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

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special vaccine made from the patient's own cells and a virus, combined with a drug that boosts the immune system, in patients with advanced lung cancer who have already tried other treatments. The vaccine helps the immune system recognize cancer, and the drug helps the immune system attack it.

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 the combination of Dendritic Cell Vaccine and Pembrolizumab safe for humans?

Pembrolizumab (also known as Keytruda or MK-3475) has been studied in various cancers and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and immune-related issues such as inflammation of the lungs, liver, or thyroid. In nonhuman primate studies, pembrolizumab showed no significant toxic effects, supporting its safety profile in humans. ^{1 2 3 4 5}

What makes the dendritic cell vaccine and pembrolizumab treatment unique for lung cancer?

This treatment combines a dendritic cell vaccine, which helps the immune system recognize and attack cancer cells, with pembrolizumab, a drug that blocks a protein called PD-1 to boost the immune response against cancer. This combination aims to enhance the body's ability to fight lung cancer more effectively than using pembrolizumab alone. ^{1 2 3 6 7}

What data supports the effectiveness of the drug pembrolizumab for lung cancer?

Pembrolizumab has been approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) with high PD-L1 expression, showing significant improvements in survival compared to chemotherapy in clinical trials. ^{1 2 6 7 8}

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]

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]

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]

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]

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]

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]

Citations

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

6. United States 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. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1. [2022]