Nivolumab + 177Lu-girentuximab for Kidney Cancer

Recruiting at 8 trial locations

Overseen By Darren Feldman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

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

Compensation: Varies

Number of Visits: Unknown

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two treatments, 177Lu-girentuximab (a radiolabeled antibody therapy) and nivolumab (an immunotherapy drug), is effective and safe for individuals with advanced kidney cancer, specifically clear cell renal cell carcinoma. The study targets patients whose cancer expresses a protein called CAIX. It seeks participants with kidney cancer that is inoperable or has metastasized, and who have undergone at least one unsuccessful treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that nivolumab is well-tolerated in patients with advanced kidney cancer. It is an FDA-approved treatment with a known safety profile, meaning its side effects are well-documented. Common side effects include fatigue and skin rash.

In contrast, researchers are still studying the safety of 177Lu-labeled-girentuximab. This targeted therapy focuses on cancer cells with a protein called CAIX. As it is in the earlier stages of research, less safety information is available. The current trial aims to find the highest dose patients can tolerate without serious side effects, carefully monitoring and adjusting doses to ensure participant safety.

Overall, more safety information is available for nivolumab, while 177Lu-labeled-girentuximab is still under study to better understand its effects on people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Nivolumab combined with 177Lu-labeled-girentuximab for kidney cancer because it offers a novel approach by pairing a targeted radioimmunotherapy with an immune checkpoint inhibitor. Unlike traditional treatments like surgery or the standard use of drugs like sunitinib, this combination aims to deliver radiation directly to cancer cells while also boosting the body's immune response. The 177Lu-labeled-girentuximab specifically targets renal cancer cells, potentially reducing damage to healthy tissues, while Nivolumab helps the immune system recognize and attack the cancer more effectively. This dual-action strategy could enhance treatment efficacy and offer new hope for patients with advanced or metastatic clear cell renal cell carcinoma.

What evidence suggests that the combination of 177Lu-girentuximab and nivolumab could be an effective treatment for kidney cancer?

This trial will evaluate the combination of 177Lu-girentuximab and nivolumab for treating advanced clear cell renal cell carcinoma (ccRCC), a type of kidney cancer. Research shows that 177Lu-girentuximab targets a protein called CAIX, often found in ccRCC tumors, delivering radiation directly to the cancer cells, which may improve treatment results. Nivolumab, an immunotherapy drug, has shown effectiveness in shrinking tumors in previously treated advanced kidney cancer. Early results suggest that using these two treatments together could be very effective for ccRCC, but more research is needed to fully understand the benefits. Participants in this trial will receive both treatments to assess their combined effectiveness. ^{1 6 7 8 9}

Who Is on the Research Team?

Darren R. Feldman

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-labeled-girentuximab
• Nivolumab

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07197580

Study of 177Lu-TLX250 in Advanced Relapsed or ... This is a randomized, open-label, multi-center 3 study evaluating the safety and efficacy of 177Lu-TLX250, a CAIX-targeting radioligand therapy, in adult ...

2. telixpharma.com telixpharma.com/news-views/zircon-phase-iii-kidney-cancer-imaging-study-presented-at-aua-new-data-confirms-efficacy-in-masses-2cm-or-smaller/

ZIRCON Phase III Kidney Cancer Imaging Study ... New data presented demonstrates the high value of TLX250-CDx PET/CT imaging in detecting ccRCC, with secondary analysis confirming utility and effectiveness in ...

3. urologytimes.com urologytimes.com/view/darren-feldman-md-on-study-of-177lu-girentuximab-plus-nivolumab-for-ccrcc

Darren Feldman, MD, on study of 177Lu-girentuximab plus ... The phase 2 STARLITE 2 trial is assessing 177Lu-girentuximab plus nivolumab in advanced clear cell renal cell carcinoma.

4. oncologynewscentral.com oncologynewscentral.com/drugs/info/fda-rejects-kidney-cancer-drug

FDA Rejects Kidney Cancer Drug According to Telix, TLX250-CDx produces images with a “high tumor-to-background ratio and high intra- and inter-reader consistency” by binding ...

5. targetedonc.com targetedonc.com/view/fda-grants-priority-review-to-tlx250-cdx-in-kidney-cancer

FDA Grants Priority Review to TLX250-CDx in Kidney ... The FDA accepted and granted priority review to the BLA of TLX250-CDx for the potential treatment of patients with clear cell renal cell carcinoma (ccRCC).

6. cancernetwork.com cancernetwork.com/view/fda-grants-priority-review-to-tlx250-cdx-in-clear-cell-rcc-imaging

FDA Grants Priority Review to TLX250-CDx in Clear Cell ... Data from the phase 3 ZIRCON study support the biologics license application for TLX250-CDx in clear cell renal cell carcinoma imaging.

7. auntminnie.com auntminnie.com/clinical-news/molecular-imaging/news/15754218/fda-rejects-telixs-bla-for-kidney-cancer-investigational-pet-agent

FDA rejects Telix's BLA for kidney cancer investigational ... TLX250-CDx is a PET agent developed to diagnose and characterize clear cell renal cell carcinoma (ccRCC), the most common and one of the ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03849118

Study Details | NCT03849118 | 89Zr-TLX250 for PET/CT ... Study Overview. Brief Summary. 89Zr-TLX250 is under clinical development as a diagnostic agent targeting clear cell renal cell carcinoma.

9. telixpharma.com telixpharma.com/wp-content/uploads/2024/01/TLX_JP_Morgan_Healthcare_Conference_Presentation.pdf

11, 2024 ASX: TLX Clear cell renal cell carcinoma. 2. Muz et al. Hypoxia (Auckl). 2015. Page 21. CAIX expression is associated with poor clinical outcomes.