Neoantigen Vaccine + Durvalumab for Small Cell Lung Cancer

Not currently recruiting at 1 trial location

Overseen By Jeffrey Ward, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Platinum-based chemotherapy

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Brain metastases, Autoimmune disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a personalized vaccine, combined with the drug durvalumab (Imfinzi), can slow the progression of extensive stage small cell lung cancer. The goal is to determine if this combination helps patients live longer without cancer worsening. Volunteers diagnosed with extensive stage small cell lung cancer who can receive chemotherapy with durvalumab might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 14 days before starting the trial, except for certain types of steroids. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that durvalumab, a treatment for many solid cancers, is generally safe and well-tolerated. Studies have found it can be used safely after certain cancer treatments without causing unexpected side effects. In small cell lung cancer, real-world evidence supports its use with chemotherapy, indicating it is manageable for patients.

Early studies suggest the personalized neoantigen vaccine is designed to activate the body's immune system to attack cancer cells. Initial research has shown potential benefits, but detailed safety results are still being collected. This vaccine is innovative because it is tailored to each patient's unique cancer profile.

Both durvalumab and the neoantigen vaccine have shown promising safety signs in previous research, but ongoing studies are essential to fully understand their safety profiles. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of the personalized neoantigen vaccine and durvalumab for treating small cell lung cancer because it introduces a new approach compared to traditional therapies like chemotherapy. This treatment is unique because it uses a personalized neoantigen DNA vaccine to target specific cancer markers unique to each patient's tumor, potentially boosting the immune system's ability to fight cancer more effectively. Additionally, durvalumab is an immune checkpoint inhibitor that works by blocking a protein called PD-L1, helping the immune system detect and attack cancer cells. Together, these treatments could offer a more targeted and effective way to combat small cell lung cancer, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

In this trial, participants will receive a combination of durvalumab and a personalized neoantigen vaccine. Research has shown that durvalumab, when combined with chemotherapy, may help treat small cell lung cancer (SCLC). Real-world evidence suggests this combination can be effective for SCLC patients. Studies indicate that a personalized neoantigen vaccine can enhance the immune system's ability to fight cancer. This vaccine has successfully controlled tumor growth in other cancer types. Together, these treatments might improve outcomes for patients with extensive-stage small cell lung cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

Jeffrey Ward, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults with extensive stage small cell lung cancer (ES-SCLC) suitable for platinum-based chemo and durvalumab as a first treatment. They must have good organ function, be willing to use birth control, weigh over 30 kg, and have a life expectancy of at least 12 weeks. Exclusions include those with certain medical conditions or treatments that could interfere with the trial.

Inclusion Criteria

Ability to understand and willingness to sign an IRB approved written informed consent document

I agree to use effective birth control during and up to 90 days after treatment.

My organs and bone marrow are functioning well.

Exclusion Criteria

I cannot have shots or blood taken from my veins due to medical reasons.

You have had an organ transplant from someone else.

I have been treated with a PD-1 or PD-L1 inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Patients receive durvalumab in combination with carboplatin and etoposide for 4 cycles, every 3 weeks

12 weeks

4 visits (in-person)

Consolidation Treatment

Patients receive durvalumab with the neoantigen DNA vaccine for 6 cycles, every 4 weeks

24 weeks

6 visits (in-person)

Maintenance Treatment

Patients may continue to receive durvalumab every 4 weeks until disease progression or drug toxicity

Until progression or toxicity

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Personalized Neoantigen Vaccine

Trial Overview The trial is testing if adding a personalized neoantigen vaccine to the drug durvalumab improves survival without disease progression in ES-SCLC patients. Participants will receive regular blood draws and injections using the TDS-IM v2.0 Device alongside their standard treatment.

How Is the Trial Designed?

Group I: Neoantigen DNA vaccine+durvalumab Experimental Treatment 4 Interventions

* 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.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Durvalumab, an antibody that targets PD-L1, shows antitumor activity as a consolidation therapy for patients with locally advanced unresectable non-small cell lung cancer (NSCLC).

This report presents the first known case of fully reversible bronchiolitis and bronchiectasis induced by durvalumab, challenging the previous belief that such conditions were irreversible following immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab-induced lesions of bronchiolitis and fully reversible bronchiectasis in a patient with non-small cell lung cancer: A case report. Domblides, M., Geier, M., Decroisette, C., et al.[2021]

Immune checkpoint inhibitors (ICIs), particularly durvalumab, have significantly improved treatment outcomes for patients with advanced non-small cell lung cancer (NSCLC), establishing them as the standard of care either alone or with chemotherapy.

Durvalumab is specifically approved as a consolidation treatment after chemo-radiotherapy for stage III NSCLC, highlighting its role in enhancing patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context. Gullapalli, S., Remon, J., Hendriks, LEL., et al.[2020]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

Durvalumab, an immune checkpoint inhibitor, has shown promising efficacy in treating advanced non-small cell lung cancer (NSCLC) in early phase trials, demonstrating a good safety profile.

The PACIFIC trial has successfully met its primary endpoint, indicating that durvalumab may be an important part of future treatment strategies for NSCLC, with ongoing studies potentially confirming its superiority over current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI 4736 (durvalumab) in non-small cell lung cancer. Jeanson, A., Barlesi, F.[2021]

In a study of 81 patients with unresectable locally advanced non-small cell lung cancer (NSCLC), those with high tumor mutational burden (TMB-high) showed significantly better outcomes, including lower local-regional failure rates (9% vs 51%) and improved progression-free survival (66% vs 27%) compared to TMB-low patients.

The study suggests that TMB status could be a valuable biomarker for personalizing treatment strategies, as it was the only factor significantly associated with local-regional failure and progression-free survival after treatment with chemoradiation and adjuvant durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. Lebow, ES., Shepherd, A., Eichholz, JE., et al.[2023]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(24)00556-8/fulltext

215TiP A phase II study of durvalumab (MEDI 4736) ... DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance specifically in frail LD-SCLC pts who have not progressed following concomitant or ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9760036/

Forthcoming Phase II Study of Durvalumab (MEDI4736) Plus ... This is the first prospective study to evaluate the effects of an ICI with PE specifically in ES-SCLC patients with brain metastases.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423

NCT02087423 | A Global Study to Assess the Effects of ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.8536

A phase II study of durvalumab (MEDI4736) immediately ... Durvalumab can be safely administered immediately after completion of CCRT for patients with unresectable stage III NSCLC, no additional or unexpected toxicity ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT367664

Real-world data of durvalumab plus chemotherapy for ... The aim of this study was to evaluate the efficacy of durvalumab plus chemotherapy in small cell lung cancer (SCLC) patients in real world experience.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(DURVALUMAB%20OR%20MEDI4736%20OR%20MEDI-4736%20OR%20Imfinzi))&rank=10

A Global Study to Assess the Effects of MEDI4736 ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...