Kidney Cancer Trials

This study will compare the effectiveness and safety of two doses of belzutifan (a type of targeted therapy) in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that the higher dose of belzutifan is superior to the standard dose in terms of objective response rate (ORR). This study has 2 arms: specific doses will be provided by your treating physician Arm A: Dose A (standard dose) Participants receive Dose A (standard dose) of belzutifan by oral administration (by mouth or po), once a day, until disease progression or discontinuation. Arm B: Dose B (higher dose) Participants receive Dose B (higher dose) of belzutifan by oral administration, one daily, until disease progression or discontinuation.

This phase III trial compares the usual treatment (treatment with ipilimumab and nivolumab followed by nivolumab alone) to treatment with ipilimumab and nivolumab, followed by nivolumab with cabozantinib in patients with untreated renal cell carcinoma that has spread to other parts of the body. The addition of cabozantinib to the usual treatment may make it work better. Immunotherapy, such as nivolumab (Opdivo) and ipilimumab (Yervoy), may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Targeted therapy, such as cabozantinib, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known how well the combination of cabozantinib and nivolumab after initial treatment with ipilimumab and nivolumab works in treating patients with renal cell cancer that has spread to other parts of the body. This study has 2 arms: Arm A: Nivolumab INDUCTION: Patients receive nivolumab intravenously (IV) in clinic over 30 or 60 minutes PLUS ipilimumab IV over 60 minutes on day 1 of every 21 day cycle, for up to 4 cycles. TREATMENT: Patients receive nivolumab IV over 30 or 60 minutes on day 1 of every 28 day cycle. Arm B: Nivolumab + Cabozantinib INDUCTION: Patients receive nivolumab intravenously (IV) in clinic over 30 or 60 minutes PLUS ipilimumab IV over 60 minutes on day 1 of every 21 day cycle, for up to 4 cycles. TREATMENT: Patients receive nivolumab IV over 30 or 60 minutes on day 1 of every 28 day cycle PLUS cabozantinib orally (by mouth or PO) daily on days 1-28.

This is a multicenter Phase 1b, open-label study to assess safety, tolerability, and preliminary effectiveness of cabozantinib (Cabometyx, a type of targeted therapy) taken in combination with atezolizumab (Tecentriq, a type of immunotherapy) in subjects with multiple tumor types, including advanced urothelial carcinoma (UC) (including bladder, renal pelvis, ureter, urethra), and castration-resistant prostate cancer (CRPC). The study consists of two stages: in the Dose Escalation Stage, an appropriate recommended cabozantinib dose for combination with standard dosing regimen of atezolizumab will be established; in the Expansion Stage, tumor-specific cohorts will be enrolled in order to further evaluate the safety and effectiveness of the combination treatment in these tumor types. Dose escalation: Subjects will be enrolled in cohorts of 3-6 subjects for evaluation of cabozantinib tablet dose of either 20 mg, 40 mg, and 60 mg taken orally (PO) once daily in combination with standard dosing regimen of atezolizumab (1200 mg given by intravenous infusion once every 3 weeks). Expansion: Atezolizumab 1200 mg given by intravenous infusion once every 3 weeks will be given in combination with cabozantinib administered orally daily at the determined recommended dose from the Dose Escalation Stage.

The purpose of this study is to evaluate safety, tolerability, pharmacokinetics (how a drug moves through your body), immunogenicity (how a drug stimulates your immune system), and antitumor activity of MEDI5752 (a type of immunotherapy) in combination with axitinib (Inlyta, a type of targeted therapy) .in subjects with advanced renal cell carcinoma. All subjects will receive treatment with MEDI5752 in combination with axitinib – specific doses and dosing schedule will be provided by your treatment team.

