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Lung Non-Small Cell CarcinomaPhase 1NCT03546361

CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer

A Phase 1 study testing Autologous Dendritic Cell-Adenovirus CCL21 Vaccine and Pembrolizumab in people with Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of autologous dendritic cell-adenovirus CCL21 vaccine (CCL21-gene modified dendritic cell vaccine) combined with intravenous pembrolizumab, and to see how well they work in treating patients with stage IV non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Autologous Dendritic Cell-Adenovirus CCL21 Vaccine and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
8 Jul 2019to 11 Jan 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants with histologically confirmed diagnosis of NSCLC will be enrolled in this study.
  • Stage IV pathologically proven NSCLC.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  • Must have received prior systemic anti-cancer therapy for advanced disease that includes either:
  • A PD-1 and/or PD-L1 inhibitor in patients without a sensitizing EGFR mutation and/or ALK gene rearrangement or.
  • Have received prior tyrosine kinase inhibitor therapy in patients with a sensitizing EGFR mutation and/or ALK gene rearrangement. For patients with sensitizing EGFR mutations, prior therapy must include osimertinib if a T790M mutation in the EGFR gene has been documented, and for patients with ALK gene rearrangements, prior therapy must include a second generation ALK inhibitor (e.g. alectinib, brigatinib, ceritinib). Note: For this group, prior cytotoxic chemotherapy is permitted, but prior therapy with a PD-1 or PD-L1 inhibitor is not permitted.
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  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1.
  • Absolute neutrophil count (ANC) >= 1500/uL.
  • Platelets >= 100,000/uL.
  • Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L.
  • Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
  • Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30mL/min for participant with creatinine levels >1.5 x institutional ULN.
  • Creatinine clearance (CrCl) should be calculated per institutional standard.
  • Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN.
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases).
  • International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial prothrombin time (aPTT) is within therapeutic range of intended use of anticoagulants.
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
  • A lesion that either:
  • Is intended to be accessed bronchoscopically OR.
  • Is intended to be accessed with computed tomography (CT) guided transthoracic injection and in the estimation of the radiologist performing the procedure will not require transversing a bullae that significantly increases the risk of pneumothorax.
  • Male participants:
  • A male participant must agree to use a contraception of this protocol during the treatment period and for at least 4 months after the last dose of study treatment and refrain from donating sperm during this period.
  • Female participants:
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP). OR
  • A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 months after the last dose of study treatment.

Who cannot join

  • Comorbid disease or a medical or psychiatric condition that would impair the ability of the patient to receive or comply with the study protocol.
  • Any use of systemic corticosteroids within 10 days of treatment initiation.
  • Respiratory failure (defined as oxygen saturation [SaO2] < 90% on room air; partial pressure of carbon dioxide [PCO2] > 45 mmHg; or forced expiratory volume in one second [FEV1] <1.0 liter).
  • Acute viral, bacterial, or fungal infection, which requires specific therapy. Acute therapy must have been completed at least 7 days prior to study treatment.
  • Human immunodeficiency virus (HIV) infected patients (defined as HIV-1/HIV-2 antibody positive).
  • Patients with active hepatitis B or C. Active hepatitis B is defined as a known positive hepatitis B virus surface antigen (HBsAg) result. Active hepatitis C is defined by a known positive hepatitis (hep) C antibody (Ab) result and known quantitative hepatitis C virus (HCV) ribonucleic acid (RNA) results greater than the lower limits of detection of the assay.
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  • Hypersensitivity to any reagents used in the study.
  • Pregnancy or inadequate contraception.
  • Lactating females.
  • Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. In patients with brain metastases that have been treated with radiation therapy, treatment must end at least 14 days prior to starting study treatment. History of leptomeningeal disease is exclusionary regardless of prior therapy.
  • Subjects with organ allografts.
  • Previous or concurrent evidence of autoimmune disease requiring systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require inhaled steroid or local steroid injections will not be excluded from the study. Subjects with hypothyroidism who are managed by hormone replacement will not be excluded from the study.
  • Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: A Phase I Trial of Intratumoral Administration of CCL21-Gene Modified Dendritic Cell (Ad-CCL21-DC) Combined With Intravenous Pembrolizumab for Advanced NSCLC

This phase I trial studies the side effects and best dose of autologous dendritic cell-adenovirus CCL21 vaccine (CCL21-gene modified dendritic cell vaccine) combined with intravenous pembrolizumab, and to see how well they work in treating patients with stage IV non-small cell lung cancer. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving CCL21-gene modified dendritic cell vaccine with pembrolizumab may work better in treating patients with stage IV non-small cell lung cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Dose escalation: To determine the safety and maximum tolerated dose (MTD) of intratumoral injection of autologous dendritic cell-adenovirus CCL21 vaccine (CCL21 gene-modified DC [Ad-CCL21-DC]) when combined with intravenous pembrolizumab in 1) patients with advanced non-small cell lung cancer (NSCLC) without a sensitizing epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) gene rearrangement who have received prior systemic anti-cancer therapy for advanced disease that includes a PD -1 and/or PD-L1 inhibitor or 2) patients who have sensitizing EGFR mutations and/or ALK gene rearrangements and have received prior tyrosine kinase inhibitor therapy.

