ImmunoPET/CT Imaging for Kidney Cancer

Overseen By Kelli Key, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Orhan Kemal Oz

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Severe allergies, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab Positron Emission Tomography/Computed Tomography (PET/CT) scans in patients with locally advanced or metastatic renal cell carcinoma (RCC). This open label, nontherapeutic trial will test the correlation of 89Zr-DFO-Atezolizumab immunoPET/CT with programmed death-ligand 1 (PD-L1) expression and the response to immune checkpoint inhibitor therapy in patients with RCC. There will be two cohorts, one made up of patients with localized RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to nephrectomy and a second cohort of patients with metastatic RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to treatment with an immune checkpoint inhibitor.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on significant autoimmune disease treatment with high-dose steroids or other immunosuppressive agents, you may not be eligible to participate.

Is atezolizumab safe for humans?

Atezolizumab, used in cancer treatment, is generally considered safe but can cause immune-related side effects like inflammation in the kidneys and other organs. These side effects are usually rare and can often be managed with medications like steroids. ^{1 2 3 4 5}

How does the treatment differ from other treatments for kidney cancer?

This treatment uses ImmunoPET/CT imaging with 89Zr-labeled atezolizumab to non-invasively detect PD-L1 expression in kidney cancer, offering a real-time and comprehensive assessment compared to traditional biopsy methods. This approach can help predict patient response to immunotherapy, which is not possible with standard tissue-based diagnostics. ^{6 7 8 9 10}

What data supports the effectiveness of the drug 89Zr-DFO-Atezolizumab (Tecentriq) for kidney cancer?

Research shows that atezolizumab, a part of the treatment, has been effective in improving progression-free survival in patients with certain types of kidney cancer when used with another drug, bevacizumab. This suggests that atezolizumab can be beneficial in treating kidney cancer. ^{1 3 8 10 11}

Who Is on the Research Team?

James Brugarolas, MD, PhD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic kidney cancer who can consent to the study, are not pregnant, and do not have severe allergies to atezolizumab. Participants must be able to lie still for a PET/CT scan and should either be planned for kidney surgery or about to start immune therapy.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent.

I can stay still for up to an hour for a scan.

I am diagnosed with or suspected to have kidney cancer and am planning surgery or have confirmed metastatic kidney cancer.

Exclusion Criteria

I am on high-dose steroids or other drugs for an autoimmune disease.

I am unable to understand and give consent for my treatment.

ICI therapy is not suitable for me due to other health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Pre-Treatment Evaluation

Participants undergo 89Zr-DFO-Atezolizumab PET/CT scans to assess PD-L1 expression and prepare for subsequent treatment or surgery

4 weeks

1-2 visits (in-person)

Follow-up

Participants are monitored for signs of recurrence or progression of their cancer, with repeat PET scans offered

Up to 5 years

Periodic visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 89Zr-DFO-Atezolizumab
• Atezolizumab

Trial Overview The trial tests if a special type of PET/CT scan using 89Zr-DFO-Atezolizumab can show how much PD-L1 protein is in the tumor and predict response to immune checkpoint inhibitors. It includes two groups: one undergoing surgery and another starting immunotherapy.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 2 Interventions

Patients with Unresectable/Metastatic RCC prior to treatment with an immune checkpoint inhibitor.

Group II: Cohort 1 Experimental Treatment 2 Interventions

Patients with Localized RCC prior to nephrectomy.

Who Is Running the Clinical Trial?

Orhan Kemal Oz

Lead Sponsor

Trials

2

Recruited

80+

James Brugarolas

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

In the IMmotion150 study involving 305 patients with previously untreated metastatic renal cell carcinoma, atezolizumab (both alone and in combination with bevacizumab) demonstrated a delayed time to deterioration in symptoms and fatigue compared to sunitinib, indicating better patient-reported outcomes.

Atezolizumab monotherapy showed the most significant improvement in maintaining daily function and reducing symptom severity, suggesting it may be a more effective treatment option than sunitinib for managing symptoms in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in a phase 2 study comparing atezolizumab alone or with bevacizumab vs sunitinib in previously untreated metastatic renal cell carcinoma. Pal, SK., McDermott, DF., Atkins, MB., et al.[2021]

The phase I study involving 10 patients showed that [89Zr]Zr-DFO-girentuximab is safe and well tolerated, with no serious treatment-related adverse events reported, indicating its potential for clinical use.

89Zr-girentuximab PET/CT imaging effectively differentiated clear cell renal cell carcinoma (ccRCC) from non-ccRCC lesions in all patients, providing a quantitative assessment of tumor dosimetry, which is crucial for treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study to assess safety, biodistribution and radiation dosimetry for 89Zr-girentuximab in patients with renal cell carcinoma. Merkx, RIJ., Lobeek, D., Konijnenberg, M., et al.[2022]

Novel molecular imaging techniques like SPECT/CT and PET-CT are being developed to improve the preoperative diagnosis of renal cell carcinoma, which could help reduce postoperative complications and preserve kidney function.

Research shows that 99mTc-sestamibi SPECT/CT offers quick results with high specificity and sensitivity for distinguishing between benign and malignant lesions, while girentuximab PET-CT provides superior image quality, highlighting the need for further studies to validate these findings for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Imaging Diagnosis of Renal Cancer Using 99mTc-Sestamibi SPECT/CT and Girentuximab PET-CT-Current Evidence and Future Development of Novel Techniques. Tataru, OS., Marchioni, M., Crocetto, F., et al.[2023]

Atezolizumab, a PD-L1 antibody, showed a manageable safety profile in 70 patients with metastatic renal cell carcinoma (RCC), with only 17% experiencing grade 3 treatment-related adverse events and no severe (grade 4 or 5) events reported.