This study will compare the efficacy and safety of belzutifan (a type of targeted therapy) plus lenvatinib (Lenvima, a type of targeted therapy) versus cabozantinib (Cabometyx, a type of targeted therapy) in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that belzutifan plus lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival. This study has 2 treatment arms: Arm A: Belzutifan + Lenvatinib Belzutifan 120 mg and lenvatinib 20 mg orally (PO) once a day (QD). Arm B: Cabozantinib Cabozantinib 60 mg orally once a day

This is a Phase I/II, open-label, multi-center study of axitinib (Inlyta, a type of targeted therapy) in combination with nivolumab (Opdivo, a type of immunotherapy) in patients with previously treated and untreated advanced renal cell carcinoma (RCC). This clinical study will be composed of a dose finding phase (Phase I) and two parallel dose expansion phases (Phase II). The dose finding phase will assess the safety of the combination and establish a recommended phase II dose in patients with advanced RCC who have received prior systemic therapy for metastatic disease. Phase II will evaluate the effectiveness of the combination in two parallel expansion cohorts in both previously treated and treatment naïve patients. All patients in all phases of this study will receive both drugs, at various doses. Axitinib is taken orally (by mouth) twice daily, although dose and dosing schedule may vary. Nivolumab is given intravenously (IV), dose and dosing schedule may vary.

This is a phase II trial of nivolumab (Opdivo, an immunotherapy) in treatment-naïve patients with clear cell renal cancer. Nivolumab has been shown to have anti-tumor activity in renal cell patients. It is hypothesized that patients may still respond (have anti-tumor activity) by giving ipilimumab with nivolumab when the patient is no longer responding to nivolumab alone.

In Part A, nivolumab 240 mg will be given intravenously (IV) in clinic once every two weeks for six doses. Patients who remain on study after re-evaluation will receive nivolumab 360 mg IV in clinic once every three weeks.

In Part B, nivolumab 3 mg/kg AND ipilimumab (Yervoy, an immunotherapy) will both be given IV in clinic once every three weeks for four doses. Patients who remain on study after re-evaluation will receive nivolumab 360 mg IV in clinic once every three weeks.

The purpose of this study is to determine whether nivolumab (Opdivo, an immunotherapy) in combination with other therapies is more effective than nivolumab in combination with ipilimumab (Yervoy, an immunotherapy) in treating patients with advanced renal cell carcinoma. It is hypothesized that patients will have an increased clinical response (decrease in tumor size) when given a combination of nivolumab and BMS-986016 (an immunotherapy) than when given a combination of nivolumab and ipilumumab.

Nivolumab, ipilimumab, and the experimental drug BMS-986016 are all given intravenously (IV) in clinic. The dosing schedule will be either:

1. Nivolumab is given intravenously IV at 3mg/kg PLUS ipilimumab given IV at 1mg/kg once every 3weeks for 4 doses. Six weeks after the last dose of combination study, nivolumab will be given IV at 480 mg one every 4 weeks for 3 doses OR

2. Nivolumab is given IV at 240 mg PLUS BMS-986016 is given IV at 80 mg once every 2 weeks for 12 doses.

This is an open-label, multicenter, Phase 1, ascending dose escalation study of PSB205 (a type of immunotherapy) in subjects with advanced solid tumors, including bladder and kidney cancer. This study purpose is to describe the safety and tolerability, to assess Pharmacokinetics (PK, how the drug moves through your body) and immunogenicity (the effect on the immune system), and to preliminarily assess the anti-tumor activity of PSB205 in subjects with solid tumors. All subjects will receive study drug. Specific dosing will be provided by your treating physician. PSB205 will be administered on day 1 of every 21-day cycle (3 weeks) by intravenous (IV) infusion.

The purpose of this study is to test the safety of an investigational drug called CFI-402411 (a type of targeted therapy) alone and in combination with pembrolizumab (Keytruda, a type of immunotherapy) and to study its effects in patients with advanced solid tumors (including bladder and kidney cancer) who have progressed following previous therapies. This study has 2 treatment arms: Arm A: CFI-402411 alone CFI-402411 is administered orally (po or by mouth) once daily. The starting dose is 80 mg/day. Specific dose will be provided by your treating physician. Arm B: CFI-402411 + pembrolizumab CFI-402411 is administered orally (po or by mouth) once daily. The starting dose is 80 mg/day. Specific dose will be provided by your treating physician. Pembrolizumab will be given at, 200 mg administered as an intravenous (IV) infusion over 30 minutes every 3 weeks.

