What side effects are associated with this type of intervention?

The most common treatments for kidney cancer, such as targeted radiation therapy (e.g., 177Lu-girentuximab) and immune checkpoint inhibitors (e.g., Nivolumab), have distinct side effect profiles. Targeted radiation therapy can cause fatigue, nausea, and localized pain or inflammation at the treatment site. Immune checkpoint inhibitors like Nivolumab can lead to immune-related adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Other common treatments, such as VEGFR inhibitors (e.g., sunitinib), often result in hypertension, hand-foot syndrome, and gastrointestinal disturbances. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for kidney cancer that involve immune checkpoint inhibitors and targeted therapies. Nivolumab, an immune checkpoint inhibitor that blocks PD-1, has been approved for advanced renal cell carcinoma, often in combination with other agents like ipilimumab. Additionally, targeted therapies such as axitinib, a VEGFR inhibitor, have been approved in combination with immune checkpoint inhibitors like pembrolizumab. While 177Lu-girentuximab, which targets the CAIX protein for radiation delivery, is still under investigation, similar targeted approaches have been explored in clinical trials.

What other types of research exist?

Promising novel alternatives for kidney cancer treatment in 2024 include: 1) Pembrolizumab plus Axitinib, which combines PD-1 inhibition with VEGF inhibition, showing efficacy in advanced renal cell carcinoma. 2) Atezolizumab plus Bevacizumab, targeting PD-L1 and VEGF, respectively, with positive outcomes in clinical trials. 3) Lenvatinib plus Pembrolizumab, combining a multi-kinase inhibitor with an immune checkpoint inhibitor, demonstrating significant efficacy in advanced renal cell carcinoma. These combinations offer different mechanisms of action and have shown promising results in recent studies.

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Cancer Vaccine

Nivolumab + 177Lu-girentuximab for Kidney Cancer

Phase 2

Recruiting

Led By Darren Feldman, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

KPS ≥ 70

At least one prior line of systemic therapy, including at least one prior treatment with anti PD-1 or PD-L1 antibody

Must not have

Major surgery within 4 weeks prior to enrollment

Active untreated metastases to the brain >1cm or symptomatic (of any size)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 (+/- 2) weeks

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include allergic reactions to treatment components, immune system-related issues affecting organs due to Nivolumab's action on the immune system; radiation-related side effects from the radioactive drugs may include nausea and damage to surrounding tissues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am mostly able to care for myself.

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I have had treatment before, including a therapy targeting PD-1 or PD-L1.

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I am 18 years old or older.

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I have a detectable cancer spread that can be measured on a special PET/CT scan.

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My kidney cancer is advanced, cannot be surgically removed, and shows clear cell features or CAIX expression.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I have been treated with 177Lu-girentuximab before.

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I have an active or chronic hepatitis B or C infection.

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I have untreated cancer spread to my spinal cord or around my brain.

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My pain is not well-managed and I don't have a stable pain control plan.

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I am allergic to girentuximab or DFO.

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My HIV is not well-controlled despite treatment.

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I stopped checkpoint inhibitor therapy because of side effects.

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I cannot receive nivolumab treatment for any reason.

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I need help with feeding or hydration due to stomach or bowel problems.

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I do not have serious heart problems like recent heart attacks or unstable heart conditions.

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I have not had a stroke or mini-stroke in the last 6 months.

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I have a serious wound, ulcer, or untreated bone fracture that is not healing.

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I haven't needed more than 10 mg of prednisone daily for autoimmune issues in the last 2 years.

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I have high calcium levels in my blood that require treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 (+/- 2) weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 (+/- 2) weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 (+/- 2) weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximal tolerated dose (MTD) of 177Lu-girentuximab

Overall Response Rate/ORR

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Safety lead-in Phase: Participants with Advanced or Metastatic Clear Cell Renal Cell Carcinoma/RCCExperimental Treatment4 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 ParticipantsExperimental Treatment4 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

FDA approved

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for kidney cancer include targeted radiation and immune checkpoint inhibition. Targeted radiation, such as 177Lu-girentuximab, delivers radiation directly to cancer cells expressing the CAIX protein, minimizing damage to healthy tissue. Immune checkpoint inhibitors like Nivolumab block the PD-1 protein on immune cells, preventing cancer cells from evading the immune system and allowing the immune system to attack the cancer. These treatments are significant for kidney cancer patients as they offer targeted, effective options with potentially better outcomes and fewer side effects.