A Study exploring the Biologic Effects and Biomarkers of Nivolumab incombination with Ipilimumab in Subjects with Non-Small Cell Lung Cancer(NSCLC)

Phase 1

Conditions: Treatment-Naive Stage IV or recurrent Non-Small Cell Lung Cancer(NSCLC)
MedDRA version: 20.0Level: LLTClassification code 10007096Term: Cancer of lungSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: 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: EUCTR2018-000462-11-IT

Lead Sponsor: BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATIO

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 250

Inclusion Criteria

1) Signed Written Informed Consent
2) Type of Participant and Target Disease Characteristics
a) Subjects with histologically confirmed Stage IV or recurrent NSCLC,
squamous or non-squamous histology, with no prior systemic anticancer
therapy (including EGFR and ALK inhibitors) given as primary therapy for
advanced or metastatic disease. Prior adjuvant or neoadjuvant
chemotherapy is permitted as long as the last administration of the prior
regimen occurred at least 6 months prior to enrollment. Prior
chemoradiation for locally advanced disease is also permitted as long as
the last administration of chemotherapy or radiotherapy (which ever was given last) occurred at least 6 months prior to enrollment.
b) Measurable disease by CT or MRI per RECIST 1.1 criteria. Tumor
assessment performed within 28 days of start of study treatment.
c) All participants must have tissue submitted during screening. This
may include either a formalin-fixed paraffin-embedded (FFPE) tissue
block or a minimum of 15 unstained tumor tissue slides.
Part 1: For cohort assignment purposes (PD-L1 status determination),
archival tissue samples = 3 months old will be allowed to determine PDL1
IHC results. Fresh pre-dose biopsy samples (5 cores: 3 in FFPE and 2
in HypoThermosol®) will still need to be submitted.
Part 2: a fresh biopsy (preferred) or archival sample (= 3 months old) is
required for enrollment, but treatment may start before test results are
received.
d) ECOG Performance Status 0 or 1.
3) Age and Reproductive Status
a) Males and Females, ages 18 years (or age of majority) and older.
b) Women of childbearing potential (WOCBP) must have a negative
serum or urine pregnancy test (minimum sensitivity 25 IU/L or
equivalent units of HCG) within 24 hours prior to the start of study
treatment.
c) Women must not be breastfeeding.
d) Women of childbearing potential must agree to follow instructions for
method(s) of contraception for the duration of treatment followed by a
period of 30 days (duration of ovulatory cycle) plus the time required for
the investigational drug to undergo five half-lives. WOCBP treated with
nivo + ipi combination should use an adequate method to avoid
pregnancy for 5 months (30 days plus the time required for nivolumab to
undergo five half-lives) after the last dose of investigational drug.
e) Males who are sexually active with WOCBP must agree to follow
instructions for method(s) of contraception for the duration of treatment
followed by a period
of 90 days (duration of sperm turnover) plus the time required for the
investigational drug to undergo five half-lives. Males treated with nivo +
ipi combination who are sexually active with WOCBP must continue
contraception for 7 months (90 days plus the time required for
nivolumab to undergo five half-lives) after the last dose of
investigational drug. In addition, male participants must be willing to
refrain from sperm donation during this time.
f) Azoospermic males are exempt from contraceptive requirements.
WOCBP who are continuously not heterosexually active are also exempt
from contraceptive requirements, and still must undergo pregnancy
testing as described in this section.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

Exclusion Criteria

1) Medical Conditions
a) Subjects with known EGFR mutations which are sensitive to available
targeted inhibitor therapy (including, but not limited to, deletions in
exon 19 and exon 21 [L858R] substitution mutations) are excluded. All
subjects with non-squamous histology must have been tested for EGFR
mutation status; use of an FDA-approved test is strongly encouraged.
Non-squamous subjects with unknown or indeterminate EGFR status are
excluded.
b) Subjects with known ALK translocations which are sensitive to
available targeted inhibitor therapy are excluded. If tested, use of an
FDA-approved test is strongly encouraged. Subjects with unknown or
indeterminate ALK status may be enrolled.
c) Subjects with untreated CNS metastases are excluded.
d) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or
squamous cell skin cancer, superficial bladder cancer, or carcinoma in
situ of the prostate, cervix, or breast.
e) Subjects with an active, known or suspected autoimmune disease.
Subjects with type I diabetes mellitus, hypothyroidism only requiring
hormone replacement, skin disorders (such as vitiligo, psoriasis, or
alopecia) not requiring systemic treatment, or conditions not expected
to recur in the absence of an external trigger are permitted to enroll.
f) Subjects with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other
immunosuppressive medications within 14 days of enrollment. Inhaled
or topical steroids, and adrenal replacement steroid doses < 10 mg daily
prednisone equivalent, are permitted in the absence of active
autoimmune disease.
g) Subjects with interstitial lung disease that is symptomatic or may
interfere with the detection or management of suspected drug-related
pulmonary toxicity.
h) Subjects with serious or uncontrolled medical disorders and any
known medical condition that, in the investigator's opinion, would
increase the risk associated with study participation or study drug
administration or interfere with the interpretation of safety results.
i) Subjects with a known history of a positive test for human
immunodeficiency virus (HIV) or known acquired immunodeficiency
syndrome (AIDS). NOTE: Testing for HIV must be performed at sites
where mandated locally.
2) Prior/Concomitant Therapy
a) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-
4 antibody, or any other antibody or drug specifically targeting T-cell costimulation
or checkpoint pathways.
b) Treatment with botanical preparations (eg herbal supplements or
traditional Chinese medicines) intended for general health support or to
treat the disease under study within 2 weeks prior to treatment.
3) Physical and Laboratory Test Findings
Screening laboratory values that meet the following criteria (using
CTCAE v4):
a) WBC < 2000/¿L
b) Neutrophils < 1500/¿L
c) Platelets < 100 x 103/¿L
d) Hemoglobin < 9.0 g/dL
e) Serum creatinine > 1.5 x ULN, unless creatinine clearance = 40
mL/min (measured or
calculated using the Cockroft-Gault formula)
Female CrCl = (140- age in years) x weight in kg x 0.85
72 x serum creatinine in mg/ dL
Male CrCl = (140- age in years) x weight in kg x 1.00
72 x serum creatinine in mg/ dL
f) AST > 3.0 x ULN
g) ALT > 3.0 x ULN
h) Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome
who must have a total bilirubin level of < 3.0x ULN).

il campo non è completo a causa del limite

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

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