Study with investigational drug PF-06463922 in patients with a specific type of advanced lung cancer
- Conditions
- Anaplastic Lymphoma Kinase (ALK)-positive (ALK+) or ROS oncogene 1 (ROS1)-positive (ROS1+) advanced non-small cell lung cancer (NSCLC).MedDRA version: 20.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-002620-17-BE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 332
1. Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA)-approved FISH assay (Abbott Molecular Inc) or by Immunohistochemistry (IHC) (Ventana Inc), or a ROS1 rearrangement as determined by FISH or RT-PCR or Next Generation Sequencing (NGS) via a local diagnostic test (LDT). A central laboratory confirmation by a Sponsor-selected, validated test will retrospectively determine final ROS1 status. All patients (ALK positive and ROS1 positive) must have archival tissue sample available and collected prior to enrollment.
2. Disease Status Requirements
Phase 1: ALK- positive NSCLC patients must either be treatment naïve in the advanced setting or have had disease progression after at least 1 previous ALK inhibitor therapy (ies).
Phase 2: ALK -positive NSCLC patients must either be or have had:
- Treatment naïve (ie, no prior chemotherapy in the metastatic disease
setting and no prior ALK inhibitor therapy allowed) [EXP-1];
- Disease progression after crizotinib only. No prior chemotherapy is
allowed in the metastatic disease setting. [EXP-2];
- Disease progression after crizotinib and 1 or 2 prior regimens of
chemotherapy in the metastatic disease setting. [EXP-3];
- Disease progression after 1 prior ALK inhibitor therapy other than
crizotinib. Patients may have had any number of prior chemotherapy
regimens in any disease setting. [EXP-3];
- Disease progression after 2 prior ALK inhibitor therapies. Patients may
have had any number of prior chemotherapy regimens in any disease
setting. [EXP-4];
- Disease progression after 3 prior ALK inhibitor therapies. Patients may
have had any number of prior chemotherapy regimens in any disease
setting. [EXP-5];
ROS1- positive NSCLC patients may be:
- Treatment naïve (ie, no prior chemotherapy in the metastatic disease
setting and no prior ROS inhibitor therapy). [EXP-6];
- Any number of prior therapies (ie, chemotherapy and/or ROS inhibitor
therapies). [EXP-6].
3. Tumor Requirements:
Phase 1: All Patients must have at least one measurable target extracranial lesion according to RECIST v1.1. In addition patients with asymptomatic CNS metastases (including patients asymptomatic by means of stable or decreasing doses of steroids within the last 2 weeks prior to study entry) will be eligible. The brain metastases may be newly diagnosed or be present as progressive disease after surgery, whole brain radiotherapy or stereotactic radiosurgery (see Exclusion Criterion #3 for the lapsed time period required between the end of radiotherapy and study entry). Patients who have asymptomatic radiologically suspected leptomeningeal disease (LM) or carcinomatous meningitis (CM) and negative spinal fluid (CSF) are eligible to enter Phase 1.
Phase 2: All Patients must have at least one measurable target extracranial lesion according to RECIST v1.1. In addition patients with asymptomatic CNS metastases (including patients controlled with stable or decreasing steroid use within the last 2 weeks prior to study entry) will be eligible. The brain metastases may be newly diagnosed or be present as progressive disease after surgery, whole brain radiotherapy or stereotactic radiosurgery (see Exclusion Criterion #3 for the lapsed time period required between the end of radiotherapy and study entry). Patients who have leptomeningeal disease (LM) or carcinomatous m
1.Spinal cord compression is excluded unless the patient demonstrates good pain control attained through therapy and there is stabilization or recovery of neurological function for the 4 weeks prior to study entry
2.Major surgery within 4 weeks of study entry.Minor surgical procedures are not excluded but sufficient time should have passed for wound healing
3.Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry.Palliative radiation (<=10 fractions) must have been completed at least 48 hours prior to study entry.Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study entry.Whole brain radiation must have completed at least 4 weeks prior to study entry
4.Systemic anti-cancer therapy completed within a minimum of 5 half lives of study entry. Whole brain radiation must have completed at least 4
weeks prior to study entry (unless clinically meaningful tumor flare per
discretion of the investigator, in which discussion with the sponsor is warranted) .
5.Prior therapy with an antibody or drug specifically targeting T-cell
costimulation or immune checkpoint pathways, including, but not limited
to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T
lymphocyte associated antigen 4 (anti-CTLA-4) antibody.
6.Previous high-dose chemotherapy requiring stem cell rescue
7.Prior irradiation to >25% of the bone marrow
8.Active and clinically significant bacterial, fungal, or viral infection
including HBV, HCV, known HIV or AIDS-related illness
9. Clinically significant cardiovascular disease (that is, active or <3
months prior to enrollment): cerebral vascular accident/stroke,
myocardial infarction, unstable angina, congestive heart failure (New
York Heart Association Classification Class = II), second-degree or third-degree AV block (unless paced) or any AV block with PR >220 msec.
Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled
atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless
patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc >470 msec, or congenital long QT syndrome.
10.Patients with predisposing characteristics for acute pancreatitis
according to investigator judgment (see protocol for more details).
11.History of extensive,disseminated,bilateral or presence of Grade 3 or
4 interstitial fibrosis or interstitial lung disease including a history of
pneumonitis, hypersentivity pneumonitis, interstitial pneumonia,
interstitial lung disease, obliterative bronchiolitis and pulmonary
fibrosis. Patients with history of prior radiation pneumonitis are not
excluded
12.Other severe acute or chronic medical or psychiatric
condition,including recent (within the past year) or active suicidal
ideation or behavior,or laboratory abnormality that may increase the risk
associated with study participation or investigational product
administration or may interfere with the interpretation of study results
and,in the judgment of the investigator,would make the patient
inappropriate for entry into this study
13.Patients who are investigational site staff members directly involved
in the conduct of the trial and their family members,site staff members
otherwise supervised by the Investigator,or patients who are Pfizer
employees directly involved in the conduct of the trial
14.Evidence of active malignancy within the last 3 years. See protocol
for more details
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method