MPDL3280A treatment in patients with locally advanced or metastatic solid tumors after or during investigational imaging

Phase 1

Conditions: solid tumors
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-000907-19-NL

Lead Sponsor: niversity Medical Center Groningen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 98

Inclusion Criteria

1.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
2.Participation within the 18F-IL2 imaging trial (IL2-imaging-IST-UMCG) or 89Zr-MPDL3280A antibody imaging trial (MPDL3280A-imaging-IST-UMCG) or CD8 imaging trial (ZED88082-img-UMCG-2018) before participation in the MPDL3280A treatment trial.
3.Assessment of the PD-L1-tumor status of a fresh tumor biopsy as determined by an IHC assay based on PD-L1 expression on immunocells and/or tumor cells performed by a central laboratory, performed as part of one of the investigational imaging trials.
4.Patients 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:
oPatients with disease progression during or following platinum-based adjuvant/neoadjuvant chemotherapy are eligible if = 12 months have elapsed between the last treatment administration and the date of recurrence.
•Additional criteria for NSCLC:
oPatients with disease progression during or following platinum-based adjuvant/neoadjuvant chemotherapy or concurrent chemoradiation for NSCLC are eligible if = 6 months have elapsed between the last treatment administration and the date of recurrence.
oPatients 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).
oPatients with a known Anaplastic Lymphoma Kinase (ALK) fusion oncogene must also have experienced disease progression (during or after treatment) or intolerance to treatment with crizotinib or another ALK inhibitor.
5.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6.Life expectancy =12 weeks.
7.Signed Informed Consent Form.
8.Ability to comply with protocol.
9.Age =18 years.
10.Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions.
11.Adequate hematologic and end organ function, defined by the following laboratory results obtained within =28days prior to the first full dose of MPDL3280A:
•ANC =1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
•WBC counts >2500/µL
•Lymphocyte count =500/µL
•Platelet count =100,000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
•Hemoglobin =9.0 g/dL. Patients may be transfused or receive erythropoietic treatment to meet this criterion.
•AST, ALT, and alkaline phosphatase = 2.5× the upper limit of normal (ULN), with the following exceptions:
oPatients with documented liver metastases: AST and/or ALT = 5 × ULN

Exclusion Criteria

1.Any approved anti-cancer therapy, including chemotherapy or hormonal therapy within =21 days prior to first full dose MPDL3280A
2.Treatment with any other investigational agent, other than investigational tracer 89Zr-MPDL3280A, 18F-FB-IL2 or 89Zr-CD8-imaging, or participation in another trial with therapeutic intent within 28 days prior to first full dose MPDL3280A
3.Unstable brain metastases
4.Unstable leptomeningeal disease
5.Uncontrolled tumor-related pain
6.Uncontrolled pleural effusion, pericardial effusion, ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed
7.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
8. A second malignancy within 5 years prior to Cycle 1 Day 1, with exception of those with negligible risk of metastasis or death treated with expected curative outcome (adequately treated carcinoma in situ of cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ treated surgically with curative intent)
9.Pregnant and lactating women
10.History of severe allergic, anaphylactic, other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
11.Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cell products or any component of MPDL3280A formulation
12.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.
• history of autoimmune-related hypothyroidism on stable dose of thyroid replacement hormone may be eligible
• controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible
• eczema, psoriasis, lichen simplex chronicus, vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided they meet following conditions:
o Rash must cover less than 10% BSA
o Disease well controlled at baseline and only requiring low potency topical steroids
o No acute exacerbation of underlying condition within the previous 12 months (not requiring PUVA, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
13.History of idiopathic pulmonary fibrosis, organizing pneumonia (bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
14.Serum albumin < 2.5 g/dL
15.Positive test for HIV
16.Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
17.Active tuberculos

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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