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

NCT ID: NCT02588131

Last Updated: 2015-10-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2018-03-31

Brief 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

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.

Conditions

Pleural Mesothelioma; Peritoneal Mesothelioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

tremelimumab plus MEDI4736

Tremelimumab in combination with MEDI4736

Group Type: EXPERIMENTAL

tremelimumab plus MEDI4736

Intervention Type: DRUG

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.

Interventions

tremelimumab plus MEDI4736

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.

Intervention Type: DRUG

Other Intervention Names

MEDI4736 (durvalumab)

Eligibility Criteria

Inclusion Criteria

• 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.
• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Italian Network for Tumor Biotherapy Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luana Calabro', MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical Oncology and Immunotherapy Division, Univeristy Hospital os Siena, Siena, Italy

Locations

Medical Oncology and Immunotherapy Division, University Hospital of Siena

Siena, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Luana Calabro', MD, PhD

Role: CONTACT

l.calabro@ao-siena.toscana.it

+39-0577586116

Michele Maio, MD, PhD

Role: CONTACT

mmaiocro@gmail.com

+39-0577586335

Facility Contacts

Luana Calabro', MD, PhD

Role: primary

l.calabro@ao-siena.toscana.it

+39-0577586116

Michele Maio, MD, PhD

Role: backup

mmaiocro@gmail.com

+39- 0577586335

References

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.

Reference Type: BACKGROUND

PMID: 24035405 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25233793 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25819643 (View on PubMed)

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).

Reference Type: BACKGROUND

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.

Reference Type: DERIVED

PMID: 33844995 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29773326 (View on PubMed)

Related Links

http://www.fondazionenibit.org/

Fondazione NIBIT

Other Identifiers

NIBIT-MESO-1

Identifier Type: -

Identifier Source: org_study_id