Subcutaneous vs Intravenous Nivolumab for Kidney Cancer

(CheckMate-67T Trial)

Recruiting at 234 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Anti-PD-1, Anti-PD-L1, Anti-CTLA-4

Disqualifiers: CNS metastases, Active autoimmune, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

632 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the drug levels, efficacy, safety, and tolerability of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread. The purpose of this study's substudy is to evaluate drug level biocomparability of subcutaneous nivolumab manufactured using two different manufacturing processes.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are HIV-positive, you must continue your antiretroviral therapy while participating in the study.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are HIV-positive, you must continue your antiretroviral therapy while participating in the study.

What data supports the effectiveness of the drug Nivolumab for kidney cancer?

Research shows that Nivolumab, when used alone or in combination with other drugs, improves survival and response rates in patients with advanced kidney cancer compared to other treatments. It also tends to have fewer side effects, making it a promising option for treating this condition. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Nivolumab for kidney cancer?

Research shows that Nivolumab, when used with another drug called ipilimumab, led to better and longer-lasting responses in kidney cancer patients compared to another treatment called sunitinib. Additionally, Nivolumab alone improved survival in patients with advanced kidney cancer compared to another drug, everolimus. ^{1 2 3 4 5}

Is Nivolumab safe for humans?

Nivolumab, also known as Opdivo, has been associated with some immune-related side effects, such as lung inflammation and kidney issues, but these are generally manageable. In patients on hemodialysis, it has been used safely, although careful monitoring is recommended. ^{6 7 8 9 10}

Is nivolumab safe for humans?

Nivolumab, also known as Opdivo, has been associated with some immune-related side effects, such as lung inflammation and kidney issues, but these are generally manageable. In patients on hemodialysis, nivolumab has been used safely, although careful monitoring is recommended. ^{6 7 8 9 10}

What makes the drug Nivolumab unique for kidney cancer treatment?

Nivolumab is unique for kidney cancer treatment because it can be administered both subcutaneously (under the skin) and intravenously (into a vein), offering flexibility in how patients receive the drug. This is different from many other treatments that are typically given only one way. ^{1 11 12 13 14}

What makes the drug Nivolumab unique for kidney cancer treatment?

Nivolumab is unique for kidney cancer treatment because it can be administered both subcutaneously (under the skin) and intravenously (into a vein), offering flexibility in how patients receive the drug. This is different from many other treatments that are typically given only one way. ^{1 11 12 13 14}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with advanced or metastatic clear cell renal cell carcinoma who've had no more than two prior treatments. They must have a Karnofsky performance status of at least 70, measurable disease by RECIST v1.1, and agree to use contraception if needed. Exclusions include untreated brain metastases, active autoimmune diseases, certain HIV conditions, recent live vaccines, other cancers within 2 years, and previous treatment with specific immune-targeting drugs.

Inclusion Criteria

My last cancer treatment didn’t work or caused side effects, and it was within the last 6 months.

My kidney cancer cannot be cured with surgery or radiation, or it has spread to other parts.

My kidney cancer has been confirmed to have clear cell features, possibly with sarcomatoid traits.

Exclusion Criteria

I haven't had a serious illness like COVID-19 in the last month.

I am HIV positive but have been on ART for at least 4 weeks and will continue treatment.

I have an autoimmune disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either subcutaneous or intravenous nivolumab to evaluate drug levels, efficacy, safety, and tolerability

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nivolumab

Trial Overview The study compares the levels and effects of Nivolumab when given as a subcutaneous injection (under the skin) versus intravenously (into a vein). Participants will be randomly assigned to one of these methods to assess drug efficacy and safety in those previously treated for kidney cancer that has spread.

Participant Groups

Group I: Arm D Experimental Treatment 1 Intervention

Group II: Arm C Experimental Treatment 1 Intervention

Group III: Arm A Experimental Treatment 1 Intervention

Group IV: Arm B Active Control 1 Intervention

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

In a phase III trial, the combination of nivolumab and ipilimumab resulted in a higher response rate (over 41%) compared to sunitinib (26.5%) in patients with intermediate or high-risk renal cell carcinoma.

Patients treated with the immunotherapy combination not only had longer progression-free survival but also experienced fewer side effects, indicating a potentially safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint Inhibitor Combo Effective for RCC. [2019]

In a study of 91 patients with metastatic renal cell carcinoma (mRCC), nivolumab showed significant improvements in overall survival, with a median survival of 25.2 months for the highest dose (10 mg/kg) and not reached for treatment-naïve patients.

Nivolumab treatment led to substantial increases in tumor-associated lymphocytes and changes in chemokine levels, indicating its immunomodulatory effects, while no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. Choueiri, TK., Fishman, MN., Escudier, B., et al.[2022]

A 65-year-old man with advanced renal cell carcinoma achieved a remarkable reduction in metastasis after receiving nivolumab as the fifth systemic therapy, following treatment with angiogenesis inhibitors and interferon-α.

The patient experienced a pathological complete response, with no cancer cells found after adrenalectomy, and remains healthy 20 months post-surgery, highlighting the potential efficacy of nivolumab in advanced renal cell carcinoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma. Hagimoto, H., Kashima, S., Doi, K., et al.[2022]

Nivolumab, when combined with ipilimumab, significantly improves overall survival (OS) and progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC), based on a meta-analysis of three high-quality randomized controlled trials involving 2550 patients.

The treatment with nivolumab did not lead to an increase in adverse events, indicating a manageable safety profile for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nivolumab for Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. Zhang, S., Xu, X., Chen, J., et al.[2022]

In a study of 389 metastatic renal cell carcinoma patients with poor prognostic features, nivolumab demonstrated a disease control rate of 53% in those with brain metastasis, 45% in liver metastasis, and 47% in bone metastasis, indicating its efficacy in difficult-to-treat populations.

