An Open-label Randomized Phase III Trial of BMS-936558 versus Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC)
- Conditions
- Squamous cell non small cell lung cancer1002747610029107
- Registration Number
- NL-OMON37458
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
1. Signed written informed consent
2. Men and women >= 18 years of age
3. Eastern Cooperative Oncology Group (ECOG) performance status of <= 1
4. Subjects with histologically or cytologically-documented squamous cell NSCLC who present
with Stage IIIB/ Stage IV disease or recurrent disease following radiation therapy or surgical resection.
5. Subjects must have experienced disease recurrence or progression during or after one prior
platinum-containing doublet chemotherapy regimen for advanced or metastatic disease
a. Subjects who received erlotinib as maintenance therapy (non-progressors with
platinum-based doublet chemotherapy) and progressed are eligible. However,
subjects who received a tyrosine kinase inhibitor after failure of a prior platinum based therapy are excluded
b. Subjects who received adjuvant or neoadjuvant platinum-doublet chemotherapy
(after surgery and/or radiation therapy) and developed recurrent or metastatic disease within 6 months of completing therapy are eligible.
c. Subjects with recurrent disease > 6 months after adjuvant or neoadjuvant platinum based
chemotherapy, who also subsequently progressed during or after a platinum doublet
regimen given to treat the recurrence, are eligible.
6. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria; Radiographic
Tumor Assessment performed within 28 days of randomization. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site
7. A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor
sample (archival or recent) must be available for biomarker evaluation. Biopsy
should be excisional, incisional or core needle. Fine needle aspiration is insufficient.
8. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests including completion of patient reported outcomes questionnaires and other requirements of the study.
9. All baseline laboratory requirements will be assessed and should be obtained within -14 days of randomization. Screening laboratory values must meet the following criteria
i) WBCs >= 2000/µL
ii) Neutrophils >= 1500/µL
iii) Platelets >= 100 x 10³/µL
iv) Hemoglobin >= 9.0 g/dL
v) Serum creatinine of <= 1.5 X ULN or creatinine clearance > 40 mL/minute
(using Cockcroft/Gault formula)
vi) AST <= 1.5X ULN
vii) ALT <= 1.5X ULN
viii) Total bilirubin <= ULN (except subjects with Gilbert Syndrome who must have total bilirubin <3.0 mg/dL)
10. Prior radiotherapy or radiosurgery must have been completed at least 2 weeks prior to randomization
11. Women of childbearing potential (WOCBP) must use method(s) of contraception based on the tables in Appendix 2 of the protocol. For a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required. The individual methods of contraception should be determined in consultation with the investigator.
WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of investigational product.
Women must not be breastfeeding during the trial;12. Men who are sexually active with WOCBP must use any contraceptive method with a failure r
1. Subjects with active CNS metastases are excluded. Subjects are eligible if CNS mets are adequately treated and subjects are neurologically returned to baseline (except for residual
signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In
addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of <= 10
mg daily prednisone (or equivalent).
2. Subjects with carcinomatous meningitis
3. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I
diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring
hormone replacement, or conditions not expected to recur in the absence of an external trigger
are permitted to enroll.
4. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg
daily prednisone equivalent) or other immunosuppressive medications within 14 days of
randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg
daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
5. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody
(including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
6. Prior treatment on the first-line study CA184104
7. Prior treatment with docetaxel
8. Subjects with a history of interstitial lung disease
9. Other active malignancy requiring concurrent intervention
10. Subjects with previous malignancies (except non-melanoma skin cancers, and the following
in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast)
are excluded unless a complete remission was achieved at least 2 years prior to study entry
AND no additional therapy is required during the study period
11. Treatment with any investigational agent within 28 days of first administration of study
treatment
12. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (NCI CTCAE version 4) or baseline before administration of study drug.
13. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment
14, Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
15. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection.
16. History of severe hypersensitivity reactions to other monoclonal antibodies.
17. History of severe hypersensitivity reaction to prior paclitaxel
18. History of allergy or intolerance (unacceptable adverse event) to study drug components or Polysorbate-80-containing infusions.
19. WOCBP who are pregnant or breastfeeding
20. Women with a positive pregnancy test at enrolment or prior to administration of study medication
21. Ongoing or planned administration of anti-cancer therapies other than those specified in this study
22. Use of corticosteroids or other immunosuppressive medications as per Exclusion Criteria 2b
23. Strong CYP3A4 inhibitors (See Section 3.4.1 of the protocol)
24. Any other serious or uncontrolled medical dis
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective in the study will be measured by the co-primary endpoints<br /><br>of Objective Response Rate (ORR) and overall survival (OS).<br /><br>The ORR is defined as the number of subjects with a best overall response (BOR)<br /><br>of complete response (CR) or partial response (PR) divided by the number of<br /><br>randomized subjects. OS is defined as the time from randomization to the date<br /><br>of death. A subject who has not<br /><br>died will be censored at last known date alive. OS will be followed<br /><br>continuously while subjects are on the study drug and every 3 months via<br /><br>in-person or phone contact after subjects discontinue the study drug.</p><br>
- Secondary Outcome Measures
Name Time Method