Clinical Trials /

Personalized Neoantigen Vaccine in Combination With Durvalumab (MEDI4736) in Extensive Stage Small Cell Lung Cancer



The investigators hypothesize that a personalized neoantigen vaccine combined with durvalumab will improve the progression free survival of patients with extensive state small cell lung cancer (ES-SCLC).

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting


Phase 2

Trial Eligibility



  • Brief Title: Personalized Neoantigen Vaccine in Combination With Durvalumab (MEDI4736) in Extensive Stage Small Cell Lung Cancer
  • Official Title: Phase II Study of a Personalized Neoantigen Vaccine in Combination With Durvalumab (MEDI4736) in Extensive Stage Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 202104143
  • NCT ID: NCT04397003


  • Extensive-stage Small Cell Lung Cancer


Neoantigen DNA vaccineNeoantigen DNA vaccine+durvalumab
DurvalumabImfinziNeoantigen DNA vaccine+durvalumab


The investigators hypothesize that a personalized neoantigen vaccine combined with durvalumab will improve the progression free survival of patients with extensive state small cell lung cancer (ES-SCLC).

Trial Arms

Neoantigen DNA vaccine+durvalumabExperimentalPatients will receive durvalumab (1500mg Q3W) in combination with standard of care carboplatin and etoposide for a total of 4 cycles given every 3 weeks Beginning 4 weeks following Cycle 4 of carboplatin/etoposide/durvalumab, patients on will then receive 6 cycles of durvalumab 1500 mg with the polyepitope neoantigen DNA vaccine, both administered once every 4 weeks Patients may then receive durvalumab every 4 weeks until disease progression or drug toxicity Should a delay in vaccine preparation occur, patients will begin durvalumab and the vaccine will be added with the subsequent cycle.
  • Neoantigen DNA vaccine
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed extensive stage small cell lung cancer

          -  Considered suitable to receive a platinum-based chemotherapy regimen with durvalumab
             as 1st line treatment for ES-SCLC.

          -  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.

          -  At least one lesion must be able to be biopsied at the time of enrollment. The site
             utilized for biopsy cannot be utilized as a target lesion for efficacy measurement.

          -  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.

          -  Baseline pulse oximetry must be > 92% on room air.

          -  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

          -  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.

        Exclusion Criteria:

          -  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
                  of disease

               -  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
             interventional study.

          -  Prior randomization or treatment in a previous durvalumab 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 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 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:

               -  uncontrolled ongoing or active infection

               -  a history of myocarditis or congestive heart failure (as defined by New York
                  Heart Association Functional Classification III or IV)

               -  myocardial infarction 6 months prior to study entry

               -  uncontrolled hypertension

               -  unstable angina pectoris

               -  serious uncontrolled cardiac arrhythmia

               -  interstitial lung disease (ILD) or a history of ILD/pneumonitis requiring
                  treatment with systemic steriods

               -  serious chronic gastrointestinal conditions associated with diarrhea

               -  psychiatric illness or 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 informed consent.

          -  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.
                  intra-articular injection)

               -  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 enrollment

          -  Less than 2 acceptable potential injection sites for IM injection and electroporation
             considering the left and right medial deltoid, and anterolateral quadriceps muscles. A
             site for injection and electroporation is not acceptable if there is inadequate muscle
             mass to support at least a 19 mm /0.75 inch injection depth or a skin pinch thickness
             measurement of >50 mm as assessed using the provided caliper). Eligible injection
             sites must also have intact lymphoid drainage and be free from tattoos, hypertrophic
             skin patches, keloids or other skin conditions which could interfere with the
             administration procedure or subsequent assessment of local reactogenicity. Note: In
             order to ensure adequate muscle mass for administrations for participants with a
             weight <65 kg, potentially eligible administration sites are confined to the outer
             aspect of the upper thigh (left or right vastus lateralis muscle). The left and right
             medial deltoid are not eligible administration sites for those participants.

          -  Is an individual in whom the ability to observe possible local site reactions at >2
             eligible injection sites (left and right medial deltoid or left and right vastus
             lateralis muscles) is, in the opinion of the investigator, unacceptably obscured due
             to a physical condition.

          -  Has a metal implant or implantable device within the area of the electroporation
             injection site at >2 of the eligible injection sites.

          -  Contraindication to intramuscular injections and/or blood draws.

          -  Any chronic or active neurologic disorder, including seizures and epilepsy, excluding
             a single febrile seizure as a child.

          -  Current use of any non-removable electronic stimulation device, such as cardiac demand
             pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep
             brain stimulators.

          -  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
                  hormone replacement

               -  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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of the combination of durvalumab and a neoantigen vaccine as measured by number of participants experiencing adverse events
Time Frame:Through 90 days after completion of treatment (estimated to be 2 years and 3 months)
Safety Issue:
Description:-Safety and tolerability will be measured by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v 5.0

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:12 months
Safety Issue:
Description:PFS is defined as the duration of time from start of durvalumab to time of progression or death, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Measure:Response conversion rate
Time Frame:Through completion of treatment (estimated to be 2 years)
Safety Issue:
Description:-The response conversion rate is defined as the proportion of patients who improve in RECIST v1.1 category subsequent to vaccination.
Measure:Duration of response (DOR)
Time Frame:Through completion of treatment (estimated to be 2 years)
Safety Issue:
Description:-The duration of response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Measure:Overall survival (OS)
Time Frame:Through completion of follow-up (estimated to be 4 years)
Safety Issue:
Description:-Defined as time from start of durvalumab to death due to any causes


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

June 25, 2021