The safety profile of nivolumab remained consistent with previous studies, with no new safety concerns identified, suggesting it is a safe treatment option for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Negative prognostic factors and resulting clinical outcome in patients with metastatic renal cell carcinoma included in the Italian nivolumab-expanded access program. Bracarda, S., Galli, L., Maruzzo, M., et al.[2018]

Nivolumab, an immunotherapy drug, can cause life-threatening interstitial pneumonitis in patients on hemodialysis, as demonstrated in a case study of a 61-year-old man with metastatic renal cell carcinoma.

Prompt corticosteroid treatment was effective in alleviating the symptoms of pneumonitis, highlighting the need for careful monitoring and management when administering nivolumab to patients with compromised kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapidly progressing programmed cell death 1 inhibitor-related pneumonitis in a hemodialytic patient with metastatic renal cell carcinoma. Matsumura, Y., Iemura, Y., Fukui, S., et al.[2022]

A patient on hemodialysis with advanced clear-cell renal cell carcinoma successfully received combined immune checkpoint blockade therapy with nivolumab and ipilimumab, showing no significant immune-related adverse events.

This case supports the safety and efficacy of using nivolumab and ipilimumab in patients on hemodialysis, suggesting that renal function does not significantly impact the treatment's pharmacokinetics or safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. Kobayashi, Y., Arai, H., Honda, M.[2023]

In a real-world analysis of adverse events from two combination therapies for advanced renal cell carcinoma, cabozantinib (CAB) plus nivolumab (NIVO) showed higher incidence rates of seven types of toxicities compared to ipilimumab (IPI) plus NIVO.

Conversely, IPI + NIVO was associated with higher rates of three types of toxicities and had a greater incidence of serious adverse events, suggesting that both therapies have distinct safety profiles that can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. Blas, L., Shiota, M., Tsukahara, S., et al.[2023]

In a study of 35 patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab, 62.9% experienced immune-related adverse events, which were associated with significantly longer progression-free and overall survival rates.

The presence of immune-related adverse events, particularly skin reactions, was identified as an independent predictor of better clinical outcomes, suggesting that these events could serve as effective biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. Ueda, K., Suekane, S., Kurose, H., et al.[2022]

This case report describes the first known instance of minimal change disease with nephrotic syndrome linked to the PD-1 inhibitor Nivolumab, occurring in a 57-year-old man after one month of treatment for metastatic squamous cell carcinoma.

Despite treatment with corticosteroids and stopping Nivolumab, the patient's kidney function and nephrotic syndrome did not improve, highlighting the need for awareness of various kidney complications associated with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal change disease in a patient receiving checkpoint inhibition: Another possible manifestation of kidney autoimmunity? Vaughan, E., Connolly, E., Hui, M., et al.[2021]

Nivolumab combined with ipilimumab significantly improves overall survival in adult patients with intermediate/poor-risk advanced renal cell carcinoma compared to sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

In the study involving 1096 patients, the median overall survival was not reached for the nivolumab + ipilimumab group, while it was 25.95 months for the sunitinib group, highlighting the potential of this combination therapy for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. Ali, S., Camarero, J., Hennik, P., et al.[2021]

A 75-year-old male with metastatic renal cell carcinoma and inferior vena cava tumor thrombus showed significant regression of the tumor and pulmonary nodules after treatment with nivolumab and ipilimumab, indicating potential efficacy of this combination therapy.

Post-surgical histopathological analysis revealed no viable malignant cells, suggesting that nivolumab plus ipilimumab may effectively treat advanced cases of renal cell carcinoma, even in complex scenarios involving tumor thrombus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete response of metastatic renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus ipilimumab. Hayashida, M., Miura, Y., Noda, T., et al.[2022]

In a study of 41 patients with metastatic renal cell carcinoma treated with nivolumab and ipilimumab, deferred cytoreductive nephrectomy led to significant tumor shrinkage in both primary kidney and metastatic lesions, with 86% of patients showing at least 30% reduction.

Patients who underwent deferred nephrectomy had a higher overall survival rate (100% at 1 year) compared to those who had upfront nephrectomy (72.4%) or no nephrectomy (58.2%), suggesting a potential therapeutic benefit of this approach after immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Yoshino, M., Ishihara, H., Nemoto, Y., et al.[2022]

In a subgroup of 108 patients with advanced renal cell carcinoma (aRCC) who had not undergone nephrectomy, treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a significant survival advantage over sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

NIVO+IPI also resulted in a higher objective response rate (34% vs 15%) and greater tumor shrinkage (35% of patients achieving a ≥30% reduction in tumor size) compared to sunitinib, demonstrating its efficacy in this under-represented patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial. Albiges, L., Tannir, NM., Burotto, M., et al.[2023]

References

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

Checkpoint Inhibitor Combo Effective for RCC. [2019]

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

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma. [2022]

4. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nivolumab for Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Negative prognostic factors and resulting clinical outcome in patients with metastatic renal cell carcinoma included in the Italian nivolumab-expanded access program. [2018]

6. Australia pubmed.ncbi.nlm.nih.gov

Rapidly progressing programmed cell death 1 inhibitor-related pneumonitis in a hemodialytic patient with metastatic renal cell carcinoma. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. [2023]

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

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

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

Minimal change disease in a patient receiving checkpoint inhibition: Another possible manifestation of kidney autoimmunity? [2021]

11. England pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. [2021]

12. Australia pubmed.ncbi.nlm.nih.gov

Complete response of metastatic renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus ipilimumab. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

14. Switzerland pubmed.ncbi.nlm.nih.gov

First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial. [2023]