KCA-Funded Research Published in 2024
Several researchers who received funding from the Kidney Cancer Association published exciting new findings in 2024 based on their work. These papers and presentations are the important work of better understanding how kidney cancer works and uncovering new and more effective ways to treat it. Read on for a summary of these publications.
New kidney cancer-specific quality of life tool
Q&A: Dr. Cristiane Bergerot, Focus Award: Psychosocial recipient
Dr. Cristiane Bergerot of Grupo Oncoclinicas in Brazil developed a patient-centered health-related quality of life (HQROL) assessment tool tailored to metastatic renal cell carcinoma (mRCC) patients following a psychosocial-focused KCA research grant in 2021. Since then, along with inputs from kidney cancer patient advocates, Bergerot continued to refine the tool to ensure that patient-reported outcomes and critical patient concerns, often overlooked in research, can be integrated into care delivery. The 12-item questionnaire includes cancer-related, emotional, and physical categories addressing areas including energy and pain, depression, and physical activity. Bergerot plans to further validate the tool, which could replace existing HRQOL measures in kidney cancer-specific clinical circumstances.
Publication: Development of a patient-centered health-related quality of life (HRQOL) measure for metastatic renal cell carcinoma (mRCC): A three-phase study. Journal of Clinical Oncology, 42(4_suppl), 365-365 – January 2024
PIM1 kinase expression could be modulated with existing drugs.
Q&A: Dr. Sheldon Holder, KCA Trailblazer Award winner
Dr. Sheldon Holder of the Legorreta Cancer Center at Brown University received a 2022 KCA Trailblazer Award to examine the connection between the signaling molecule IL-6 and the PIM1 kinase which is involved in cancer-related cellular activity like cell proliferation and is present in higher quantities in renal cell carcinoma. Blocking IL-6 reduced PIM1 expression so, especially since multiple IL-6-specific drugs already exist, this could be an important pathway to target for treatment.
Publication: IL-6 and PIM1 expression in renal cell carcinoma. Journal of Clinical Oncology, 42(4_suppl), 470-470 – January 2024
Pathogenic Role of RNASET2 in Clear Cell RCC
Q & A: Dr. Brandon Manley, 2020 YIA recipient
KCA-funded investigator Dr. Brandon Manley of the Moffitt Cancer Center has uncovered the pathogenic roles of RNASET2 in clear cell renal cell carcinoma, the most common RCC subtype. This research identifies novel mechanisms underlying the disease, creating opportunities for innovative therapeutic approaches that could improve survival and overall patient outcomes.
Publication: Pathogenic Roles for RNASET2 in Clear Cell Renal Cell Carcinoma Laboratory Investigation, 104(5), 102041 – February 2024
Single-cell mtDNA dynamics in tumor research
Q and A: Dr. Ed Reznik with Dr. Ari Hakimi
Supported by a KCA Young Investigator Award in 2019, Dr. Ed Reznik of Memorial Sloan Kettering Cancer Center published a study in Nature Genetics exploring the co-regulation of nuclear and mitochondrial genomes in tumors at the single-cell level. This cutting-edge research provides a foundational understanding of tumor biology, paving the way for highly targeted therapies and potential breakthroughs in personalized medicine for kidney cancer patients.
Publication: Single-cell mtDNA dynamics in tumors is driven by coregulation of nuclear and mitochondrial genomes Nature Genetics, 56(5), 889-899 – May 2024
The association of fructose and the gut microbiome on cancer survival
Q&A: Dr. Brendon Guercio, Interdisciplinary RCC Focus Award winner
2023 Trailblazer Award recipient Dr. Brendan Guercio of the University of Rochester examined the relationship between dietary fructose and immune checkpoint blockade in kidney cancer and found no impact on progression-free survival in renal cell carcinoma patients. In contrast, urothelial carcinoma patients did experience shorter progression-free survival. This discrepancy suggests further study to better characterize cancer biology and how fructose as part of the gut microbiome could lead to potential beneficial dietary interventions.
Publication: Associations of dietary fructose with survival of patients (pts) with metastatic cancer of the urothelium (UC) and renal cell carcinoma (RCC) on immune checkpoint blockade (ICB). Journal of Clinical Oncology, 42(16_suppl), 4571-4571 – May 2024
Recent Blog Posts
Q&A: Dr. Angela Cappello, KCA Trailblazer Award winner
December 11, 2024
Angela Cappello, PhD, received a 2024 KCA Trailblazer Award for research on “Drugs resistance mechanisms guided by amino acids catabolism…
Our Top 10 Research Initiatives of 2024
This year, the Kidney Cancer Association made headway on multiple research initiatives across a range of focus areas. Here are…
December 3, 2024
Several researchers who received funding from the Kidney Cancer Association published exciting new findings in 2024 based on their work.…
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Clinical Trials to Treat Kidney (Renal Cell) Cancer
This phase III trial compares standard systemic treatment alone versus standard systemic treatment plus surgery to remove all or part of the affected kidney (cytoreductive nephrectomy) in treating patients with kidney cancer that has spread to other places in the body (metastatic). Standard systemic therapy for this type of cancer is immunotherapy-based combination therapy which may shrink the tumor and stimulate the immune system to attack the cancer. Systemic therapy is a type of treatment when drugs travel through the blood to cells all over the body. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cytoreductive nephrectomy is a surgical procedure to remove as many cancer cells from the kidney as possible. This study will help determine whether addition of surgery to standard of care systemic therapy is better than systemic therapy alone for the treatment of metastatic kidney cancer.
