Neoantigen Vaccine + Durvalumab for Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

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

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a custom-made vaccine combined with an immune-boosting drug called durvalumab. It aims to help patients with advanced small cell lung cancer, a severe type of lung cancer that has spread widely. The vaccine targets unique markers on cancer cells, while durvalumab helps the immune system fight these cells more effectively.

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.

What data supports the effectiveness of the drug Durvalumab for treating small cell lung cancer?

Durvalumab has shown effectiveness in treating non-small cell lung cancer (NSCLC), particularly after chemoradiation, by improving disease control and survival. It is approved as a consolidation treatment in stage III NSCLC, suggesting potential benefits in similar lung cancer types. ^{1 2 3 4 5}

Is the combination of Neoantigen Vaccine and Durvalumab safe for humans?

Durvalumab, also known as Imfinzi or MEDI4736, has been shown to have a manageable safety profile in treating various cancers, including non-small cell lung cancer. Some patients have experienced immune-related side effects, such as reversible lung issues, but overall, it is considered to have acceptable tolerability. ^{1 5 6 7 8}

What makes the Neoantigen Vaccine + Durvalumab treatment unique for small cell lung cancer?

This treatment is unique because it combines a personalized neoantigen vaccine, which is tailored to the individual's specific cancer mutations, with durvalumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the body's immune response against the cancer, offering a more targeted and potentially effective approach compared to standard treatments. ^{1 2 3 4 5}

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Durvalumab (PD-L1 Inhibitor)
• Personalized Neoantigen Vaccine (Cancer 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.

Participant Groups

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 Japan for the following indications:

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+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

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

Findings from Research

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]

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, 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, 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context. [2020]

3. England pubmed.ncbi.nlm.nih.gov

MEDI 4736 (durvalumab) in non-small cell lung cancer. [2021]

4. United States 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

8. Singapore 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. [2021]