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Mesothelioma, MalignantPhase 1MESOVAXNCT03546426

Pembrolizumab Plus Autologous Dendritic Cell Vaccine in Patients with PD-L1 Negative Advanced Mesothelioma Who Have Failed Prior Therapies

A Phase 1 study testing Pembrolizumab, Autologous dendritic cells and Interleukin-2 in people with Mesothelioma, Malignant and PD-L1 Negative, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 1 site in Italy.

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

Pembrolizumab plus autologous dendritic cell vaccine in patients with PD-L1 negative advanced mesothelioma who have failed prior therapies.This is an exploratory, single-arm, open-label, phase 1b clinical trial. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab, Autologous dendritic cells and Interleukin-2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteItaly
Study dates
12 Dec 2019to Sep 2028
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

  • Histologically or cytologically confirmed mesothelioma, with PD-L1 expression in less than 1% of cell in the screening tumor biopsy.
  • Progressive disease after at least one treatment line for advanced disease. Previous treatments must have included an antifolate agent and a platinum compound.
  • Patients must have recovered (grade 1 or less by CTCAE 4.0) from all the adverse events related to previous treatments.
  • The autologous surgical specimen needed for vaccine manufacturing must have been collected and sent to the Somatic Cell Therapy Lab of IRST IRCCS and must fulfil all the acceptance criteria prescribed by the GMP procedures.
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be ≥ 18 years of age on day of signing informed consent.
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  • Have measurable disease based on modified RECIST 1.0 for pleural mesothelioma or RECIST 1.1 for peritoneal mesothelioma.
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (screening tumor biopsy). Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1.Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • Demonstrate adequate organ function as defined in Table 1; all screening labs should be performed within 10 days of treatment initiation.
  • Patients aged 70 years or older must have left ventricular ejection fraction not lower than 55% as assessed by echocardiography.
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential must be willing to use an adequate method of contraception . Contraception, for the course of the study through 120 days after the last dose of study medication.
  • Male subjects of childbearing potential must agree to use an adequate method of contraception - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Who cannot join

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 10 mg prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Patients who have had chemotherapy, targeted small molecule therapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events(i.e., ≤ Grade 1 or at baseline) due to agents administered more than 4 weeks earlier.
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  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Previous treatment with a cancer vaccine, or with agents targeting the PD-1/PD-L1 or PD-L2 axis.
  • Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years, except basal or squamous cell carcinoma of the skin and in situ carcinoma of the cervix uteri treated with radical surgery.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment, excepting for less than 10 mg prednisone equivalent. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of active, non-infectious pneumonitis or interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has 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.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Any known history of or positivity of any serologic marker indicative of infection by Treponema pallidum, hepatitis B virus (HBsAg, HBsAb, HBcAB), hepatitis C virus (HCVAb, HCV RNA quantitative), human immunodeficiency virus (HIV), whether actual or previous. The sole positivity for antibodies against the HBsAg Ab (i.e. with all other HBV markers negative) is indicative of previous HBV vaccination and therefore is acceptable.
  • Has received a live vaccine within 30 days of planned start of study therapy.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

    Meldola, FC, 47014

Other trials in Italy

About this study

Pembrolizumab plus autologous dendritic cell vaccine in patients with PD-L1 negative advanced mesothelioma who have failed prior therapies.This is an exploratory, single-arm, open-label, phase 1b clinical trial.

Patients will receive pembrolizumab 200 mg and autologous dendritic cell vaccine every 3 weeks for the first 6 cycles, followed by pembrolizumab 200 mg every 3 weeks until confirmed progression or for a maximum of 2 years (see Figure 1 Study Schema).

After each vaccine administration patients will receive IL-2 3 MU s.c. for 5 days, from day +2 to day +6.

Read the detailed description

Pembrolizumab plus autologous dendritic cell vaccine in patients with PD-L1 negative advanced mesothelioma who have failed prior therapies.This is an exploratory, single-arm, open-label, phase 1b clinical trial.

The study will explore treatment safety and the ability to induce PD-L1 expression of the study treatment. Secondary objective will include clinical activity and immunological efficacy.

18 Patients will be enrolled . To ensure patients' protection and avoid unacceptable toxicity, a formal safety analysis will be conducted after six patients have been observed for at least 30 days after the third treatment cycle.

The study will be conducted on PD-L1 negative advanced mesothelioma patients with progressive disease after standard therapy. Previous therapies must have included an antifolate agent and a platinum compound.

Study treatment: Pembrolizumab 200 mg IV q3w until disease progression, unacceptable toxicity or informed consent withdrawal, or for a maximum of 2 years Autologous dendritic cells loaded with autologous tumor homogenate, 107 cells ID q3w for up to six doses Interleukin-2 3 MU s.c. from day +2 to day +6 after each DC administration.

Being tested
Pembrolizumab, Autologous dendritic cells, Interleukin-2
Keywords
Mesothelioma, Malignant, PDL-1 negative, advanced disease, progressive disease
Medical subject headings
Mesothelioma, Malignant, Disease Progression

What participants receive

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

  • PembrolizumabDrug

    200 mg IV q3w until disease progression, unacceptable toxicity or informed consent withdrawal, or for a maximum of 2 years

  • Autologous dendritic cellsBiological

    Autologous dendritic cells (DC) loaded with autologous tumor homogenate, 10 x7 cells ID every 3 weeks for up to six doses

  • Interleukin-2Drug

    3 MU s.c. from day +2 to day +6 after each DC administration

Study groups in NCT03546426
Study groupRoleWhat they receive
study treatmentExperimentalPembrolizumab in combination with Autologous dendritic cells and Interleukin-2
Receives: Drug: Pembrolizumab; Biological: Autologous dendritic cells; Drug: Interleukin-2

What is being measured

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

  1. Safety as proportion of patients experiencing treatment-related adverse events

    The proportion of patients experiencing treatment-related grade 3-4 adverse events (AEs) according to NCI-CTCAE criteria, version 4.0.

    Measured: up to 90 days after end of study treatment

  2. PD-L1 expression induction by the treatment

    Proportion of patients showing PD-L1 expression ≥ 1% of cells on post-treatment tumor samples.

    Measured: up to 24 months

Secondary outcomes (2)

  1. treatment activity

    Clinical response by modified RECIST 1.0 for pleural mesothelioma and RECIST 1.1 criteria for peritoneal mesothelioma.

    Measured: up to 24 months

  2. Immunological efficacy

    Immunological activity will be evaluated by characterizing circulating immune response against universal and mesothelioma-associated tumor antigens by ELISPOT analysis and DTH skin test

    Measured: up to 24 months

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 start12 Dec 2019
  3. Primary completionJan 2027 (estimated)
  4. Study completionSep 2028 (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
Single group
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03546426
Sponsor's protocol ID
IRST100.39
Acronym
MESOVAX
Status last verified
Sep 2024
First submitted
23 May 2018
Last updated
1 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab, Autologous dendritic cells and Interleukin-2 in people with Mesothelioma, Malignant and PD-L1 Negative, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 1 site in Italy.

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 14 inclusion and 19 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 1 Oct 2024. 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 Italy. 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?

Safety as proportion of patients experiencing treatment-related adverse events (time frame: up to 90 days after end of study treatment). 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 NCT03546426.

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 1 Oct 2024.

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