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

NCT04397003 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202104143
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Extensive-stage Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of the combination of durvalumab and a neoantigen vaccine as measured by number of participants experiencing adverse events

  -Safety and tolerability will be measured by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v 5.0

  Through 90 days after completion of treatment (estimated to be 2 years and 3 months)

• Feasibility of combining durvalumab with a neoantigen vaccine as measured by the number of participants that had a vaccine produced for them

  -Feasibility is defined as the ability to produce a vaccine for 80% of patients enrolled within 24 weeks of the start of consolidation durvalumab.

  Within 24 weeks of the start of consolidation durvalumab

Secondary Outcomes (4)

• Progression-free survival (PFS)

  12 months

• Response conversion rate

  Through completion of treatment (estimated to be 2 years)

• Duration of response (DOR)

  Through completion of treatment (estimated to be 2 years)

• Overall survival (OS)

  Through completion of follow-up (estimated to be 4 years and 3 months)

Study Arms (1)

Neoantigen DNA vaccine+durvalumab

EXPERIMENTAL

* Patients 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.

Biological: Neoantigen DNA vaccine; Drug: Durvalumab; Device: TDS-IM v2.0 Device; Procedure: Peripheral blood draws

Interventions

Neoantigen DNA vaccine BIOLOGICAL

All study injections will be given intramuscularly using an integrated electroporation device (TDS-IM system, PapiVax Biotech). At each vaccination time point, patients will receive two injections of the neoantigen DNA vaccine, one injection into each deltoid or lateralis.

Neoantigen DNA vaccine+durvalumab

Durvalumab DRUG

-Supplied by AstraZeneca

Also known as: Imfinzi

Neoantigen DNA vaccine+durvalumab

TDS-IM v2.0 Device DEVICE

-Integrated electroporation administration system

Neoantigen DNA vaccine+durvalumab

Peripheral blood draws PROCEDURE

-Pre-treatment, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Vaccine Day 1, Vaccine Day 29, Vaccine Day 85, Vaccine Day 141, on even numbers of cycles for durvalumab for one year following completion of vaccine

Neoantigen DNA vaccine+durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed extensive stage small cell lung cancer (ES-SCLC)
• 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 ≥ 1.0 K/cumm
• Platelet count ≥ 75 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

You may not qualify if:

• 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.
• 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 acceptable.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• AstraZeneca: collaborator
• Gateway for Cancer Research: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jeffrey Ward, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2020
• First Posted: May 21, 2020
• Study Start: March 30, 2022
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2029
• Last Updated: October 22, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)