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 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.

This trial is a prospective, observational study is to understand the cancer management and health-related quality of life in patients with metastatic renal cell carcinoma (mRCC) in routine real-world clinical practice in the United States, including both community and academic treatment settings. Primarily, the study will evaluate patient experience through collection of patient reported outcomes (PROs). The study will also collect and assess information on the therapies used such as first-line treatment selection, treatment sequence and duration, the drivers of physician selection of particular agents, and discontinuation of therapies. The primary objective is to determine distinct patterns of change in the quality of life and symptom burden in mRCC patients receiving therapy. Patients will be identified and undergo consent and baseline assessments, including research blood collection and processing, by the study site team, this baseline visit will be their only clinic visits per protocol. All other visits are standard of care visits and outside the scope of the study.

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.

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 purpose of this study is to first, in Part 1, to determine the safety of nivolumab (Opdivo, a type of immunotherapy), bempegaldesleukin (BEMPEG: NKTR-214, a type of targeted therapy), and Tyrosine Kinase Inhibitor (TKI, a type of targeted therapy) combination and then, in Part 2, to evaluate the effectiveness of nivolumab, bempegaldesleukin, and cabozantinib when compared with nivolumab and cabozantinib in participants with previously untreated kidney cancer that has advanced or has spread. This study has 3 potential treatment arms: Arm A: Nivolumab + Bempegaldesleukin + Axitinib Nivolumab and Bempegaldesleukin are given intravenously (IV) in clinic. Axitinib (Inlyta, a type of targeted therapy) is an oral drug taken by mouth (PO). Dosing and schedule for all medications will be provided by the treatment team. Arm B: Nivolumab + Bempegaldesleukin + Cabozantinib Nivolumab and Bempegaldesleukin are given intravenously (IV) in clinic. Cabozantinib (Cabometyx, a type of targeted therapy) is an oral drug taken by mouth (PO). Dosing and schedule for all medications will be provided by the treatment team. Arm C: Nivolumab + Cabozantinib Nivolumab is given intravenously (IV) in clinic. Cabozantinib (Cabometyx, a type of targeted therapy) is an oral drug taken by mouth (PO). Dosing and schedule for all medications will be provided by the treatment team.

The purpose of this study is to assess the effectiveness and safety of oral belzutifan (MK-6482, Welireg, a type of targeted therapy) plus intravenous (IV) pembrolizumab (MK-3475, Keytruda, a type of immunotherapy) compared to placebo plus pembrolizumab, in the adjuvant treatment of Clear Cell Renal Cell Carcinoma (ccRCC) post nephrectomy. The primary study hypothesis is that belzutifan plus pembrolizumab is superior to placebo plus pembrolizumab with respect to disease-free survival (DFS). This study has 2 treatment arms: Arm A: Belzutifan + Pembrolizumab Participants receive belzutifan 120 mg orally (by mouth, PO) once daily for up to approximately 54 weeks PLUS pembrolizumab 400 mg via intravenous (IV) infusion once every 6 weeks for up to 9 administrations (up to approximately 54 weeks). Arm B: Placebo + Pembrolizumab Participants receive placebo orally once daily for up to approximately 54 weeks PLUS pembrolizumab 400 mg via IV infusion once every 6 weeks for up to 9 administrations (up to approximately 54 weeks).

This study will be comparing tivozanib (Fotivda, a type of targeted therapy) in combination with nivolumab (Opdivo, a type of immunotherapy) to tivozanib alone in subjects with advanced Renal Cell Carcinoma (RCC) who have had 1 or 2 prior lines of therapy, one of which was an Immune Checkpoint Inhibitor (ICI). The study is designed to compare the progression free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety of tivozanib and the combination of tivozanib with nivolumab. This study has 2 treatment arms: Arm A: Tivozanib + Nivolumab Subjects will receive 1.34 mg of tivozanib once daily (QD) by mouth (orally, PO) for 3 weeks followed by 1 week off study drug and nivolumab every 4 weeks intravenously (IV) on day 1 of each 4 week cycle, until disease progression or unacceptable toxicities occur, other withdrawal criteria are met, or completion of 2 years of treatment [for nivolumab] whichever occurs first. Arm B: Tivozanib Subjects will receive 1.34 mg of tivozanib once daily (QD) by mouth for 3 weeks followed by 1 week off study drug until disease progression or unacceptable toxicities occur, or other withdrawal criteria are met.