Canakinumab + Spartalizumab for Renal Cell Carcinoma
(SPARC-1 Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byMatthew Dallos, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Columbia University
Must not be taking: Steroids, Immunosuppressants, Live vaccines, others
Disqualifiers: Metastases, Autoimmune disease, Infections, others
Stay on Your Current Meds
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?Primary Objective:
* To confirm the safety and feasibility of canakinumab and spartalizumab (PDR-001) administered using a standard dose / schedule in the neo-adjuvant setting in renal cell carcinoma
Secondary Objectives:
* To assess the immune response to combination canakinumab and spartalizumab
* To assess anti-tumor activity as measured by pathologic downstaging
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.
What data supports the idea that Canakinumab + Spartalizumab for Renal Cell Carcinoma is an effective drug?
The available research does not provide specific data on the effectiveness of Canakinumab + Spartalizumab for Renal Cell Carcinoma. Instead, it discusses other treatments like atezolizumab combined with bevacizumab, and various targeted therapies such as sorafenib, sunitinib, and temsirolimus, which have shown benefits in terms of disease stability and progression-free survival. These treatments have been tested in clinical trials and have demonstrated improvements over previous standard therapies. However, there is no direct comparison or data available for Canakinumab + Spartalizumab in the provided information.
12345What safety data exists for Canakinumab and Spartalizumab in treating renal cell carcinoma?
The safety data for Spartalizumab, an anti-PD-1 antibody, has been evaluated in multiple studies. In a phase 1 study involving Japanese patients with advanced malignancies, Spartalizumab was administered at doses up to 10 mg/kg every 2 weeks. No dose-limiting toxicities were reported, and the safety profile was consistent with other approved anti-PD-1 antibodies. Common adverse events included maculopapular rash, malaise, and increased blood alkaline phosphatase. Another study evaluated Sabatolimab (an anti-TIM-3 antibody) alone and in combination with Spartalizumab, indicating that the combination was assessed for safety in advanced solid tumors. However, specific safety data for Canakinumab in combination with Spartalizumab for renal cell carcinoma is not detailed in the provided research.
678910Is the drug Canakinumab, Spartalizumab a promising treatment for kidney cancer?
The trial titled 'Canakinumab + Spartalizumab for Renal Cell Carcinoma' suggests that this combination could be a promising treatment for kidney cancer. While the specific articles provided do not directly discuss Canakinumab and Spartalizumab, they highlight the importance of exploring new treatments for renal cell carcinoma, a type of kidney cancer. This trial represents an effort to find effective therapies for this disease.
911121314Eligibility Criteria
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 am 18 years old or older.
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
+8 more
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.
+15 more
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Spartalizumab and CanakinumabExperimental Treatment2 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Columbia University Medical CenterNew York, NY
Columbia University Irving Medical CenterNew York, NY
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Who Is Running the Clinical Trial?
Columbia UniversityLead Sponsor
Matthew DallosLead Sponsor
NovartisIndustry Sponsor
References
Clinical management of metastatic kidney cancer: the role of new molecular drugs. [2021]Over the last few years, the most recent advances of the molecular mechanisms involved in renal cell carcinoma have led to the use of new drugs targeting VEGF, such as bevacizumab plus interferon, sorafenib, sunitinib, pazopanib, and axitinib, or the mTOR, such as temsirolimus and everolimus. The purpose of this review is to analyze the results of Phase III trial with these targeted agents, and on the management of the treatment and, in particular, when to start and to stop therapy and the use of alternative schedule of sunitinib. Recent developments in immunotherapy are also discussed.
Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. [2022]We describe results from IMmotion150, a randomized phase 2 study of atezolizumab (anti-PD-L1) alone or combined with bevacizumab (anti-VEGF) versus sunitinib in 305 patients with treatment-naive metastatic renal cell carcinoma. Co-primary endpoints were progression-free survival (PFS) in intent-to-treat and PD-L1+ populations. Intent-to-treat PFS hazard ratios for atezolizumab + bevacizumab or atezolizumab monotherapy versus sunitinib were 1.0 (95% confidence interval (CI), 0.69-1.45) and 1.19 (95% CI, 0.82-1.71), respectively; PD-L1+ PFS hazard ratios were 0.64 (95% CI, 0.38-1.08) and 1.03 (95% CI, 0.63-1.67), respectively. Exploratory biomarker analyses indicated that tumor mutation and neoantigen burden were not associated with PFS. Angiogenesis, T-effector/IFN-γ response, and myeloid inflammatory gene expression signatures were strongly and differentially associated with PFS within and across the treatments. These molecular profiles suggest that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade.
Targeted therapy in renal cancer. [2021]Renal cell cancer (RCC) has an increasing incidence internationally and is a disease for which there have been limited therapeutic options until recently. The last decade has seen a vastly improved understanding of the biological and clinical factors that predict the outcome of this disease. We now understand some of the different molecular underpinnings of renal clear cell carcinoma by mutation or silencing of the von Hippel Lindau (VHL) gene and subsequent deregulated proliferation and angiogenesis. Survival in advanced disease is predicted by factors (performance status, anemia, hypercalcemia, and serum lactate dehydrogenase, time from diagnosis to recurrence) incorporated into the Memorial Sloan Kettering Cancer Center (MSKCC) criteria (also referred to as 'Motzer' criteria). These criteria allow classification of patients with RCC into good, intermediate and poor risk categories with median overall survivals of 22 months, 12 months and 5.4 months, respectively. Predicated upon these advances, six new targeted drugs (sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab and pazopanib) have been tested in well-designed phase III trials, selected or stratified for MSKCC risk criteria, with positive results. All of these new drugs act at least in part through vascular endothelial growth factor (VEGF) mediated pathways with other potential therapeutic impact on platelet-derived growth factor (PDGF), raf kinase and mammalian target of rapamycin (mTOR) pathways. Importantly, data from each of these trials show a consistent doubling of progression-free survival (PFS) over prior standard of care treatments. In addition, sorafenib, sunitinib and temsirolimus, have demonstrated significant overall survival (OS) benefits as well; further follow-up is required to determine whether the disease control exhibited by everolimus and pazopanib will translate into a survival advantage. These drugs are generally well tolerated, as demonstrated by quality-of-life improvement in clinical trials, and result in clinical benefit for in excess of 70% of patients treated. They have challenged the traditional outcomes of clinical trial design by achieving their benefits with relatively few radiographic responses, but high rates of disease stability. The unique side-effect profile coupled with the chronicity of therapy requires increased vigilance to maximize exposure to the drugs while maintaining quality of life and minimizing toxicity. This review focuses on the background, clinical development and practical use of these new drugs in RCC.
Current immunotherapeutic strategies in renal cell carcinoma. [2009]Advanced renal cell carcinoma remains resistant to drug-, hormone-, and cytokine-based therapies. Promising new immunotherapeutic approaches include monoclonal antibodies, kinase inhibitors, mammalian target of rapamycin inhibition, dendritic cell, and tumor antigen vaccines. Most of these approaches have yet to produce clinical responses significantly superior to those of previous standard therapies, although most are well tolerated and elicit relatively high rates of stable disease. Two recently approved agents, a kinase inhibitor and a mTOR inhibitor, are recommended for use as first-line therapies against renal cell carcinoma. An additional approved tyrosine kinase inhibitor, sorafenib, is recommended as second-line therapy. More clinical research on these agents and their use in combination, especially sequentially, is warranted.
Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. [2022]Vascular endothelial growth factor (VEGF) inhibition is a valid therapeutic approach in renal cell carcinoma. Therefore, an investigation of the combination treatment of the humanised anti-VEGF monoclonal antibody bevacizumab with interferon alfa was warranted.
