent within 5 half lives prior to randomization, or any investigational device within 2 weeks prior to randomization. * Any unresolved toxicity from previous radiation therapy. * Significant cardiovascular disease, including: * Echocardiogram (ECHO) or multiple gated acquisition (MUGA) showing left ventricular ejection fraction of less than 55%. * Cardiac failure New York Heart Association class III or IV. * Myocardial infarction, severe or unstable angina within 6 months prior to randomization. * History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation). * Significant thrombotic or embolic events within 3 months prior to randomization (significant thrombotic or embolic events include but are not limited to stroke or transient ischemic attack). * Any uncontrolled or severe cardiovascular disease. * History of prior malignancy within 3 years prior to randomization (except for adequately treated non-melanoma skin cancer, carcinoma in situ of the breast or cervix, superficial bladder cancer, or early stage prostate cancer, without evidence of recurrence). * Radiographic evidence of interstitial lung disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Approximately 24 months | Progression Free Survival is defined as the time from the date of randomization to the date of the first objective documentation of radiographic disease progression or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Approximately 24 months | To evaluate Safety and tolerability of ficlatuzumab plus erlotinib versus placebo plus erlotinib in subjects who have previously untreated metastatic EGFR-mutated NSCLC and a BDX004 Positive Label. |
Countries
Australia, Hong Kong, Italy, Singapore, South Korea, Taiwan, United States
Participant flow
Recruitment details
Subjects who met all the inclusion and none of the exclusion criteria were enrolled in 9 sites in the United States, Australia, Hong Kong, Italy, Singapore, Korea, and Taiwan. The Sponsor terminated Study AV-299-14-206, effective 14-Sep-2016, after determining that enrollment of participants was much lower than expected.
Pre-assignment details
Prior to screening, subjects who have tested positive for a sensitizing Epidermal growth factor receptor (EGFR) mutation to determine eligibility for treatment with erlotinib. All participants underwent inclusion exclusion criteria assessment and all eligible participants signed the informed consent before undergoing any study-related procedures.
Participants by arm
| Arm | Count |
|---|---|
| Ficlatuzumab Plus Erlotinib Participants received 150 mg Erlotinib orally once daily starting on Day 1 of Cycle 1 with 20 mg/kg Ficlatuzumab administered intravenously once every 2 weeks on Day 1 and Day 15 of each 28 day cycle. | 7 |
| Placebo Plus Erlotinib Participants received 150 mg Erlotinib orally once daily starting on Day 1 of Cycle 1 with Placebo administered intravenously once every 2 weeks on Day 1 and Day 15 of each 28 day cycle. | 3 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Study terminated by the sponsor | 5 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Ficlatuzumab Plus Erlotinib | Placebo Plus Erlotinib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 3 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 1 / 3 |
| other Total, other adverse events | 7 / 7 | 3 / 3 |
| serious Total, serious adverse events | 3 / 7 | 1 / 3 |
Outcome results
Primary
Progression Free Survival (PFS)
Progression Free Survival is defined as the time from the date of randomization to the date of the first objective documentation of radiographic disease progression or death due to any cause, whichever occurs first.
Time frame: Approximately 24 months
Population: The study was terminated prior to completing enrollment; after determining that enrollment of subjects was much lower than expected, no data was collected for this outcome measure.
Secondary
Number of Participants With Adverse Events
To evaluate Safety and tolerability of ficlatuzumab plus erlotinib versus placebo plus erlotinib in subjects who have previously untreated metastatic EGFR-mutated NSCLC and a BDX004 Positive Label.
Time frame: Approximately 24 months
Population: All participants who received one dose of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ficlatuzumab Plus Erlotinib | Number of Participants With Adverse Events | Patients with Treatment-Emergent Adverse Events | 7 Participants |
| Ficlatuzumab Plus Erlotinib | Number of Participants With Adverse Events | Patients with Serious Adverse Events | 3 Participants |
| Ficlatuzumab Plus Erlotinib | Number of Participants With Adverse Events | Patients with grade 5 TEAEs | 0 Participants |
| Ficlatuzumab Plus Erlotinib | Number of Participants With Adverse Events | Patients with grade 3 or 4 TEAEs | 4 Participants |
| Ficlatuzumab Plus Erlotinib | Number of Participants With Adverse Events | Patients permanently discontinued | 2 Participants |
| Ficlatuzumab Plus Erlotinib | Number of Participants With Adverse Events | Patients with dose reduction or interruption | 3 Participants |
| Placebo Plus Erlotinib | Number of Participants With Adverse Events | Patients permanently discontinued | 0 Participants |
| Placebo Plus Erlotinib | Number of Participants With Adverse Events | Patients with Treatment-Emergent Adverse Events | 3 Participants |
| Placebo Plus Erlotinib | Number of Participants With Adverse Events | Patients with grade 3 or 4 TEAEs | 1 Participants |
| Placebo Plus Erlotinib | Number of Participants With Adverse Events | Patients with Serious Adverse Events | 1 Participants |
| Placebo Plus Erlotinib | Number of Participants With Adverse Events | Patients with dose reduction or interruption | 0 Participants |
| Placebo Plus Erlotinib | Number of Participants With Adverse Events | Patients with grade 5 TEAEs | 0 Participants |