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Pleural MesotheliomaPhase 2NCT02588131

A Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Antibody in Malignant Mesothelioma (NIBIT-MESO-1)

A Phase 2 study testing tremelimumab plus MEDI4736 in people with Pleural Mesothelioma and Peritoneal Mesothelioma, run by Italian Network for Tumor Biotherapy Foundation at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This phase 2, open-label, single arm study aims to evaluate the efficacy of tremelimumab in combination with the anti-PD-L1 MEDI4736 in patients with unresectable malignant mesothelioma subjects Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pleural Mesothelioma, Peritoneal Mesothelioma
What is being tested?
tremelimumab plus MEDI4736
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteItaly
Study dates
Oct 2015to Mar 2018
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Willing and able to give written informed consent.
  • Histologic diagnosis of malignant mesothelioma.
  • Subjects who have refused a first line platinum-based chemotherapy, or subjects in progression of disease after a maximum of one line of platinum-based therapy for advanced disease.
  • Disease not amenable to curative surgery.
  • Measurable disease, per modified Response Evaluation Criteria in Solid Tumor [RECIST] for pleural mesothelioma or RECIST version 1.1 for peritoneal mesothelioma).
  • Life expectancy ≥ 12 weeks.
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  • ECOG performance status of 0 or 1
  • Normal laboratory tests
  • Negative screening tests for HIV, Hepatitis B, and Hepatitis C.
  • Availability of archival tumor tissue or feasibility to perform a new tumor biopsy at screening phase.
  • Men and women, of and over 18 years old. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 180 days after the last dose of investigational drug.

Who cannot join

  • Involvement in the planning and/or conduct of the study.
  • Participation in another clinical study with an investigational product during the last 6 weeks.
  • Any previous treatment with a CTLA4, PD-1 or PD-L1 inhibitor, including tremelimumab or MEDI4736.
  • History of another primary malignancy except for: malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ.
  • Receipt of the last dose of anti-cancer therapy ≤ 6 weeks prior to the first dose of study drug.
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms using Bazett's Correction.
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  • Current or prior use of immunosuppressive medication within 28 days before the first dose of tremelimumab and MEDI4736, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
  • Any unresolved toxicity (CTCAE grade >2) from previous anti-cancer therapy.
  • Any prior Grade >3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1. Active or prior documented autoimmune or inflammatory disorders
  • History of primary immunodeficiency or allogeneic organ transplant.
  • History of hypersensitivity to tremelimumab or MEDI4736 or any excipient.
  • Uncontrolled intercurrent illness including, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses
  • Known history of previous clinical diagnosis of tuberculosis.
  • History of leptomeningeal carcinomatosis.
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving tremelimumab and MEDI4736.
  • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
  • Subjects with uncontrolled seizures.

Trial locations and contacts

1 site in 1 country.

Luana Calabro', MD, PhD contact

+39-0577586116

l.calabro@ao-siena.toscana.it

Michele Maio, MD, PhD contact

+39-0577586335

mmaiocro@gmail.com

Italy1 site, 1 recruiting
  • Medical Oncology and Immunotherapy Division, University Hospital of Siena

    Siena, 53100

    Luana Calabro', MD, PhD, +39-0577586116, l.calabro@ao-siena.toscana.it

    Michele Maio, MD, PhD, +39- 0577586335, mmaiocro@gmail.com

    Recruiting

Other trials in Italy

About this study

Official title: A Single Arm, Phase II Clinical Study of Tremelimumab Combined With the Anti-PD-L1 MEDI4736 Monoclonal Antibody in Unresectable Malignant Mesothelioma Subjects: The NIBIT-MESO-1

This phase 2, open-label, single arm study aims to evaluate the efficacy of tremelimumab in combination with the anti-PD-L1 MEDI4736 in patients with unresectable malignant mesothelioma subjects