This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.
This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.
This phase II trial compares the effect of atezolizumab in combination with usual treatment with cabozantinib to cabozantinib alone in patients with papillary renal cell carcinoma that has spread to other places in the body (metastatic). Papillary renal cell carcinoma (PRCC) is a type of kidney cancer that forms in the lining of the tiny tubes in the kidney that return filtered substances that the body needs back to the blood and remove extra fluid and waste as urine. Most papillary tumors look like long, thin finger-like growths under a microscope. It is also called papillary kidney cancer or PRCC. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help body’s immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply and may also prevent the growth of new blood vessels that tumors need to grow. By these actions it may help slow or stop the spread of cancer cells. Combination therapy with atezolizumab and cabozantinib may shrink the cancer and allow a longer survival time in patients with metastatic renal cell carcinoma.
This phase III trial compares the effect of stereotactic ablative radiotherapy (SAbR) followed by standard of care systemic therapy, to standard of care systemic therapy alone, in patients with renal cell carcinoma or RCC (the most common type of kidney cancer) that has spread from where it first started (primary site) to a limited number of places in the body (metastatic). There are patients with metastatic RCC who have limited metastatic disease (oligometastatic). In patients with advanced oligometastatic disease, radiation therapy as a local treatment of metastatic lesions may be beneficial (without systemic therapy and associated toxicity and costs). Previous small-scale studies have demonstrated that SAbR alone can control oligometastatic RCC for some time, which may be comparable to the control afforded by systemic therapies. However, to confirm this finding, larger scale studies like this must be performed to check whether SAbR can become a standard option for such patients in the future. Radiotherapy uses high energy x-rays to kill cancer cells and shrink tumors. SAbR is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. SAbR may allow patients to live longer with better quality of life. SAbR may delay or possibly eliminate the need for systemic therapy and its more serious side effects. Giving SAbR prior to systemic therapy may kill the tumor cells more efficiently than the usual approach with systemic therapy alone.
This phase III trial compares the effectiveness of fractionated stereotactic radiosurgery (FSRS) to usual care stereotactic radiosurgery (SRS) in treating patients with cancer that has spread from where it first started to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. FSRS delivers a high dose of radiation to the tumor over 3 treatments. SRS is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. FSRS may be more effective compared to SRS in treating patients with cancer that has spread to the brain.
This phase II trial studies whether adding radium-223 dichloride to the usual treatment, cabozantinib, improves outcomes in patients with renal cell cancer that has spread to the bone. Radioactive drugs such as radium-223 dichloride may directly target radiation to cancer cells and minimize harm to normal cells. Cabozantinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving radium-223 dichloride and cabozantinib may help lessen the pain and symptoms from renal cell cancer that has spread to the bone, compared to cabozantinib alone.
This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, PK, preliminary antitumor activity, and effect of biomarkers of XL092 administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) in subjects with advanced solid tumors. In the Expansion Stage, the safety and efficacy of XL092 as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.
This is a Phase 1b, open-label, multicenter, safety, tolerability and efficacy study of HC-7366 in combination with belzutifan (WELIREG™). This is a multipart study that consists of a HC-7366 monotherapy cohort, a combination dose escalation, and a combination dose expansion. Approximately 80 patients will be enrolled in this study (up to 20 patients will be enrolled into the HC-7366 monotherapy cohort, up to 30 patients into the combination dose escalation, and up to 30 patients into the combination dose expansion). The primary purpose of this study is to determine the maximum tolerated dose of HC-7366 in combination with belzutifan in patients with locally advanced (inoperable) or metastatic RCC with predominantly clear cell histology, irrespective of VHL gene mutation status.
This is a first-in-human, phase 1a/1b, multicenter, open-label, dose escalation study of STK-012 as monotherapy and in combination therapy in patients with selected advanced solid tumors.
This phase II trial tests how well stereotactic body radiation therapy (SBRT) works in treating renal cell carcinoma that has spread from where it first started (primary site) to other places in the body (metastatic) in patients who have developed disease progression at a limited number of sites (up to 5) (oligoprogression) after treatment with immune checkpoint inhibitor drugs. Radiation therapy uses high energy x-rays or particles to kill tumor cells and shrink tumors. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Adding SBRT and continuing standard immune checkpoint inhibitor treatment may prolong survival without progression of metastatic renal cell cancer compared to standard of care which will include second line systemic therapy.