The treatment demonstrated promising clinical activity, with a median overall survival of 28.9 months and an objective response rate of 15%, particularly higher in patients with specific tumor characteristics, suggesting potential biomarkers for predicting response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study. McDermott, DF., Sosman, JA., Sznol, M., et al.[2022]

In the final analysis of the IMmotion151 trial involving 915 patients with untreated metastatic renal cell carcinoma, the combination of atezolizumab and bevacizumab did not show a significant improvement in overall survival compared to sunitinib, with median survival times of 36.1 months versus 35.3 months, respectively.

However, patients with specific tumor characteristics (T-effector/proliferative, proliferative, or small nucleolar RNA profiles) showed improved overall survival trends with the combination therapy, suggesting that certain biomarker profiles may help identify those who could benefit more from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. Motzer, RJ., Powles, T., Atkins, MB., et al.[2022]

Atezolizumab, an immune checkpoint inhibitor targeting PD-L1, has shown efficacy in treating advanced urothelial carcinoma without the renal toxicity commonly associated with other ICIs.

In a case study, a patient with metastatic renal cell carcinoma experienced acute interstitial nephritis after treatment with atezolizumab and bevacizumab, but their renal function completely recovered following steroid therapy, highlighting the potential for manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute tubulointerstitial nephritis associated with atezolizumab, an anti-programmed death-ligand 1 (pd-l1) antibody therapy. Xipell, M., Victoria, I., Hoffmann, V., et al.[2021]

In the phase III IMmotion151 trial involving 915 patients with previously untreated metastatic renal cell carcinoma, the combination of atezolizumab and bevacizumab resulted in significantly lower treatment burden and better patient-reported outcomes compared to sunitinib.

Patients receiving atezolizumab plus bevacizumab reported milder symptoms, less interference in daily life, and improved health-related quality of life, with a notable reduction in the time to deterioration for core symptoms and overall quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes from the Phase III Randomized IMmotion151 Trial: Atezolizumab + Bevacizumab versus Sunitinib in Treatment-Naïve Metastatic Renal Cell Carcinoma. Atkins, MB., Rini, BI., Motzer, RJ., et al.[2023]

Atezolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, can cause rare but serious immune-related adverse events (irAEs) such as acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP).

In a case study of a patient receiving atezolizumab, the development of AKI and ITP occurred one week after treatment initiation, but with appropriate management including IVIG and steroids, the patient's condition improved and was discharged for routine follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. Yılmaz, A., Mirili, C., Bilici, M., et al.[2022]

ImmunoPET using [89Zr]Zr-DFO-ATZ showed a strong correlation with traditional PD-L1 detection methods (IHC), indicating its potential as a reliable noninvasive tool for assessing PD-L1 expression in metastatic renal cell carcinoma (RCC).

The study suggests that the PD-L1 signal detected by immunoPET may influence the effectiveness of immune checkpoint inhibitors, with ongoing clinical trials further exploring its predictive power for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ImmunoPET Imaging with 89Zr-Labeled Atezolizumab Enables In Vivo Evaluation of PD-L1 in Tumorgraft Models of Renal Cell Carcinoma. Mulgaonkar, A., Elias, R., Woolford, L., et al.[2023]

The study developed and optimized [89Zr]-Atezolizumab for PET imaging, which allows for noninvasive detection of PD-L1 expression in triple-negative breast cancer (TNBC) tumors, potentially improving treatment monitoring.

Imaging results showed that PD-L1 expression increased after certain therapies, indicating that this method could help assess tumor heterogeneity and response to treatment over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[89Zr]-Atezolizumab-PET Imaging Reveals Longitudinal Alterations in PDL1 during Therapy in TNBC Preclinical Models. Massicano, AVF., Song, PN., Mansur, A., et al.[2023]

In a first-in-human study involving 22 patients with various tumor types, PET imaging using zirconium-89-labeled atezolizumab showed promise in predicting responses to PD-L1 blockade therapy, with better correlation to clinical outcomes than traditional biopsy-based methods.

The imaging revealed high and heterogeneous uptake of the tracer in tumors, suggesting that molecular PET imaging could be a more effective tool for assessing PD-L1 status and guiding treatment decisions compared to current diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Bensch, F., van der Veen, EL., Lub-de Hooge, MN., et al.[2019]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in a phase 2 study comparing atezolizumab alone or with bevacizumab vs sunitinib in previously untreated metastatic renal cell carcinoma. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Phase I study to assess safety, biodistribution and radiation dosimetry for 89Zr-girentuximab in patients with renal cell carcinoma. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Imaging Diagnosis of Renal Cancer Using 99mTc-Sestamibi SPECT/CT and Girentuximab PET-CT-Current Evidence and Future Development of Novel Techniques. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab, an Anti-Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Acute tubulointerstitial nephritis associated with atezolizumab, an anti-programmed death-ligand 1 (pd-l1) antibody therapy. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes from the Phase III Randomized IMmotion151 Trial: Atezolizumab + Bevacizumab versus Sunitinib in Treatment-Naïve Metastatic Renal Cell Carcinoma. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

ImmunoPET Imaging with 89Zr-Labeled Atezolizumab Enables In Vivo Evaluation of PD-L1 in Tumorgraft Models of Renal Cell Carcinoma. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

[89Zr]-Atezolizumab-PET Imaging Reveals Longitudinal Alterations in PDL1 during Therapy in TNBC Preclinical Models. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. [2019]