Ipilimumab and Nivolumab in the Treatment of Malignant Pleural Mesothelioma

NCT03048474 | Completed Phase 2 DMC

• 1 other identifier: N16INM
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, monocenter, single arm, phase II trial in 33 patients with unresectable MPM, who experience disease progression or recurrence after at least one previous line of platinum-based systemic treatment. Nivolumab will be administered at a fixed dose of 240 mg every 2 week. Nivolumab will be given in combination with ipilimumab on week 1, 7, 13 and 19 and will be administered prior to the infusion of ipilimumab. Ipilimumab will be administered at the dose of 1 mg/Kg.The patients will receive nivolumab monotherapy on week 3, 5, 9, 11, 15 and 17. From week 21 thereafter, Nivolumab will be then administered every 2 weeks for a maximum period of 2 years or until disease progression or unacceptable toxicity occurs.

Conditions

Malignant Pleural Mesothelioma

Keywords

progressive disease after at least 1 course of chemotherapy

Outcome Measures

Primary Outcomes (1)

• Disease Controle Rate (DCR) at 12 weeks

  The number of patients that have CR or PR plus the number of patients with stable disease as a percentage of the total number of patients in the study.

  at 12 weeks

Secondary Outcomes (5)

• Safety: the incidence of adverse events, serious adverse events, deaths and laboratory abnormalities.

  Participants will be followed for the duration of the trial, an expected average of 6 weeks

• Disease Controle Rate (DCR) at 6 months

  at 6 months

• Progression Free Survival (PFS)

  Until progression, every 6 weeks up to 48 weeks

• Overall Survival (OS)

  every 6 weeks up to 48 weeks, thereafter every 12 weeks up to 36 months.

• Overall Response Rate (ORR)

  Every 6 weeks up to 48 weeks

Other Outcomes (1)

• Exploratory in blood and tumor biopsies

  At screening and after 6 weeks of treatment (day 56-70)

Study Arms (1)

Nivolumab and Ipilimumab

EXPERIMENTAL

Nivolumab will be administered at a fixed dose of 240 mg every 2 weeks for a maximum period of 2 years. Nivolumab will be given in combination with ipilimumab on week 1, 7, 13 and 19. Ipilimumab will be administered at the dose of 1 mg/Kg.

Drug: nivolumab and ipilimumab

Interventions

nivolumab and ipilimumab DRUG

Also known as: BMS-936558 and L01XC11

Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form
• Age ≥ 18 years
• WHO-ECOG performance status 0 or 1
• Able to comply with the study protocol, in the investigator's judgment
• Progressive disease after at least one prior systemic treatment with a platinum-based doublet (both cisplatin and carboplatin are allowed) for unresectable MPM. All prior cytotoxic toxicities must have resolved to grade ≤ 1 prior to registration
• Measurable disease on CT scan, according to modified RECIST Criteria for Mesothelioma (Byrne MJ, 2004)
• Life expectancy ≥ 12 weeks
• Adequate hematologic and organ function, defined by the following laboratory results, obtained within 14 days prior to the first study treatment:
• Absolute neutrophil count (ANC) ≥ 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
• WBC count ≥ 3000 cells/µL
• Lymphocyte count ≥ 250 cells/µL
• Platelet count ≥ 100.000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
• Hemoglobin ≥ 5.6 mmol/L
• Serum albumin ≥ 25 gr/L
• AST, ALT and alkaline phosphatase ≤ 2.5 x ULN, with the following exceptions: patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN

You may not qualify if:

• Medical or psychological impediment to comply with the protocol
• Patients with only peritoneal MPM
• Prior malignancy except adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the patient has been disease-free for at least five years
• Concomitant participation in another clinical trial (by the investigator's judgment)
• Uncontrolled pleural/peritoneal effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrolment.
• Previous treatment with any checkpoint inhibitor
• Pregnant or lactating women
• Patients with brain metastases
• History of or active autoimmune disease (e.g. pneumonitis; rheumatoid arthritis; severe form of psoriasis; uncontrolled type I diabetes or hypothyroidism)
• History of idiopathic pulmonary fibrosis (including pneumonitis) or unresolved drug-induced pneumonitis, organizing pneumonia, or active pneumonitis on screening chest CT scan
• History of relevant gastrointestinal disease, including, but not limited to, Crohn's disease, ulcerative colitis, recurrent diverticulitis
• Prior allogenic bone marrow transplantation or prior solid organ transplantation
• History of HIV
• Patients with history of HBV infection are eligible if serological profile is compatible with past/resolved infection (defined as negative HBsAg test and positive antibody to HBV core antigen \[anti-HBc\] antibody test) and HBsAg test and HBV-DNA are both negative prior to Cycle 1, Day 1

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Netherlands Cancer Institute-Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, North Holland, 1066CX, Netherlands

Location

Related Publications (3)

• Desai AP, Kosari F, Disselhorst M, Yin J, Agahi A, Peikert T, Udell J, Johnson SH, Smadbeck J, Murphy S, Karagouga G, McCune A, Schaefer-Klein J, Borad MJ, Cheville J, Vasmatzis G, Baas P, Mansfield A. Dynamics and survival associations of T cell receptor clusters in patients with pleural mesothelioma treated with immunotherapy. J Immunother Cancer. 2023 Jun;11(6):e006035. doi: 10.1136/jitc-2022-006035.

  PMID: 37279993 DERIVED

• Mankor JM, Disselhorst MJ, Poncin M, Baas P, Aerts JGJV, Vroman H. Efficacy of nivolumab and ipilimumab in patients with malignant pleural mesothelioma is related to a subtype of effector memory cytotoxic T cells: Translational evidence from two clinical trials. EBioMedicine. 2020 Dec;62:103040. doi: 10.1016/j.ebiom.2020.103040. Epub 2020 Nov 7.

  PMID: 33166791 DERIVED

• Disselhorst MJ, Quispel-Janssen J, Lalezari F, Monkhorst K, de Vries JF, van der Noort V, Harms E, Burgers S, Baas P. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med. 2019 Mar;7(3):260-270. doi: 10.1016/S2213-2600(18)30420-X. Epub 2019 Jan 16.

  PMID: 30660511 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paul Baas, MD, PhD

  The Netherlands Cancer Institute-Antoni van Leeuwenhoek Ziekenhuis

  PRINCIPAL INVESTIGATOR

• Maria Disselhorst, MD

  The Netherlands Cancer Institute-Antoni van Leeuwenhoek Ziekenhuis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2016
• First Posted: February 9, 2017
• Study Start: September 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2019
• Last Updated: January 20, 2021

Record last verified: 2021-01

Locations

NL (1)