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

Phase 2

Completed

• Conditions: cancer; solid tumors; 10027655

• Registration Number: NL-OMON47630
• Lead Sponsor: niversitair Medisch Centrum Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• 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 trail (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: Patients 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: Patients 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.
- Patients 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).
Patients 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:
- Patients with documented liver metastases: AST and/or ALT <= 5 × ULN
- Patients with documented liver or bone metastases: alkaline phosphatase <= 5 × ULN
•Serum bilirubin <= 1.5 × ULN. Patients with known Gilbert disease who have serum bilirubin level <= 3 × ULN may be enrolled.
•INR and aPTT <= 1.5 × ULN. This applies only to patients who are not receiving therapeutic anticoagu

Exclusion Criteria

1.Any approved anti-cancer therapy, including chemotherapy or hormonal therapy within <=21 days prior to the first full dose of MPDL3280A.
•Hormone-replacement therapy or oral contraceptives.
•TKIs approved for treatment of NSCLC discontinued >7 days prior to the first full dose of MPDL3280A. The baseline scan must be obtained after discontinuation of prior TKIs.
2.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.
3.Unstable brain metastases.
4.Unstable leptomeningeal disease.
5.Uncontrolled tumor-related pain.
•Subjects requiring pain medication must be on a stable regimen at study entry.
•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.
•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.
6.Uncontrolled pleural effusion, pericardial effusion, or 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. •Subjects, who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
•Subjects who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study.
8. A second malignancy within 5 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the 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, or 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 the 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.
•Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
•Subjects with controlled Type I diabetes mellitus on a stable dose of in

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Response to MPDL3280A therapy as measured by ORR according to standard RECIST<br /><br>v1.1, defined as the proportion of patients whose best overall response is<br /><br>either a partial response (PR) or complete response (CR), as assessed by the<br /><br>investigator.</p><br>