Read the detailed description

The prognosis of malignant mesothelioma (MM) patients remains dismal and effective treatment represents a high un-met medical need. Investigators have recently reported promising clinical activity of the anti-CTLA-4 mAb tremelimumab in pre-treated MM patients: disease control rate (DCR) was 31%, and survival rate at 1- and 2-years were 48.3% and 36.7%, respectively. These initial findings were corroborated by a second study in which, based on retrospective pharmacokinetic analyses, an intensified schedule of tremelimumab was utilized. Fifty-two % of patients achieved a DCR (median duration 10.9 months). These intriguing clinical results and the emerging efficacy of immunomodulatory mAb targeting the PD-1/PD-L1 axis in different tumor types, prompted us to design the NIBIT-MESO-1 study aimed to investigate the efficacy of tremelimumab combined with the anti-PD-L1 MEDI4736 in MM patients.

Being tested
tremelimumab plus MEDI4736
Keywords
tremelimumab, anti-PD-L1 MEDI4736 (Durvalumab), malignant mesothelioma
Medical subject headings
Mesothelioma, Malignant

What participants receive

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

  • tremelimumab plus MEDI4736Drug

    Also called MEDI4736 (durvalumab)

    tremelimumab1 mg/kg i.v over 60 minutes plus MEDI 4736 20 mg/kg i.v every four weeks for 4 doses, then MEDI4736 20 mg/kg IV every four weeks for additional 9 doses.

Study groups in NCT02588131
Study groupRoleWhat they receive
tremelimumab plus MEDI4736ExperimentalTremelimumab in combination with MEDI4736
Receives: Drug: tremelimumab plus MEDI4736

What is being measured

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

  1. immune-related (ir)- objective response rate (ORR)

    proportion of subjects with complete response [CR] or partial Response [PR]) according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively.

    Measured: 60 weeks

Secondary outcomes (10)
  1. Immune-related-Disease control rate (ir-DCR)

    proportion of subjects with ir-CR, ir-PR, ir-stable disease according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively

    Measured: 60 weeks

  2. Disease control rate (DCR)

    proportion of subjects with CR, PR, stable disease according to the modified-RECIST or RECIST 1.1 in pleural or peritoneal subjects, respectively

    Measured: 60 weeks

  3. Immune-related-progression-free-survival (PFS)

    ir-PFS per ir-modified-RECIST or ir-RECIST-1.1 for pleural or peritoneal mesothelioma respectively, will be defined as the time between the date of randomization and the date of progression or death

    Measured: 60 weeks

  4. progression-free-survival (PFS)

    PFS per modified-RECIST or RECIST-1.1 for pleural or peritoneal mesothelioma respectively, will be defined as the time between the date of randomization and the date of progression or death

    Measured: 60 weeks

  5. Overall survival (OS)

    Overall Survival (OS) is defined as the time from randomization until the date of death. For those subjects who have not died, OS will be censored at the recorded last date of subject contact, and for subjects with a missing recorded last date of contact, OS will be censored at the last date the subject was known to be alive.

    Measured: 120 weeks

  6. Safety (adverse events)

    The safety endpoints include adverse events (AEs) and serious adverse events (SAEs). Reporting of safety, extent of exposure, concomitant medications and discontinuation of study therapy will be based on all subjects who received at least 1 dose of treatment. Toxicity will be registered according to the NCICTC v 4.0

    Measured: 120 weeks

  7. Immune-related-ORR based on PD-L1 tumor expression

    proportion of subjects with PD-L1 positive or negative tumor expression who achieved a complete response [CR] or partial Response [PR]) according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively.

