ivolumab and ipilimumab in combination for advanced malignancies.

Phase 1

Conditions: on-Small cell Lung Cancer
MedDRA version: 20.0Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-002621-10-HU

Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 500

Inclusion Criteria

1) Signed Written Informed Consent
2) Type of Participant/Target Disease Characteristics
a) Eastern Cooperative Oncology Group Performance Status of less or equal to 1.
b) Cohort A (1st-line NSCLC):
i) Participants 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.
(1)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.
(2)Prior definitive 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.
c) Cohort B (second-line NSCLC)
i) Subjects with histologically- or cytologically-documented squamous or non-squamous cell NSCLC who present with Stage IIIB/ Stage IV disease (per IASLC), or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiation therapy for locally advanced disease).
ii) Subjects must have experienced disease recurrence or progression during or after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease.
(1).Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy
(2).Subjects who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible.
(3).Subjects with recurrent disease > 6 months after platinumcontaining adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a platinum doublet-based regimen given to treat the recurrence, are eligible.
d) Evaluable disease by computed tomography (CT) or magnetic resonance imaging (MRI); radiographic tumor assessment performed within 28 days of start of study treatment.
e) Participants must have tissue submitted for PD-L1 immunohistochemical (IHC) testing prior to the treatment assignment. If PD-L1 IHC testing has already been conducted during screening for another BMS study, it does not need to be repeated for CA209817.
i) Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections, with an associated pathology report, must be submitted for biomarker evaluation prior to treatment assignment. The tumor tissue sample may be fresh or archival if obtained within 12 months prior to enrollment (6 months for slides).
ii) Tissue must be a core needle biopsy, excisional or incisional biopsy. Fine needle biopsies or drainage of pleural effusions with cytospins are not considered adequate for biomarker review. Biopsies of bone lesions that do not have a soft tissue component or decalcified bone tumor samples are also not acceptable.
(1).Samples collected via other procedures, including, but not limited to, endobronchial ultrasound (EBUS) guided biopsy, transbronchial lung biopsy (TBLB) may be approved by the BMS medical monitor (MM)/study director (SD) on a case by case basis.
f) Prior palliative radiotherapy to non-central nervous system (CNS) lesions must have been completed at least 2 we

Exclusion Criteria

1) Target Disease Exceptions
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.
Subjects with non-squamous histology and 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.
2) Medical Conditions
a) Participants with untreated CNS metastases are excluded.
i) Participants are eligible if CNS metastases are adequately treated and
participants are neurologically returned to baseline (except for residual
signs or symptoms related to the CNS treatment) for at least 2 weeks
prior to treatment assignment. In addition, participants must be either
off corticosteroids, or on a stable or decreasing dose of less or equal to
10 mg daily prednisone (or equivalent) for at least 2 weeks prior to
treatment assignment.
b) Participants with carcinomatous meningitis.
c) Participants must have recovered from the effects of major surgery or
significant traumatic
injury at least 14 days before treatment assignment.
d) Active malignancy requiring concurrent intervention.
e) Participants with an active, known or suspected autoimmune disease.
Participants 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) Participants with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other
immunosuppressive medications within 14 days of treatment
assignment. Inhaled or topical steroids, and adrenal replacement steroid
> 10 mg daily prednisone equivalent, are permitted in the absence of
active
autoimmune disease.
g) Participants with interstitial lung disease that is symptomatic or may
interfere with the detection or management of suspected drug-related
pulmonary toxicity.
h) Known history of testing positive for human immunodeficiency virus
(HIV) or known acquired immunodeficiency syndrome (AIDS).
i) 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.
3) Prior/Concomitant Therapy
a) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-
CD137, or anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell co-stimulation or checkpoint pathways
4) Physical and Laboratory Test Findings
a) White blood cells (WBC) < 2000/µL
b) Neutrophils < 1500/µL
c) Platelets < 100*103/µL
d) Hemoglobin < 9.0 g/dL
e) Serum creatinine more than 1.5 x upper limit of normal (ULN) or
calculated creatinine clearance < 40 mL/min (using the Cockcroft-Gault
formula)
f) aspartate aminotransferase (AST)/ alanine aminotransferase (ALT): >
3.0 x ULN
g) Total bilirubin more than 1.5 x ULN (except participants with Gilbert
Syndrome who must have a
tota