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 trial aims to evaluate how effectively a special scan, called 89Zr-DFO-Atezolizumab PET/CT, can identify and assess kidney cancer. Researchers seek to determine if this scan can reveal the presence of a specific protein, PD-L1, and predict the cancer's response to certain immune therapies. The trial includes two groups: one with non-metastatic kidney cancer, who will undergo the scan before surgery, and another with metastatic cancer, who will receive the scan before starting treatment. The trial seeks participants with kidney cancer who plan to undergo surgery or immunotherapy and can remain still for a 30-60 minute scan. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

What prior data suggests that this imaging technique is safe for patients with kidney cancer?

Research has shown that atezolizumab has been studied for its safety in treating kidney cancer. Atezolizumab is usually well-tolerated, with common side effects such as tiredness, nausea, and itching. More serious side effects are rare but can occur, including the immune system mistakenly attacking healthy cells.

The use of 89Zr-DFO-atezolizumab, which combines atezolizumab with a small amount of radioactive material for imaging, is less common. Specific safety information for 89Zr-DFO-atezolizumab is limited, but existing safety data for atezolizumab is reassuring.

This trial is in Phase 2, indicating that some safety information from earlier studies is available. However, more data is needed to fully understand the treatment's safety. Participants should discuss any concerns or questions with the trial team or their doctor before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they offer a novel way to tackle kidney cancer. Unlike standard treatments like surgery, radiation, or traditional drug therapies, 89Zr-DFO-Atezolizumab combines a powerful imaging tool with an immune checkpoint inhibitor, allowing doctors to visualize and target tumors more effectively. This dual approach not only enhances the precision of treatment but also has the potential to improve outcomes for patients with both localized and metastatic renal cell carcinoma (RCC). By focusing on the body's immune response, these treatments aim to provide a more personalized and potentially more effective option for kidney cancer patients.

What evidence suggests that this imaging technique is effective for kidney cancer?

Studies have shown that 89Zr-DFO-Atezolizumab, an investigational treatment in this trial, can help visualize PD-L1 expression in kidney cancer. This ability to identify protein levels is crucial, as higher PD-L1 levels in tumors are linked to worse outcomes. Research indicates this approach can guide treatment decisions. Atezolizumab, another treatment option in this trial, is an immune therapy that has demonstrated a good response rate, with about 33% of patients with clear cell kidney cancer experiencing tumor shrinkage. In some patients, it can extend overall survival, offering hope for longer life expectancy. ^{2 6 7 8 9}

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]

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 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]

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]

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]

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

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NCT04006522 | 89Zr-DFO-Atezolizumab ImmunoPET/CT ... This is an exploratory analysis correlating 89Zr-DFO-Atezolizumab uptake with PD-L1 immunohistochemical (IHC) analyses in locally advanced kidney cancer (cohort ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9669181/

ImmunoPET Imaging with 89Zr-labeled Atezolizumab Enables ... ImmunoPET imaging with 89 zr-labeled atezolizumab enables in vivo evaluation of PD-L1 in tumorgraft models of renal cell carcinoma.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.6_suppl.TPS759

An exploratory study of 89Zr-DFO-Atezolizumab ... An exploratory study of 89Zr-DFO-Atezolizumab ImmunoPET/CT in patients with locally advanced or metastatic renal cell carcinoma. Authors: I.

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PD-L1 detection using 89Zr-atezolizumab immuno-PET in ... Programmed death-ligand 1 (PD-L1) expression in metastatic renal cell carcinoma (RCC) correlates with a worse prognosis, but whether it also ...

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89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With ... This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab Positron Emission Tomography/Computed Tomography (PET/CT) scans in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32245328/

Atezolizumab for the treatment of renal cell carcinoma In this manuscript, we summarize the preclinical, clinical, and safety data on atezolizumab for treatment of renal cell carcinoma and describe ongoing trials.

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)03949-7/fulltext

LBA66 IMmotion010: Efficacy and safety from the phase III ... Efficacy and safety from the phase III study of atezolizumab (atezo) vs placebo (pbo) as adjuvant therapy in patients with renal cell carcinoma (RCC)

8. aacrjournals.org aacrjournals.org/clincancerres/article/28/22/4907/710453/ImmunoPET-Imaging-with-89Zr-Labeled-Atezolizumab

ImmunoPET Imaging with 89 Zr-Labeled Atezolizumab ... ImmunoPET using 89Zr-labeled atezolizumab allowed noninvasive real-time measurement of PD-L1 in an RCC patient-derived tumorgraft platform, which supported an ...

9. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/rcc/a-study-of-atezolizumab-as-adjuvant-therapy-in-participants-with.html

Clinical Trial – Renal Cell Carcinoma – Safety and Effica... A Clinical Trial of Atezolizumab in Patients with. Renal Cell Carcinoma that is at High Risk of Coming Back After Surgery (IMmotion010).