The investigators hypothesize that a personalized neoantigen vaccine combined with durvalumab
and tremelimumab will improve the progression free survival of patients with extensive state
small cell lung cancer (ES-SCLC) at six months following study therapy.
- Histologically or cytologically confirmed extensive stage small cell lung cancer.
- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by
chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- Disease must be able to be biopsied.
- At least 18 years of age.
- ECOG performance status ≤ 1
- Life expectancy of at least 12 weeks.
- Body weight > 30 kg.
- Adequate normal organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1000 K/cumm
- Platelet count ≥ 75,000 K/cumm
- Serum bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x IULN unless liver metastases are present, in which
case it must be ≤ 5 x IULN
- Measured creatinine clearance > 40 mL/min or calculated creatinine clearance > 40
mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for
determination of creatinine clearance
- Adequate cardiac function defined as QTcF < 470 ms on 12-lead EKG.
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
- Women < 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥ 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses > 1 year ago, had
chemotherapy-induced menopause with last menses > 1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or
- Male and female patients of reproductive potential must be willing to employ effective
birth control from screening to 90 days after the last dose of durvalumab monotherapy
or 180 days after the last dose of durvalumab + tremelimumab combination therapy.
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable). This includes
consent for tumor/normal exome sequencing and dbGaP-based data sharing.
- Prior treatment with a PD-1 or PD-L1 inhibitor (including durvalumab).
- A history of other primary malignancy except for:
- Malignancy treated with curative intent and with no know active disease ≥ 5 years
before the first dose of study drug and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
- Adequately treated carcinoma in situ without evidence of disease
- Currently receiving any other investigational agents.
- Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
- Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical
study regardless of treatment arm assignment.
- Any unresolved toxicity NCI CTCAE grade ≥ 2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
- Patients with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis
after consultation with the PI.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab or tremelimumab may be included only after consultation
with the PI.
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks of the first dose of study drug.
- Major surgical procedure (as defined by the PI) within 28 days prior to the first dose
of study drug. Note: local surgery of isolated lesions for palliative intent is
- History of allogenic organ transplantation.
- History of leptomeningeal carcinomatosis.
- Any known history of brain metastases. Patients with known brain metastases must be
excluded from this clinical trial because of their poor prognosis and because they
often develop progressive neurologic dysfunction that would confound the evaluation of
neurologic and other adverse events.
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to durvalumab, tremelimumab, or other agents used in the study.
- Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis,
hives, or respiratory difficulty.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirements, substantially increase
the risk of incurring AEs, or compromise the ability of the patient to give written
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g.
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g. CT scan
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study
drug. Note: patients, if enrolled, should not receive live vaccine whilst receiving
study drug and up to 30 days after the last dose of study drug.
- History of syncopal or vasovagal episode as determined by medical record and history
in the 12 month period prior to randomization
- Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue
for eligible injection sites (left and right medial deltoid region) exceeds 40 mm.
- Individuals in whom the ability to observe possible local reactions at the eligible
injection sites (deltoid region) is, in the opinion of the investigator, unacceptably
obscured due to a physical condition or permanent body art.
- Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region.
- Any chronic or active neurologic disorder, including seizures and epilepsy, excluding
a single febrile seizure as a child.
- Current use of any electronic stimulation device, such as cardiac demand pacemakers,
automatic implantable cardiac defibrillator, nerve stimulators, or deep brain
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g. colitis or Crohn's disease], diverticulitis [with the
exception of diverticulosis], systemic lups erythematosus, Sarcoidosis syndrome or
Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc.]. The following are exceptions to this
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.
- History of primary active immunodeficiency.
- Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
for HCV RNA.