MEDI4736 Or MEDI4736 + Tremelimumab In Surgically Resectable Malignant Pleural Mesothelioma

NCT02592551 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: H-36952
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to determine whether MEDI4736 or combination therapy with MEDI4736 + tremelimumab are associated with favorable alterations of the intratumoral immunologic environment in subjects undergoing resectional surgery for Malignant Pleural Mesothelioma MPM.

Conditions

Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Change in Ratio of Intratumoral Cytotoxic T Cells to Regulatory T Cells (CD8/Treg)

  Tissue biomarker immune response of CD8 and Treg to before and after MEDI-4736 and Tremelimumab will be obtained using CytoF (time-of-flight mass cytometry) and/or flow cytometry. The ratios of CD8/Treg are calculated by diving CD8 by Treg.

  at day 1 after screening and at a surgery within one to six weeks after treatment

Secondary Outcomes (10)

• Change in Percentage of Inducible T-cell Co-stimulator (ICOS) + CD4 T Cells.

  at day 1 after screening and at a surgery within one to six weeks after treatment

• Change in Tumor Expression Programmed Death-ligand 1 (PD-L1).

  at day 1 after screening and at a surgery within one to six weeks after treatment

• Ratio of Intratumoral Cytotoxic T Cells to Regulatory T Cells (CD8/Treg) in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and in Patients Treated With MEDI-4736 Alone.

  at a surgery within one to six weeks after treatment

• Ratio of Intratumoral Cytotoxic T Cells to Regulatory T Cells (CD8/Treg) in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and Untreated Patients.

  the untreated group(control) : at day 1, MEDI4736 + Tremelimumab: at a surgery within one to six weeks after treatment (MEDI4736+Tremelimumab) group

• Percentage of Inducible T-cell Co-stimulator (ICOS) + CD4 T Cells in Patients Treated With Combination Therapy (MEDI-4736 and Tremelimumab) and in Patients Treated With MEDI-4736 Alone

  at a surgery within one to six weeks after treatment

Study Arms (3)

MEDI4736

EXPERIMENTAL

8 patients will receive an infusion of MEDI4736 (15 mg/kg intravenously, once), one to six weeks prior to surgical resection.

Drug: MEDI4736

MEDI4736 + Tremelimumab

ACTIVE COMPARATOR

8 patients will receive an infusion of MEDI4736 (1500 mg intravenously, once) + tremelimumab (75mg intravenously, once), one to six weeks prior to surgical resection.

Drug: MEDI4736; Drug: Tremelimumab

Untreated arm (control)

PLACEBO COMPARATOR

4 patients will not receive MEDI4736 or Tremelimumab.

Other: no other name

Interventions

MEDI4736 DRUG

MEDI4736 is formulated at 50 mg/mL in 26 mM histidine/histidine-HCl, 275 mM trehalose dihydrate, 0.02% (w/v) polysorbate 80, pH 6.0.

Also known as: durvalumab

MEDI4736; MEDI4736 + Tremelimumab

Tremelimumab DRUG

Tremelimumab Drug Product is formulated at a nominal concentration of 20 mg/mL in 20 mM histidine/histidine hydrochloride, 222 mM trehalose dihydrate, 0.02% (weight/volume \[w/v\]) polysorbate 80, 0.27 mM disodium edetate dihydrate (EDTA), pH 5.5.

Also known as: no other name

MEDI4736 + Tremelimumab

no other name OTHER

Neither MEDI4736 nor Tremelimumab will be used.

Untreated arm (control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age \>/= 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (\> 1500 per mm3) Platelet count ≥ 100 × 109/L (\>100,000 per mm3) Serum bilirubin ≤ 1.5× institutional upper limit of normal (ULN)AST\<3.0 Creatinine clearance \>50mL/miN Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN if documented liver metastasis are present); Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation;
• Males:
• Creatinine CL (mL/min) = Weight (kg) × (140 - Age) 72 × serum creatinine (mg/dL)
• Females:
• Creatinine CL (mL/min) = Weight (kg) × (140 - Age) × 0.85 72 × serum creatinine (mg/dL)
• Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for \>/=1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Surgically resectable MPM with no disease extension beyond the ipsilateral hemithorax
• Planned resectional surgery for MPM \[extrapleural pneumonectomy (EPP) or pleurectomy and decortication (P/D)\]
• Any MPM histology (epithelial, mixed, sarcomatoid)
• N0 or N1 nodal disease as present on perioperative chest CT and/or PET CT.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrollment or randomization in the present study
• Participation in another clinical study with an investigational product during the last 3 months
• Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 30 days prior to the first dose of study drug, and 30 days prior to the first dose of study drug for subjects who have received prior TKIs \[e.g., erlotinib, gefitinib and crizotinib\] and within 6 weeks for nitrosourea or mitomycin C).
• Current or prior use of immunosuppressive medication within 28 days before the infusion with MEDI4736 or MEDI4736 + tremelimumab and through 90 days post infusion, 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 disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of primary immunodeficiency
• History of allogeneic organ transplant
• History of hypersensitivity to MEDI4736 or any excipient
• History of hypersensitivity to tremelimumab or the combination of MEDI4736 + tremelimumab
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• Known history of previous clinical diagnosis of tuberculosis

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor St Lukes

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Lee HS, Jang HJ, Ramineni M, Wang DY, Ramos D, Choi JM, Splawn T, Espinoza M, Almarez M, Hosey L, Jo E, Hilsenbeck S, Amos CI, Ripley RT, Burt BM. A Phase II Window of Opportunity Study of Neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 Blockade for Patients with Malignant Pleural Mesothelioma. Clin Cancer Res. 2023 Feb 1;29(3):548-559. doi: 10.1158/1078-0432.CCR-22-2566.

  PMID: 36469573 DERIVED

MeSH Terms

Conditions

Mesothelioma

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Results Point of Contact

• Title: Bryan Burt, MD
• Organization: Baylor College of Medicine

burt@bcm.edu

713-798-6376

Study Officials

• Bryan Burt, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 19, 2015
• First Posted: October 30, 2015
• Study Start: May 11, 2016
• Primary Completion: August 6, 2019
• Study Completion: September 1, 2022
• Last Updated: September 29, 2022
• Results First Posted: January 13, 2022

Record last verified: 2022-09

Locations

US (1)