Dendritic Cell Vaccine + Pembrolizumab for Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: PD-1 inhibitors, PD-L1 inhibitors, Tyrosine kinase inhibitors

Must not be taking: Systemic corticosteroids, Immunosuppressive agents

Disqualifiers: Respiratory failure, Active hepatitis, HIV, others

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

Compensation: Varies

Number of Visits: 69

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for stage IV non-small cell lung cancer by combining the Autologous Dendritic Cell-Adenovirus CCL21 Vaccine with pembrolizumab. The vaccine boosts the immune system to fight cancer cells, while pembrolizumab prevents the cancer from growing and spreading. This combination may outperform current treatments for this type of lung cancer. Individuals with stage IV non-small cell lung cancer who have not found success with other treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot use systemic corticosteroids within 10 days of starting the treatment. 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 has shown that the dendritic cell-adenovirus CCL21 vaccine may help treat lung cancer. Some studies found that patients receiving this vaccine lived for about 14.6 months on average. This suggests the vaccine is generally safe, but researchers continue to investigate specific side effects.

Pembrolizumab, in contrast, has been used for a while and is known to be safe. The FDA has already approved it for treating certain lung cancers. Long-term studies have shown it helps patients with advanced lung cancer live longer. While it can cause some side effects, these are usually manageable.

This trial tests both treatments together. The goal is to determine if combining them works better without causing too many new side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for lung cancer, which often include chemotherapy and radiation, the dendritic cell vaccine combined with pembrolizumab takes a unique approach by enhancing the body's immune response. This treatment involves using autologous dendritic cells modified with an adenovirus carrying the CCL21 gene to boost the immune system's ability to target cancer cells. Researchers are excited because this method may improve the precision and effectiveness of the immune system in fighting cancer, potentially leading to better outcomes with fewer side effects. This innovative approach offers hope for a more targeted and personalized cancer treatment.

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

Previous studies showed that a vaccine using modified cells yielded promising results for treating non-small cell lung cancer, with about 46.2% of patients experiencing stable disease. In this trial, participants will receive a combination of the autologous dendritic cell-adenovirus CCL21 vaccine and pembrolizumab. This combination might help the body fight cancer more effectively. Pembrolizumab alone has succeeded, with some patients living up to five years after treatment. Using these treatments together could potentially offer even better outcomes for patients with stage IV lung cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Edward B. Garon

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage IV non-small cell lung cancer (NSCLC) who have already tried systemic anti-cancer therapy. They must be physically able to perform daily activities (ECOG status 0 or 1), have proper kidney, liver, and blood function, and not be pregnant or breastfeeding. Participants need measurable disease by RECIST v1.1 standards and agree to use contraception.

Inclusion Criteria

My kidney function is within the required range.

My blood clotting time is normal or I'm on blood thinners.

My lung cancer is at stage IV.

Exclusion Criteria

I haven't taken any corticosteroids in the last 10 days.

I am currently being treated for an acute infection.

I have active hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients receive pembrolizumab intravenously followed by intratumoral injection of Ad-CCL21-DC to determine the safety and maximum tolerated dose

6 weeks

3 visits (in-person)

Dose Expansion

Evaluate the objective response rate with the established dose of Ad-CCL21-DC and pembrolizumab

Up to 1 year

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Day 63 and every 3 months thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Dendritic Cell-Adenovirus CCL21 Vaccine
• Pembrolizumab

Trial Overview The trial tests a combination of a CCL21-gene modified dendritic cell vaccine with pembrolizumab, an antibody treatment. The vaccine aims to help the immune system attack cancer cells while pembrolizumab may stop tumor growth by blocking certain proteins.

How Is the Trial Designed?

Group I: Treatment (Ad-CCL21-DC vaccine, pembrolizumab) Experimental Treatment 2 Interventions

Patients receive pembrolizumab IV over 30 minutes followed by autologous dendritic cell-adenovirus CCL21 vaccine by CT-guided or bronchoscopic IT injection on days 0, 21, and 42. Patients then receive pembrolizumab every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

LUNGevity Foundation

Collaborator

Trials

8

Recruited

1,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Lungevity Foundation

Collaborator

Trials

3

Recruited

180+

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

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Characteristics of a CCL21 Gene-Modified Dendritic Cell ... Characteristics of a CCL21 Gene-Modified Dendritic Cell Vaccine Utilized for a Clinical Trial in Non-Small Cell Lung Cancer. Mol Cancer Ther.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03546361

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Clinical Trial: NCT03546361 This phase I trial studies the side effects and best dose of autologous dendritic cell-adenovirus CCL21 vaccine (CCL21-gene modified dendritic ...

8. mdpi.com mdpi.com/2076-393X/13/2/185

Current Development of Therapeutic Vaccines in Lung ... Clinical findings indicate that this vaccine is associated with a median overall survival (OS) of 14.6 months (95% CI 10.6–18.8) and a progression-free survival ...

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Dendritic cell-based immunotherapy in non-small cell lung ... This article review provides an update on key clinical trial results, forming the basis for future studies to characterize the role of different ...