This is a single arm, single site, open-label Phase II study of the effects of oral olaparib (Lynparza, a type of targeted therapy, a PARP inhibitor) in participants with metastatic renal cell carcinoma that harbor an inactivating mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L who have had prior treatment with at least one immune checkpoint inhibitor (immunotherapy) or anti-VEGF therapy (targeted therapy). This study has 1 arm: Olaparib: Participants will be initially treated with olaparib 150 mg by mouth (PO) twice daily for one month. After one month of therapy, the dose will be increased to 300mg by mouth twice daily, if tolerated. Treatment will be continued until clinical and/or radiographic progression or unmanageable side effects requiring discontinuation of the drug.

Metastatic renal cell carcinoma (RCC) is an incurable condition. Current therapy for this disease consists of targeted therapies and immunotherapies. Long-term survival can be achieved however, of those patients treated with immunotherapy, three quarters will not respond at all and only 5-8% will achieve a complete and long term response. Gene transfer is a new cancer therapy that takes white blood cells from a person and grows them in a lab. The cells are changed with a virus to attack tumor cells, then returned to the person. Researchers want to see if this therapy fights kidney cancer cells. Our team isolated a tumor-specific cytotoxic T lymphocyte (CTL, a type of white blood cell that kills cancer cells) line from peripheral blood obtained after an allogeneic transplant from a patient who showed prolonged tumor regression. We identified a HERV-E derived antigen expressed in the patient s ccRCC cells to be the target of this T-cell clone. Remarkably, we found this HERV-E was expressed in the majority of ccRCC cells with no expression in normal tissues. This research protocol is designed to evaluate the safety and effectiveness of the infusion of HERV-E T cells. Treatment: • Participants will have leukapheresis. Blood will be removed by a needle in an arm. It will go through a machine that removes white blood cells. Plasma and red cells will be returned through a needle in the participant’s other arm. • Participants cells will be grown in the lab and genetically changed. • Participants will stay in the hospital 2-3 weeks. In the hospital participants will: • Get 2 chemotherapy drugs by catheter (thin plastic tube) inserted into a vein in the chest. • Get the changed cells via catheter. • Get a drug to increase white blood cell count and one to make the cells active. • Recover for about a week. • Have lab and blood tests. After leaving the hospital, participants will: • Take an antibiotic for several months. • Have leukapheresis. • Have one- or two-day clinic visits every few weeks for 2 years, and then as determined by their doctor. These will include blood and lab tests, imaging studies, and physical exam. • Participants will have follow-up checks for up to 15 years.

This is a Phase III, multicenter, randomized, open-label study designed to evaluate the effectiveness and safety of atezolizumab (Tecentriq, a type of immunotherapy) given in combination with cabozantinib (Cabometyx, a type of targeted therapy) versus cabozantinib alone in participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who experienced radiographic (seen on imaging scans like a CT scan) tumor progression during or after Immune Checkpoint Inhibitor (ICI, immunotherapy) treatment in the metastatic setting. This study has 2 arms: Arm A: Atezolizumab + Cabozantinib Atezolizumab 1200 mg will be administered by intravenous (IV) infusion every 3 weeks (on Day 1 of every 21 day cycle). Cabozantinib 60 mg (three 20-mg tablets) administered orally (by mouth or po) once daily. Arm B: Cabozantinib alone Cabozantinib 60 mg (three 20-mg tablets) administered orally (by mouth or po) once daily.

