Canakinumab + Spartalizumab for Renal Cell Carcinoma

(SPARC-1 Trial)

Not currently recruiting at 1 trial location

Overseen By Monica Hounsell

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Columbia University

Must not be taking: Steroids, Immunosuppressants, Live vaccines, others

Disqualifiers: Metastases, Autoimmune disease, Infections, others

Stay on Your Current Meds You can continue your current medications while participating

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and potential benefits of combining two drugs, canakinumab (an anti-inflammatory medication) and spartalizumab (an immunotherapy drug), for treating renal cell carcinoma (a type of kidney cancer). Researchers aim to observe the immune system's response to this combination and determine if it can shrink tumors before surgery. Individuals with confirmed or suspected kidney cancer who plan to undergo surgery might be suitable candidates for this study. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this novel combination therapy.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic chronic steroid therapy or any immunosuppressive therapy 7 days before the first dose of the study treatment. Topical, inhaled, nasal, and ophthalmic steroids are allowed.

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

Research has shown that using canakinumab and spartalizumab together has been studied for safety in treating kidney cancer. Past patients demonstrated that these drugs can be used together without serious side effects. Some studies found that most people handled the combination well.

Most side effects were mild or moderate, such as fatigue, fever, or skin reactions. Serious side effects were rare. Since this trial is in an early stage, it primarily aims to confirm the combination's safety for people.

In other studies, these drugs have been used to treat different types of cancer, providing more information about their safety. While researchers continue to study the combination, current data suggest it is generally safe to use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Canakinumab and Spartalizumab for renal cell carcinoma because these treatments offer a fresh approach compared to traditional options like surgery and targeted therapies. Canakinumab is an antibody that targets interleukin-1β, a molecule involved in inflammation, which might help in reducing tumor-promoting inflammation. Spartalizumab is a type of immunotherapy known as a PD-1 inhibitor, which works by boosting the body's immune response to fight cancer cells more effectively. Together, these treatments aim to enhance the immune system's ability to combat cancer, potentially leading to more effective outcomes for patients with renal cell carcinoma.

What evidence suggests that canakinumab and spartalizumab might be effective for renal cell carcinoma?

Research has shown that using canakinumab and spartalizumab together might help treat renal cell carcinoma, a type of kidney cancer. In this trial, participants will receive both canakinumab and spartalizumab as part of the study treatment. Spartalizumab belongs to a group of treatments called immune checkpoint blockades, which have shown promise in helping patients with this cancer. In past studies, patients who received these immune therapies experienced tumor shrinkage before surgery. The goal of combining these treatments is to strengthen the body's immune response against cancer cells. Although still in early stages, these treatments might reduce tumor size, making surgeries more effective. ^{1 2 3 6 7}

Who Is on the Research Team?

Karie Runcie

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults with localized clear cell Renal Cell Carcinoma (RCC) who are scheduled for kidney surgery. They must be willing to use barrier contraception, have no history of severe infections or autoimmune diseases, and not have received prior RCC treatments or immune-modulating drugs. HIV-positive patients can join if they're healthy with controlled viral loads.

Inclusion Criteria

I agree to use barrier contraception until 120 days after my surgery.

Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements

I am fully active or have some restrictions but can still care for myself.

Exclusion Criteria

I have not received any live vaccines in the last 4 weeks.

I have had a bone marrow or organ transplant from another person.

I do not have any severe infections or heart, lung, blood, or mental health conditions that would make me unsuitable for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive canakinumab and spartalizumab every 4 weeks for 2 doses prior to radical nephrectomy

8 weeks

2 visits (in-person)

Surgery

Participants undergo radical nephrectomy approximately 14 days after the last dose of treatment

2 weeks

Follow-up

Participants are monitored for adverse events 30 and 90 days after surgery, with repeat labs every 3 months and standard surveillance imaging

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Canakinumab
• Spartalizumab

Trial Overview The study tests the safety and effectiveness of combining two drugs, Spartalizumab and Canakinumab, before kidney surgery in RCC patients. It aims to see how well this combination works in shrinking tumors and enhancing the body's immune response against cancer.

How Is the Trial Designed?

Group I: Spartalizumab and Canakinumab Experimental Treatment 2 Interventions

Subjects with renal cell carcinoma will receive study treatment Q4 weeks x 2 doses prior to radical nephrectomy.

