The primary objective of this study is t assess whether the change in the ratio of effector T
cells (Teff) to regulatory T cells (Treg), i.e. CD8 positive/FoxP3 expressing CD4 T cells,
between pre- and on- treatment biopsies, will predict clinical response in patients with
recurrent SCLC treated with combination therapy with nivolumab and ipilimumab.
Secondary objectives of the study include: to determine the objective response rate per
RECIST 1.1 and immune-related response criteria, duration of response, progression free
survival, and overall survival with nivolumab and ipilimumab in patients with recurrent SCLC;
to evaluate changes in the tumor immune microenvironment and blood after treatment with
ipilimumab and nivolumab; and to evaluate circulating tumor DNA (ctDNA) as a marker for
response to therapy.
Inclusion:
- Patients with an active autoimmune disease requiring systemic treatment within the
past 3 months, or a syndrome that requires systemic steroids greater than
dexamethasone 2 mg daily (or equivalent) or immunosuppressive agents within the past 3
months will be ineligible. Patients with a documented history of severe autoimmune
disease but have been off of steroids and immunosuppressive agents for greater than 3
months, or only require intermittent steroid bursts may be eligible following
discussion and approval from the Principal Investigator. Subjects with vitiligo or
resolved childhood asthma/atopy would be an exception to this rule. Subjects who
require intermittent use of inhaled steroids or local steroid injections would not be
excluded from the study. Subjects with hypothyroidism stable on hormone replacement,
or psoriasis not requiring systemic therapy (within the past 3 years) or Type 1
diabetes on stable insulin will not be excluded from the study
- Histologically or cytologically documented Extensive Stage Small Cell Lung Cancer with
documented disease progression after at least one prior systemic regimen, including
one platinum-based regimen, with progression of disease on or after their most recent
therapy. Patients previously diagnosed with limited stage Small Cell Lung Cancer
treated with concurrent chemoradiation with a platinum doublet now diagnosed with
recurrent extensive disease are eligible.
- ECOG performance status of 0 to 2
- Measurable disease with at least one tumor site amenable to biopsy
- Patients may have untreated asymptomatic Central Nervous System (CNS) metastases or
treated CNS metastases if they are not currently receiving corticosteroids greater
than dexamethasone 2 mg daily or equivalent for 7 days prior to the first dose of
study drug. Patients should have completed stereotactic radiation or whole-brain
radiation at least 2 weeks prior to Cycle 1, Day 1
Exclusion:
- Patients with an active autoimmune disease requiring systemic treatment within the
past 3 months or a documented history of clinically severe autoimmune disease, or a
syndrome that requires systemic steroids > dexamethasone 2 mg daily (or equivalent
dose of other corticosteroids) or other immunosuppressive agents.
- Treatment with systemic immunosuppressive medications including but not limited to,
dexamethasone at doses > 2 mg or equivalent dose of other corticosteroids,
cyclophosphamide, tacrolimus, sirolimus, azathioprine, methotrexate, thalidomide, and
antitumor necrosis factor (anti-TNF) agents within 2 weeks prior to initiation of
trial therapy. Inhaled or topically applied steroids, and acute and chronic
standard-dose NSAIDs are permitted. Replacement steroids are also permitted.
- Prior treatment with anti-CTLA4 antibodies. Prior anti-PD1 or anti-PDL1 therapy is
allowed.
- Symptomatic untreated CNS metastases. Patients with asymptomatic CNS metastases are
eligible. Patients with symptomatic brain metastases are eligible, provided they meet
all of the following criteria:
- Completed stereotactic radiosurgery or whole- brain radiation at least 2 weeks
prior to Cycle 1, Day 1.
- No evidence of interim progression between the completion of CNS-directed therapy
and the start of trial therapy.
- No ongoing requirement for steroids greater than dexamethasone 2 mg daily (or
equivalent dose of other corticosteroids) as therapy for CNS disease;
anticonvulsants at a stable dose are allowed.
- History of leptomeningeal carcinomatosis.
- Interstitial lung disease that is symptomatic or may interfere with the detection or
management of suspected drug-related pulmonary toxicity.
- Any systemic anti-cancer chemotherapy, within 21 days prior to initiation of study
treatment.
- Treatment with any other investigational agent or participation in another clinical
trial with therapeutic intent within 21 days prior to enrollment.
- Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure, unstable angina pectoris, or psychiatric illness/social
situations that would limit compliance with study requirements.
- Major surgery or traumatic injury within 4 weeks of starting study drug.
- - Women who are pregnant or lactating.
- - Known infection with HIV, HBV or HCV. Patients with prior exposure to hepatitis, but
no evidence of active or chronic infection, may be eligible.
- - Evidence of end-organ damage as defined by the following laboratory results obtained
within 14 days prior to the first study treatment:
- ANC <1,000 cells/µL (without granulocyte colony-stimulating factor support within
2 weeks prior to Cycle 1, Day 1).
- Platelet count <75,000/µL (without transfusion within 2 weeks prior to Cycle 1,
Day 1).
- Hemoglobin <8.0 g/dL (Patients may be transfused to meet this criterion).
- AST and ALT ≥2.5 x ULN, with the following exceptions: Patients with documented
liver metastases: AST and/or ALT≥5 x ULN. o Serum bilirubin ≥1.5 x ULN (Patients
with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be
enrolled).
- INR and aPTT ≥1.5 x ULN (This applies only to patients who are not receiving
therapeutic anticoagulation; patients receiving therapeutic anticoagulation
should be on a stable dose).