    Measured: 60 weeks

  8. Immune-related-Disease control rate based on PD-L1 tumor expression

    proportion of subjects with PD-L1 positive or negative tumor expression who achieved a CR, PR, stable disease according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively

    Measured: 60 weeks

  9. Immune-related-progression- free-survival based on PD-L1 tumor expression

    ir-PFS per ir-modified-RECIST or ir-RECIST-1.1 for pleural or peritoneal mesothelioma respectively, will be defined in subjects with PD-L1 positive or negative tumor expression as the time between the date of randomization and the date of progression or death

    Measured: 60 weeks

  10. Overall survival based on PD-L1 tumor expression

    Overall Survival (OS) is defined in subjects with PD-L1 positive or negative tumor expression as the time from randomization until the date of death. For those subjects who have not died, OS will be censored at the recorded last date of subject contact, and for subjects with a missing recorded last date of contact, OS will be censored at the last date the subject was known to be alive.

    Measured: 120 weeks

Timeline

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

  1. First posted27 Oct 2015 (estimated)
  2. Study startOct 2015
  3. Primary completionJun 2016 (estimated)
  4. Study completionMar 2018 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02588131
Sponsor's protocol ID
NIBIT-MESO-1
Status last verified
Oct 2015
First submitted
26 Oct 2015
Last updated
27 Oct 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Calabro L, Morra A, Fonsatti E, Cutaia O, Amato G, Giannarelli D, Di Giacomo AM, Danielli R, Altomonte M, Mutti L, Maio M. Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2013 Oct;14(11):1104-1111. doi: 10.1016/S1470-2045(13)70381-4. Epub 2013 Sep 11.

    PubMed 24035405
  • Calabro L, Ceresoli GL, di Pietro A, Cutaia O, Morra A, Ibrahim R, Maio M. CTLA4 blockade in mesothelioma: finally a competing strategy over cytotoxic/target therapy? Cancer Immunol Immunother. 2015 Jan;64(1):105-12. doi: 10.1007/s00262-014-1609-9. Epub 2014 Sep 19.

    PubMed 25233793
  • Calabro L, Morra A, Fonsatti E, Cutaia O, Fazio C, Annesi D, Lenoci M, Amato G, Danielli R, Altomonte M, Giannarelli D, Di Giacomo AM, Maio M. Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study. Lancet Respir Med. 2015 Apr;3(4):301-9. doi: 10.1016/S2213-2600(15)00092-2. Epub 2015 Mar 26.

    PubMed 25819643
  • Antonia et al. A Phase Ib study of MEDI4736, a programmed cell death ligand-1 (PD-L1) antibody, in combination with tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, in patients with advanced non-small cell lung cancer (NSCLC). ASCO 2015 (Abstract #3014).

  • Calabro L, Rossi G, Morra A, Rosati C, Cutaia O, Daffina MG, Altomonte M, Di Giacomo AM, Casula M, Fazio C, Palmieri G, Giannarelli D, Covre A, Maio M. Tremelimumab plus durvalumab retreatment and 4-year outcomes in patients with mesothelioma: a follow-up of the open label, non-randomised, phase 2 NIBIT-MESO-1 study. Lancet Respir Med. 2021 Sep;9(9):969-976. doi: 10.1016/S2213-2600(21)00043-6. Epub 2021 Apr 9.

    PubMed 33844995
  • Calabro L, Morra A, Giannarelli D, Amato G, D'Incecco A, Covre A, Lewis A, Rebelatto MC, Danielli R, Altomonte M, Di Giacomo AM, Maio M. Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study. Lancet Respir Med. 2018 Jun;6(6):451-460. doi: 10.1016/S2213-2600(18)30151-6. Epub 2018 May 15.

    PubMed 29773326

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing tremelimumab plus MEDI4736 in people with Pleural Mesothelioma and Peritoneal Mesothelioma, run by Italian Network for Tumor Biotherapy Foundation 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 11 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 27 Oct 2015. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Luana Calabro', MD, PhD (+39-0577586116, l.calabro@ao-siena.toscana.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

immune-related (ir)- objective response rate (ORR) (time frame: 60 weeks). 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 NCT02588131, which also lists 6 linked publications.

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 27 Oct 2015.

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