Canakinumab is already approved in European Union, United States for the following indications:

Approved in European Union as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Approved in United States as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Matthew Dallos

Lead Sponsor

Trials

4

Recruited

140+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Published Research Related to This Trial

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]

In a phase 1/2 study involving 58 patients with advanced solid tumors, spartalizumab was found to be well tolerated with no dose-limiting toxicities, indicating a favorable safety profile for this PD-1 blocking antibody.

Although spartalizumab showed limited clinical activity with a response rate of only 3.4% in this heavily pretreated population, there was evidence of immune activation, as indicated by increased CD8+ lymphocyte infiltration in tumor biopsies from patients who experienced clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti-PD-1 antibody, in patients with advanced solid tumors. Naing, A., Gainor, JF., Gelderblom, H., et al.[2023]

In a phase I study involving 18 patients with advanced cancers, spartalizumab was found to be safe at doses up to 10 mg/kg every two weeks, with no dose-limiting toxicities reported.

The study showed preliminary antitumor activity, with partial responses observed in 11% of patients, indicating potential effectiveness in treating certain types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of the antiprogrammed cell death-1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies. Minami, H., Doi, T., Toyoda, M., et al.[2021]

In a phase I/II study involving 219 patients with advanced solid tumors, the combination of sabatolimab and spartalizumab was well tolerated, with fatigue being the most common treatment-related side effect.

While no responses were observed with sabatolimab alone, the combination treatment showed preliminary antitumor activity, with 5 patients achieving partial responses in various cancers, suggesting potential efficacy in specific populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors. Curigliano, G., Gelderblom, H., Mach, N., et al.[2023]

In a study of 53 patients with metastatic non-clear cell renal cell carcinoma (nccRCC) and sarcomatoid renal cell carcinoma (sRCC), sunitinib showed a significantly better overall survival (OS) compared to pazopanib, with median OS of 30.4 months versus 8.7 months, respectively.

The analysis indicated that pazopanib was associated with inferior progression-free survival (PFS) as well, with a median PFS of 4.9 months compared to 6.6 months for sunitinib, suggesting that sunitinib may be the more effective first-line treatment for these types of renal cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence on first-line treatment for metastatic renal cell carcinoma with non-clear cell and sarcomatoid histologies: are sunitinib and pazopanib interchangeable? Bonadioa, RC., Velho, PI., Marta, GN., et al.[2022]

Recent advances in understanding renal cell cancer (RCC) have led to the development of six new targeted therapies that significantly improve progression-free survival (PFS) compared to previous treatments, with a consistent doubling of PFS observed in clinical trials.

These new drugs, including sorafenib and sunitinib, are generally well tolerated and provide clinical benefits to over 70% of patients, although their unique side effects require careful management to maintain quality of life during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy in renal cancer. Dorff, TB., Goldkorn, A., Quinn, DI.[2021]

AMG 172, an anti-CD27L antibody-drug conjugate, was found to have a maximum tolerated dose of 1.6 mg/kg, with common side effects including thrombocytopenia and liver injury, leading to treatment discontinuation in some cases.

While AMG 172 demonstrated a favorable pharmacokinetic profile, only 5.4% of patients experienced a partial response, indicating limited antitumor activity in patients with relapsed/refractory clear cell renal cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human study to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of the anti-CD27L antibody-drug conjugate AMG 172 in patients with relapsed/refractory renal cell carcinoma. Massard, C., Soria, JC., Krauss, J., et al.[2020]

In the phase III JAVELIN Renal 101 trial, avelumab plus axitinib demonstrated significantly improved progression-free survival (PFS) of 13.9 months compared to 8.5 months for sunitinib, indicating better efficacy in treating advanced renal cell carcinoma.

The overall survival (OS) trend also favored avelumab plus axitinib, with a hazard ratio of 0.79 compared to sunitinib, although the data is still immature and requires further follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma. Haanen, JBAG., Larkin, J., Choueiri, TK., et al.[2023]

Axitinib is a newly approved targeted therapy for advanced renal cell cancer that shows greater potency in inhibiting VEGFR1-3 compared to earlier treatments, significantly improving patient outcomes based on phase II and III clinical trials.