II. Dose expansion: To evaluate the objective response rate (ORR) in subjects treated with the dose established during dose escalation (ExD) of intratumoral injection of Ad-CCL21-DC when administered with intravenous pembrolizumab in 1) patients with advanced non-small cell lung cancer (NSCLC) without a sensitizing epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) gene rearrangement who have received prior systemic anti-cancer therapy for advanced disease that includes a PD -1 and/or PD-L1 inhibitor or 2) patients who have sensitizing EGFR mutations and/or ALK gene rearrangements and have received prior tyrosine kinase inhibitor therapy.

SECONDARY OBJECTIVES:

  1. To define the adverse event (AE) profile of intratumoral injection of Ad-CCL21-DC (determined during dose escalation) when administered with intravenous pembrolizumab in 1) patients with advanced non-small cell lung cancer (NSCLC) without a sensitizing epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) gene rearrangement who have received prior systemic anti-cancer therapy for advanced disease that includes a PD -1 and/or PD-L1 inhibitor or 2) patients who have sensitizing EGFR mutations and/or ALK gene rearrangements and have received prior tyrosine kinase inhibitor therapy.

II. To determine drug target activity by analyzing serial pre- and post-treatment biopsies and blood specimens of intratumoral injection of Ad-CCL21-DC (determined during dose escalation) when administered with intravenous pembrolizumab in 1) patients with advanced non-small cell lung cancer (NSCLC) without a sensitizing epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) gene rearrangement who have received prior systemic anti-cancer therapy for advanced disease that includes a PD -1 and/or PD-L1 inhibitor or 2) patients who have sensitizing EGFR mutations and/or ALK gene rearrangements and have received prior tyrosine kinase inhibitor therapy.

OUTLINE: This is a dose-escalation study of autologous dendritic cell-adenovirus CCL21 vaccine.

Patients receive pembrolizumab intravenously (IV) over 30 minutes followed by autologous dendritic cell-adenovirus CCL21 vaccine by computed tomography (CT)-guided or bronchoscopic intratumoral (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.

After completion of study treatment, patients are followed up at day 63 and every 3 months thereafter.

Being tested
Autologous Dendritic Cell-Adenovirus CCL21 Vaccine, Pembrolizumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Dendritic Cell-Adenovirus CCL21 VaccineBiological

    Given via CT-guided or bronchoscopic IT injection

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT03546361
Study groupRoleWhat they receive
Treatment (Ad-CCL21-DC vaccine, pembrolizumab)ExperimentalPatients 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.
Receives: Biological: Autologous Dendritic Cell-Adenovirus CCL21 Vaccine; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD)/maximum administered dose (MAD) (dose escalation)

    Measured: At 28 days

  2. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 (dose expansion)

    Demographic characteristics of patients including age, gender ethnicity, performance status, prior therapies and other baseline characteristics as collected on the case report form will be summarized by Ad-CCL21-DC dose cohort using descriptive statistics. For continuous variables, descriptive statistics (n, mean, standard deviation, standard error, median, minimum, and maximum) will be provided. For categorical variables, patient counts and percentages will be provided. Categories for missing data will be presented if necessary. The ORR will be summarized using descriptive statistics by dose level. The ORR will be analyzed using one-sample exact Binomial test for the patients treated at MTD or MAD in both the dose escalation phase and dose expansion phase. The 95% exact confidence interval (CI) will be provided.

    Measured: Up to 1 year

Secondary outcomes (2)

  1. Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0

    Measured: Up to 1 year

  2. Biomarker assessment

    Immunohistochemistry (IHC) will be conducted to assess biomarkers including PD-1, PD-L1, CD8, and CD4 (DC) expression. All immunologic parameters will be summarized using mean, standard deviation, median, percentile for continuous variables, and frequency and percentage for categorical variables. The summary statistics will be tabulated by time and dose level. Several plots, such as stem-and-leaf plot and normal probability plot, will be constructed to check the distribution of each variable. Transformation will be applied if the distribution of the variable is not normal. For the tumor tissue immune parameters measured at different time points, the post- treatment values will be compared with the pre-treatment values using either paired t-test or Wilcoxon signed-rank test. Box plots for pre-treatment and post-treatment data will be presented.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2018
  2. Study start8 Jul 2019
  3. Primary completion11 Jan 2026 (estimated)
  4. Study completion11 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03546361
Sponsor's protocol ID
17-000174
Other IDs
NCI-2018-01244, HEMONC CIRM IST Lung, K08CA245249
Status last verified
Jan 2025
First submitted
23 May 2018
Last updated
14 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Oh MS, Lisberg AE, Dumitras C, Tran LM, Salehi-Rad R, Krysan K, Lim RJ, Shabihkhani M, Romero T, Li S, Zeng W, Jing Z, Li R, Kahangi BP, Tsvetkova O, Suh RD, Abtin F, Genshaft SJ, Oh SS, Fishbein GA, Greenwald DR, Kahlon KS, Anand SR, Ashouri S, Goldman JW, Lee JM, Zhou XJ, Elashoff DA, Garon EB, Liu B, Dubinett SM. A CCL21 gene-modified dendritic cell vaccine combined with pembrolizumab in advanced non-small cell lung cancer: a phase I trial. Nat Commun. 2026 Oct 4;17(1):11321. doi: 10.1038/s41467-026-78130-7.

    PubMed 42967950

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous Dendritic Cell-Adenovirus CCL21 Vaccine and Pembrolizumab in people with Lung Non-Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD)/maximum administered dose (MAD) (dose escalation) (time frame: At 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03546361, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2025.

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