This phase II trial studies the effects of combination therapy with bevacizumab, erlotinib, and atezolizumab in treating patients with hereditary leiomyomatosis and kidney cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Bevacizumab is in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumors. This may slow the growth and spread of tumors. Erlotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Combination therapy with bevacizumab, erlotinib, and atezolizumab may stabilize or shrink advanced hereditary leiomyomatosis and kidney cancer.
This study is about TAK-500, given either alone or with pembrolizumab, in adults with select locally advanced or metastatic solid tumors. The aims of the study are: - to assess the safety profile of TAK-500 when given alone and when given with pembrolizumab. - to assess the anti-tumor effects of TAK-500, when given alone and when given with pembrolizumab, in adults with locally advanced or metastatic solid tumors. Participants may receive TAK-500 for up to 1 year. Participants may continue with their treatment if they have continuing benefit and if this is approved by their study doctor. Participants who are receiving TAK-500 either alone or with pembrolizumab will continue with their treatment until their disease progresses or until they or their study doctor decide they should stop this treatment.
This is a First-in-Human Phase IA/IB/II open label dose escalation study of intravenous (IV) administration of ONC-392, a humanized anti-CTLA4 IgG1 monoclonal antibody, as single agent and in combination with pembrolizumab in participants with advanced or metastatic solid tumors and non-small cell lung cancers.
The study will assess the safety, PK, PD, and preliminary efficacy of ABBV-CLS-484 as monotherapy and in combination with a PD-1 targeting agent or with a or a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-484 as monotherapy and in combination. The study will be conducted in three parts. Part 1 Monotherapy Dose Escalation, Part 2 Combination Dose Escalation and Part 3 Dose Expansion (Monotherapy and Combination therapy). Part 1, ABBV-CLS-484 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-484 will be administered at escalating dose levels in combination with a PD-1 targeting agent or with a VEGFR TKI to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-484 will be administered alone as a monotherapy at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC). ABBV-CLS-484 will also be administered at the determined recommended dose in combination with a PD-1 targeting or with a VEGFR TKI agent in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.
This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and in combination, in adult patients with advanced solid tumors.
This phase II trial tests how well botensilimab and balstilimab versus nivolumab and ipilimumab works to treat patients with clear cell renal cell carcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Immunotherapy with monoclonal antibodies, such as botensilimab, balstilimab, nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. They work by binding to a substance in the body, including tumor cells, to help the body's immune system kill the tumor cells. Combination nivolumab and ipilimumab is the standard frontline treatment for patients with advanced clear cell carcinoma; however, even with good initial response, most patients still progress on this therapy. Giving botensilimab and balstilimab may be more safe and effective than standard treatment for patients with advanced clear cell renal cell carcinoma.
The primary objective of the study is to compare V940 plus pembrolizumab to placebo plus pembrolizumab in participants with renal cell carcinoma (RCC) with respect to disease-free survival (DFS) as assessed by the investigator. The primary hypothesis is that V940 plus pembrolizumab is superior to placebo plus pembrolizumab with respect to DFS.
This is a multi-center, open-label phase 1/2 trial evaluating the safety and efficacy of AB-2100 cell product. The study may enroll approximately 60 patients in phase 1 and approximately 70 patients in phase 2.
The purpose of this study is to assess the safety and tolerability of XmAb®819 administered intravenous (IV) or subcutaneous (SC) in subjects with relapsed or refractory clear cell renal cell carcinoma and to identify the minimum safe and biologically active dose and the recommended dose (RD).
The purpose of this study is to evaluate the safety and tolerability of: - casdatifan when taken alone in participants with advanced solid tumor malignancies and clear cell renal cell carcinoma (ccRCC) during the dose escalation stage; and - casdatifan monotherapy and casdatifan in combination with cabozantinib in participants with ccRCC in the dose expansion stage
This is a Phase 1/1b, open-label, first-in-human, dose-escalation and expansion study of CHS-388, a monoclonal antibody that targets IL-27, as a monotherapy and in combination in patients with solid tumors.
This study is a first-in-human (FIH), Phase 1/1b, open-label, multicenter dose escalation and dose expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of JANX008 in adult subjects with advanced or metastatic carcinoma expressing EGFR.
This phase II trial studies the side effects and best dose of 177Lu-girentuximab when given together with nivolumab in treating patients with kidney cancer. 177Lu-girentuximab is a type of treatment called radioimmunotherapy, and it includes an antibody (similar to antibodies made by the immune system to help fight infections) and a radioactive particle that gives off a small amount of radiation. 177Lu-girentuximab targets the protein CAIX, which is on the cancer cells of about 90% of people who have kidney cancer. The antibody part of the therapy (girentuximab) attaches to the CAIX protein and delivers the radioactive particle (lutetium-177) directly to the cancer cells. The radioactive particle gives off radiation to kill the cancer cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab in combination with 177Lu-girentuximab may kill more tumor cells in patients with renal cell carcinoma.
This is a Phase 1/2, open-label, non-randomized, 4-part trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda®). KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
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