The drug has a manageable toxicity profile and is unique in allowing for dose titration, making it a recommended standard treatment for patients who have previously undergone antiangiogenic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib: a review of its safety and efficacy in the treatment of adults with advanced renal cell carcinoma. Gross-Goupil, M., François, L., Quivy, A., et al.[2021]

In a phase I trial involving 25 patients, including 7 with metastatic renal cell carcinoma (mRCC), the combination of pazopanib and bevacizumab showed a manageable toxicity profile, although significant dose-limiting toxicities (DLTs) were observed, particularly at higher doses.

Despite achieving a partial response in 22% of patients, the combination therapy's toxicity, including a notable incidence of grade 3 microangiopathic hemolytic anemia, raises concerns about its further development for treating advanced tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of pazopanib combined with bevacizumab in patients with metastatic renal cell carcinoma or other advanced tumors. Négrier, S., Pérol, D., Bahleda, R., et al.[2021]

In the IMmotion150 study involving 305 patients with metastatic renal cell carcinoma, atezolizumab combined with bevacizumab did not show a significant improvement in progression-free survival (PFS) compared to sunitinib, with a hazard ratio of 1.0, indicating similar effectiveness.

Exploratory analyses revealed that certain molecular profiles, such as angiogenesis and immune response signatures, may help predict treatment outcomes, suggesting that targeting VEGF could enhance the effectiveness of immunotherapy in overcoming resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. McDermott, DF., Huseni, MA., Atkins, MB., et al.[2022]

Recent advances in understanding the molecular mechanisms of renal cell carcinoma have led to the development of targeted therapies, including VEGF inhibitors like bevacizumab and tyrosine kinase inhibitors such as sunitinib and pazopanib, which have shown efficacy in Phase III trials.

The review also highlights the importance of optimizing treatment management strategies, including determining the appropriate timing for starting and stopping therapy, as well as exploring alternative dosing schedules for sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical management of metastatic kidney cancer: the role of new molecular drugs. Vitale, MG., Cartenì, G.[2021]

Advanced renal cell carcinoma is resistant to many traditional therapies, but new immunotherapeutic approaches, including monoclonal antibodies and kinase inhibitors, are being explored, showing good tolerance and stable disease rates.

Two recently approved agents, a kinase inhibitor and an mTOR inhibitor, are now recommended as first-line treatments, while sorafenib is suggested for second-line therapy, highlighting the need for further research on their combinations and sequential use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current immunotherapeutic strategies in renal cell carcinoma. Amato, RJ.[2009]

In a phase III trial involving 649 patients with metastatic renal cell carcinoma, the combination of bevacizumab and interferon alfa significantly improved progression-free survival (10.2 months vs. 5.4 months) compared to interferon alfa alone, indicating enhanced efficacy of the combination treatment.

The safety profile of the combination treatment was acceptable, with only a small percentage of deaths (2%) related to bevacizumab, and the most common severe side effects were fatigue and asthenia, suggesting that the treatment is relatively safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Escudier, B., Pluzanska, A., Koralewski, P., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04028245?term=Spartalizumab&rank=5

A Study of Combination Spartalizumab and Canakinumab in ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11763366/

A Review of Neoadjuvant Therapy for Localized and ... This review will look at the available data on the use of immunotherapy and targeted therapy for patients with localized kidney cancer.

3. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2021.39.6_suppl.TPS373

The SPARC-1 trial: A phase I study of neoadjuvant ... Background: Immune checkpoint blockade has significantly improved outcomes for patients with renal cell carcinoma (RCC) in the metastatic ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-01069

Neoadjuvant Spartalizumab and Canakinumab for the ... This pilot phase Ib trial studies the side effects and how well spartalizumab and canakinumab work in treating patients with kidney cancer that that has not ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124002116

Neoadjuvant and Adjuvant Immune-based Approach for ... Adjuvant immunotherapy is a new standard of care in RCC. Both neoadjuvant and adjuvant immunotherapy strategies have potential advantages and disadvantages.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7783360/

Complete Pathologic Responses With Immunotherapy in ... Introduction. Immunotherapy and immunotherapy-based combinations have revolutionized the treatment of advanced renal cell carcinoma (RCC).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04028245

A Study of Combination Spartalizumab and Canakinumab ... This study intends to confirm the safety and feasibility of canakinumab and spartalizumab (PDR-001) administered using a standard dose / schedule in the neo- ...