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 bbjectives 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.
- Histologically or cytologically documented ES-SCLC with documented disease progression
after at least one prior systemic regimen, including one platinum-based regimen.
- Patients previously diagnosed with limited stage SCLC treated with concurrent
chemoradiation with a platinum doublet now diagnosed with recurrent extensive disease
- ECOG performance status of 0 to 2
- Measurable disease with at least one tumor site amenable to biopsy
- Patients may have untreated asymptomatic 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.
- 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-PD1, anti-PDL1 or anti-CTLA4 antibodies.
- 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 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,
- 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.
- 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).