Clinical Trial · NCT02478099

MPDL3280A-treatment-IST-UMCG

Overview

To be able to evaluate the investigational imaging - 89Zr-MPDL3280A-PET, 89Zr-CD8 imaging and 18F-FB-IL2-PET - as complementary tools for selection of patients to be treated with MPDL3280A, within this treatment trial the investigators will assess safety, tolerability and anti-tumor activity of MPDL3280A in cancer patients, who have undergone investigational imaging.

Sponsor

University Medical Center Groningen

Phase

Phase 2

Contacts

Elisabeth de Vries, Professor (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT02478099

Eligibility

Inclusion

For female subjects of childbearing potential and male subjects with partners of childbearing potential, agreement (by subject and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\< 1% per year\] when used consistently and correctly) and to continue its use for 6 months after the last dose of MPDL3280A.
Subjects with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN.
Adequate hematologic and end organ function, defined by the following laboratory results obtained within ≤28 days prior to the first full dose of MPDL3280A:
Subjects are eligible if disease progression during or following first-line chemotherapy or any subsequent treatment lines for locally advanced or metastatic solid tumor whom, in the opinion of the investigator, based on available clinical data, may benefit from treatment with anti PD-L1 immunotherapy . ● Additional criteria for cancer of the urinary tract:
Hemoglobin ≥9.0 g/dL. Subjects may be transfused or receive erythropoietic treatment to meet this criterion.
Histologically or cytologically documented locally advanced or metastatic solid tumor, whom in the opinion of the investigator, based on available clinical data, may benefit from treatment with anti PD-L1 immunotherapy .
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Serum bilirubin ≤ 1.5 × ULN. Subjects with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled.
INR and aPTT ≤ 1.5 × ULN. This applies only to subjects who are not receiving therapeutic anticoagulation; subjects receiving therapeutic anticoagulation should be on a stable dose.
Participation within the 18F-IL2 imaging trial (IL2-img-UMCG-2015) or 89Zr-MPDL3280A antibody imaging trial (MPDL3280A-img-042015) or CD8 imaging trial (ZED88082-img-UMCG-2018) before participation in the MPDL3280A treatment trial.
Subjects with documented liver metastases: AST and/or ALT ≤ 5 × ULN.
AST, ALT, and alkaline phosphatase ≤ 2.5× the upper limit of normal (ULN), with the following exceptions:
Subject must have undergone a fresh tumor biopsy for PD-L1 assessment performed as part of one of the investigational imaging trials.
Life expectancy ≥12 weeks.
WBC counts \>2500/μL.
Creatinine clearance ≥ 30 mL/min
Ability to comply with protocol.
Lymphocyte count ≥500/μL.
Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions.
ANC ≥1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1).
Subjects with a known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene must also have experienced disease progression (during or after treatment) or intolerance to treatment with erlotinib, gefitinib, or another EGFR tyrosine kinase inhibitor (TKI).
Platelet count ≥100,000/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1).

Exclusion

Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. ● Influenza vaccination should be given during influenza season only (example: approximately October to March in the Northern Hemisphere). Subjects must not receive live, attenuated influenza vaccine (e.g. FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study treatment of within 5 months after the last dose of MPDL3280A.
Subjects with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C.
Treatment with any other investigational agent, other than the investigational tracer 89Zr-MPDL3280A, 18F-FB-IL2 or 89Zr-CD8-imaging, or participation in another clinical trial with therapeutic intent within 28 days prior to the first full dose of MPDL3280A.
Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
Disease is well controlled at baseline and only requiring low potency topical steroids.
Positive test for HIV.
Minimum of 6 weeks from the last dose of anti-CTLA-4
Unstable brain metastases.
Any approved anti-cancer therapy, including chemotherapy or hormonal therapy within ≤21 days prior to the first full dose of MPDL3280A; the following exceptions are allowed:
Uncontrolled hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \>12 mg/dL or corrected serum calcium \>ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
Rash must cover less than 10% of body surface area (BSA).
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
Subjects with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Subjects with indwelling catheters (e.g., PleurX) are allowed.
The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g. fludrocortisone) for subjects with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to Cycle 1, Day 1.
Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cell products or any component of the MPDL3280A formulation.
Severe infections within 4 weeks prior to the first full dose of MPDL3280A, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
Serum albumin \< 2.5 g/dL.
Treatment with systemic immunostimulatory agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to the first full dose of MPDL3280A.
Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
Hormone-replacement therapy or oral contraceptives.
Subjects with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of HBsAg) are eligible. HBV DNA test must be performed in these subjects prior to Cycle 1, Day 1.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment. Subjects should be recovered from the effects of radiation. There is no required minimum recovery period.
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies. ● Subjects who have had prior anti-CTLA-4 treatment may be enrolled, provided the following requirements are met:
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina. ● Subjects with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \<50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1. ● Subjects receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
Subjects requiring pain medication must be on a stable regimen at study entry.
Unstable leptomeningeal disease.
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Prior allogeneic bone marrow transplantation or solid organ transplant.
Pregnant and lactating women.
No history of severe immune related adverse effects from anti-CTLA-4 (CTCAE Grade 3 and 4)
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
No acute exacerbation of underlying condition within the previous 12 months (not requiring PUVA \[psoralen plus ultraviolet A radiation\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids).
Active tuberculosis.
Uncontrolled tumor-related pain.
Subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Subjects who have received acute, low-dose, systemic immunosuppressant medications (e.g. a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the sponsor.
Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.