The main purpose of this study is to compare the overall response rate (ORR) and overall survival (OS) of NKTR-214 (a type of immunotherapy) combined with nivolumab (a type of immunotherapy) to that of a tyrosine kinase inhibitor (TKI, a type of targeted therapy) monotherapy in intermediate and poor-risk participants with previously untreated advanced renal cell carcinoma (RCC). This study has 2 arms: specific doses and dosing schedules to be provider by the participating site. Arm 1: Combination of NKTR-214 + Nivolumab Participants will receive NKTR-214 in combination with Nivolumab given intravenously (IV). Arm 2: Sunitinib (Sutent) or Cabozantinib (Cabometyx) Participants will receive the treating physician’s choice of either one of these two treatment options. Both drugs are taken by mouth.

This study is being performed as a single-arm open-label study in order to rapidly provide information on the potential benefits of the combination of pembrolizumab (Keytruda, a type of immunotherapy) and lenvatinib (Lenvima, a type of targeted therapy) in participants with previously untreated advanced/metastatic non-clear cell renal cell carcinoma. This study has 1 treatment arm: Pembrolizumab + Lenvatinib Pembrolizumab 400 mg given every 6 weeks (Q6W) intravenously (IV) for up to 18 infusions or up to progressive disease or discontinuation PLUS Lenvatinib 20 mg taken daily (QD), by mouth (orally or PO), until progressive disease or discontinuation.

The main purpose of this study are to determine the recommended dose regimen and the maximum tolerated dose, and to determine the safety of JNJ-63898081 (a type of immunotherapy). All subjects will receive treatment. JNJ-63898081 is a vaccine that will be administered at increasing dose levels. Specific dosing details will be provided by your treating physician.

Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug M9241 triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation. This study has 3 treatment arms: Arm A: Treatment with M7824 and deescalating (decreasing) doses of M9241, if appropriate Drug: M7824 1200 mg administered intravenously (IV) in clinic every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously (SC or SQ) every 4 weeks while on M7824 and with or without SBRT Arm B: Treatment with M7824 and deescalating doses of M9241 (if appropriate) with sequential SBRT Drug: M7824 1200 mg administered IV every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT Radiation: Stereotactic body radiation therapy (SBRT) a fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241 Arm C: Treatment with M7824 and deescalating doses of M9241 (if appropriate) with concurrent SBRT Drug: M7824 1200 mg administered IV every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT Radiation: Stereotactic body radiation therapy (SBRT) a fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241

This is a multi-arm, multicenter, open-label, combination cohort study designed to evaluate IPI-549 (Eganelisib, a type of immunotherapy) a first-in-class, oral immuno-oncology product candidate targeting immune-suppressive tumor-associated. IPI-549 will be administered in combinations with Tecentriq (Atezolizumab, a type of immunotherapy) and Avastin (Bevacizumab, a type of targeted therapy) patients with locally advanced and/or metastatic renal cell carcinoma (RCC). There is one treatment arm for patients with renal cell cancer: IPI-549 (eganelisib) IPI-549 is an orally-administered capsule that will be dosed at either 20mg/day, 30mg/day, or 40mg/day to patients. Atezolizumab Atezolizumab 840 mg of the drug will be administered intravenously (IV) on days 1 and 15 in combination of each 28-day cycle OR 1200mg will be administered IV on day 1 of each 21-day. Bevacizumab Bevacizumab will be administered at 15 mg/kg IV on day 1 of each 21-day cycle.

The primary objective of this study is to compare MK-6482 (a type of targeted therapy) to everolimus (Afinitor, a type of targeted therapy) with respect to progression-free survival (PFS, the time it takes your cancer to get larger) and to compare everolimus with respect to overall survival (OS, how long you live overall, whether your cancer grows or not). The belief is that MK-6482 will work better than everolimus with respect to PFS and OS. Treatment – this study has 2 arms Arm A: MK-6482 Participants receive 120 mg of MK-6482 orally (by mouth or PO) once daily. Arm B: Everolimus Participants receive 10 mg of Everolimus orally (by mouth or PO) once daily.