A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti-PD-1 antibody, in patients with advanced solid tumors. [2023]Spartalizumab is a humanized IgG4κ monoclonal antibody that binds programmed death-1 (PD-1) and blocks its interaction with PD-L1 and PD-L2. This phase 1/2 study was designed to assess the safety, pharmacokinetics, and preliminary efficacy of spartalizumab in patients with advanced or metastatic solid tumors.
Phase I study of the antiprogrammed cell death-1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies. [2021]Spartalizumab is a humanized IgG4/κ mAb directed against human programmed cell death-1 (PD-1). In this phase I study, we investigated safety, pharmacokinetics, preliminary antitumor activity, and toxicity of spartalizumab in patients with advanced malignancies. Patients (n = 18) with a range of tumor types received spartalizumab i.v. at doses of 1, 3, and 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or discontinuation at the discretion of the investigator or patient. Most patients (61%) had received five or more prior lines of therapy. No dose-limiting toxicities were reported and, hence, the maximum tolerated dose was 10 mg/kg or more. Pharmacokinetics in Japanese patients aligned with those reported in a global dose-escalation study. The safety profile was consistent with other approved anti-PD-1 mAbs; the most common drug-related adverse events were maculopapular rash (22%), followed by malaise and increased blood alkaline phosphatase (11% each). Partial responses were reported in two patients (11%), one with transitional cell carcinoma and the other with hepatocellular carcinoma. In conclusion, this study confirmed the safety of spartalizumab given at a dose of up to 10 mg/kg every 2 weeks in Japanese patients with cancers.
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. [2023]Sabatolimab (MBG453) and spartalizumab are mAbs that bind T-cell immunoglobulin domain and mucin domain-3 (TIM-3) and programmed death-1 (PD-1), respectively. This phase I/II study evaluated the safety and efficacy of sabatolimab, with or without spartalizumab, in patients with advanced solid tumors.
Axitinib: a review of its safety and efficacy in the treatment of adults with advanced renal cell carcinoma. [2021]Over the last seven years, seven targeted agents have been approved in the treatment of advanced or metastatic renal cell cancer, changing the therapeutic approach and prognosis of the disease dramatically. The latest agent with demonstrated efficacy is axitinib (Inlyta(®)). This new generation of tyrosine kinase agent differs from previously existing agents by its greater activity potency of inhibition of vascular endothelial growth factor-receptor (VEGFR1-3). This efficacy has been tested in phase II and III clinical trials. Axitinib is the only targeted agent that benefits from recommended titration, with intra-patient dose escalation. The toxicity profile of the drug is tolerable. This paper reviews the mechanism of action of axitinib, its metabolism, and its pharmacokinetic profile. Clinical data of efficacy and safety is also detailed. The agent has been integrated in the international therapeutic guidelines, as a standard in treatment of renal cell cancer patients, previously treated through antiangiogenic therapy.
Phase I dose-escalation study of pazopanib combined with bevacizumab in patients with metastatic renal cell carcinoma or other advanced tumors. [2021]Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors.
Real-world evidence on first-line treatment for metastatic renal cell carcinoma with non-clear cell and sarcomatoid histologies: are sunitinib and pazopanib interchangeable? [2022]Non-clear cell renal cell carcinoma (nccRCC) and sarcomatoid renal cell carcinoma (sRCC) are underrepresented in clinical trials. Treatment approaches are frequently extrapolated from data of clear cell renal cell carcinoma, in which pazopanib is non-inferior to sunitinib. We aim to compare the effectiveness of first-line sunitinib and pazopanib for nccRCC and sRCC.
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. [2020]This study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of the anti-CD27L antibody-drug conjugate AMG 172 in patients with relapsed/refractory clear cell renal cell carcinoma (ccRCC).
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. [2022]The objective was to determine the safety and clinical activity of atezolizumab (MPDL3280A), a humanized programmed death-ligand 1 (PD-L1) antibody, in renal cell carcinoma (RCC). Exploratory biomarkers were analyzed and associated with outcomes.
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. [2023]We report updated data for avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma from the third interim analysis of the phase III JAVELIN Renal 101 trial.