Nivolumab + 177Lu-girentuximab for Kidney Cancer

Recruiting in Palo Alto (17 mi)

+8 other locations

Overseen by Darren R. Feldman

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Anti PD-1 or PD-L1

Must not be taking: Bisphosphonates, Denosumab

Disqualifiers: Brain metastases, Hypercalcemia, Cardiovascular disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for advanced kidney cancer using a specific protein. The treatment combines a drug that targets cancer cells with another drug that helps the body’s immune system fight the cancer. The goal is to see if this combination is safe and effective.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients on therapeutic anticoagulation should be on a stable dose, which suggests that some medications may be continued. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Nivolumab + 177Lu-girentuximab for kidney cancer?

A study on 177Lu-girentuximab showed that it helped stabilize the disease in 9 out of 14 patients with advanced kidney cancer, although some patients experienced significant side effects that limited further treatment. ^{1 2 3 4 5}

What makes the drug Nivolumab + 177Lu-girentuximab unique for kidney cancer?

This drug combines Nivolumab, which helps the immune system attack cancer cells, with 177Lu-girentuximab, a targeted therapy that delivers radiation directly to kidney cancer cells by binding to a specific protein (CAIX) on their surface. This dual approach aims to enhance treatment effectiveness by both boosting the immune response and directly targeting cancer cells with radiation. ^{1 2 3 4 5}

Research Team

Darren R. Feldman

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with advanced kidney cancer that has clear cell features and the CAIX protein. Participants must have had at least one prior systemic therapy, including an anti PD-1 or PD-L1 antibody, and cannot join if they've had certain treatments recently, have severe allergies to specific antibodies, uncontrolled infections like HIV or hepatitis B/C, untreated brain metastases larger than 1cm or symptomatic of any size, a history of significant cardiovascular disease within the past three months, or are pregnant.

Inclusion Criteria

Lymphocyte count ≥ 500/μL

INR and aPTT ≤ 1.5 x ULN

My platelet count is at least 100,000/μL without recent transfusions.

Exclusion Criteria

I have not had major surgery in the last 4 weeks.

I have brain metastases larger than 1cm or they are causing symptoms.

Exposure to murine or chimeric antibodies within the last 5 years

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Establish the maximal tolerated dose (MTD) of 177Lu-labeled-girentuximab in combination with standard-dose nivolumab using a 3+3 design

24 weeks

Phase 2 Treatment

Participants receive the combination treatment of 177Lu-girentuximab and nivolumab to assess efficacy at the MTD

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 177Lu-labeled-girentuximab (Cancer Vaccine)
• Nivolumab (Monoclonal Antibodies)

Trial Overview The study tests whether combining Nivolumab (an immunotherapy drug) with a radioactive drug called 177Lu-girentuximab is safe and works against kidney cancer. Patients will also undergo scans using another substance called 89Zr-girentuximab to see how the tumor responds.

Participant Groups

Group I: Safety lead-in Phase: Participants with Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC Experimental Treatment 4 Interventions

Participants have Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC. The protocol will start with a safety-lead in phase using a 3+3 design to establish the maximal tolerated dose (MTD) of 177Lu-labeled-girentuximab in combination with standard-dose nivolumab. The initial starting dose of 177Lu-labeled-girentuximab is 1804 MBq/m2 which is 75% of the single agent dose established in prior studies and will proceed as shown in the schema below. Once the MTD is established, a Simon two-stage optimal design will commence. 10 patients will be enrolled in the first stage and if no responses are observed, the study will be terminated. If 1 or more responses are observed in the first 10 patients, we will extend enrollment to a total of 29 patients (19 additional patients) in the second stage.

Group II: Phase 2 Participants Experimental Treatment 4 Interventions

Participants have Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCC. If 1 or more responses are observed in the first 10 patients, we will extend enrollment to a total of 29 patients (19 additional patients) in the second stage.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

Findings from Research

The study demonstrated that dual-labeled girentuximab can specifically target clear cell renal cell carcinoma (ccRCC) tissue, allowing for effective visualization of tumors during surgery using both radionuclide and fluorescence imaging techniques.

In a trial involving seven human kidney specimens, the maximum uptake of girentuximab in tumor tissue was significantly higher (up to 0.33% of the injected dose per gram) compared to normal kidney tissue (up to 0.04% ID/g), confirming its potential for precise tumor detection in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Dual-Modality Imaging in Renal Cell Carcinoma: An Ex Vivo Kidney Perfusion Study. Hekman, MC., Boerman, OC., de Weijert, M., et al.[2018]

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]

In the ARISER trial involving 864 patients with high-risk clear cell renal cell carcinoma (ccRCC), girentuximab did not show a statistically significant improvement in disease-free survival (DFS) or overall survival (OS) compared to placebo, indicating it may not be an effective adjuvant treatment.

Despite the lack of clinical benefit, the study reported a median DFS of 71.4 months for the girentuximab group, suggesting that patients may have longer survival times than expected, which poses challenges for future drug development in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma: The ARISER Randomized Clinical Trial. Chamie, K., Donin, NM., Klöpfer, P., et al.[2022]

In a phase 2 trial involving 14 patients with metastatic clear cell renal cell carcinoma, lutetium 177-girentuximab radioimmunotherapy led to disease stabilization in 9 patients (64%), indicating its potential efficacy in treating this challenging condition.

While the treatment was generally well tolerated, it caused significant myelotoxicity, leading to prolonged low blood cell counts that prevented some patients from receiving retreatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma. Muselaers, CH., Boers-Sonderen, MJ., van Oostenbrugge, TJ., et al.[2022]

Girentuximab (cG250) effectively targets carbonic anhydrase IX (CAIX) on renal cancer cells, and its labeling with 177Lu for radioimmunotherapy has been optimized to maintain immunoreactivity, crucial for effective treatment.

In vivo studies showed that tumor uptake of the radiolabeled cG250 was less than 10% ID/g, attributed to factors like necrotic areas, heterogeneous CAIX expression, and low vascularity, which may limit the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Radiolabeled Girentuximab In Vitro and In Vivo. Basaco, T., Pektor, S., Bermudez, JM., et al.[2023]

References

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

Targeted Dual-Modality Imaging in Renal Cell Carcinoma: An Ex Vivo Kidney Perfusion Study. [2018]

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

Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma: The ARISER Randomized Clinical Trial. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Radiolabeled Girentuximab In Vitro and In Vivo. [2023]