MPDL3280A-imaging-IST-UMCG

ImmunoPET Imaging With 89Zr-MPDL3280A in Patients With Locally Advanced or Metastatic Solid Tumors Prior to and During MPDL3280A Treatment

NCT02453984•University Medical Center Groningen

View on ClinicalTrials.gov

Summary

By performing a 89Zr-MPDL3280A-PET scan prior or during treatment with MPDL3280A, the uptake of the tracer in the primary and metastatic tumor lesions and normal organ distribution can be evaluated, as well as the use of a 89Zr-MPDL3280A-PET as a complementary tool for patient selection and MPDL3280A- target saturation during treatment.

Detailed Description

The Programmed cell death protein 1 (PD1)/Programmed death-ligand 1 (PD-L1) axis is an important immune checkpoint for T cell activation that is used by tumors to evade the host immune response. Blocking signaling with the PD-L1 antibody MPDL3280A results in ongoing T cell activity and can induce durable tumor regression across numerous solid tumor types. PD-L1 is not only expressed by tumor cells but also by immune cells, activated vascular endothelial cells and in immune privileged sites such as the eye. An obstacle to using PD-L1 expression as predictive biomarker might be its potential heterogeneous expression and fast dynamics. For PD1/PD-L1 pathway inhibition PD-L1 tumor surface expression, positive in 40-100% of all melanoma patients and 35-95% of all non-small-cell lung cancer (NSCLC) patients, was proposed as a potential biomarker. In early clinical trials, PD-L1 expression has been associated with response to PD1/PD-L1 inhibition. However, other clinical trials reported response to PD1/PD-L1 checkpoint inhibitors in up to 47% of PD-L1-negative melanomas assessed by a single biopsy. In bladder cancer weak to strong PD-L1 expression has been reported in 30% of the patients, however also response in PD-L1-negative patients has been seen. For triple-negative breast cancer (TNBC) little is known, but early response data are also very promising. Radio-labeling of MPDL3280A with the positron emission tomography (PET) radionuclide Zirconium-89 (89Zr) enables non-invasive imaging and quantification of PD-L1 distribution in cancer patients. By performing a 89Zr-MPDL3280A-PET scan prior to treatment with MPDL3280A, the uptake of the tracer in the primary and metastatic tumor lesions and normal organ distribution can be evaluated, as well as the use of a 89Zr-MPDL3280A-PET as a complementary tool for patient selection in the future. There is currently no information with regards to tumor saturation or inflammation induced by checkpoint inhibitors. This can be measured with SUV of 89Zr-MPDL3280A PET changes during a therapeutic dosing with MPDL3280A.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Histologically or cytologically documented locally advanced or metastatic solid tumors whom in the opinion of the investigator, based on available clinical data may benefit from treatment with anti-PD-L1.
•2. Tumor lesion(s) of which a histological biopsy can safely be obtained according to standard clinical care procedures.
•3. ECOG performance status of 0 or 1.
•4. Life expectancy ≥12 weeks.
•5. Signed Informed Consent Form.
•6. Ability to comply with protocol.
•7. Age ≥18 years.
•8. Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions.
•9. Adequate hematologic and end organ function, defined by the following laboratory results obtained within ≤14 days prior to 89Zr-MPDL3280A injection:
•* ANC ≥1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to 89Zr-MPDL3280A injection).
+11 more criteria

Exclusion Criteria

•1. Any approved anti-cancer therapy, including chemotherapy or hormonal therapy within ≤14 days prior to 89Zr-MPDL3280A injection; the following exceptions are allowed:
•* Hormone-replacement therapy or oral contraceptives.
•* TKIs approved for treatment of NSCLC discontinued \>7 days prior to tracer injection. The baseline scan must be obtained after discontinuation of prior TKIs.
•2. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to the 89Zr-MPDL3280A injection.
•3. Unstable brain metastases.
•4. Unstable leptomeningeal disease.
•5. Uncontrolled tumor-related pain.
•* Patients 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. Patients 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.
+41 more criteria

Locations (1)

University Medical Center Groningen

Groningen, Netherlands

Key Dates

Start Date

February 24, 2016

Primary Completion Date

November 23, 2020

Completion Date

June 1, 2024

Last Updated

May 3, 2024

Enrollment

ACTUAL participants

Conditions

Locally Advanced or Metastatic Solid Tumors Irrespective of PD-L1 Expression

Interventions

89Zr-MPDL-3280A-PET scans

OTHER