Ipilimumab

The purpose of this study is to evaluate the safety and tolerability of Pumitamig alone or in combination with Ipilimumab in participants with first-line advanced or unresectable Hepatocellular Carcinoma (HCC)

The purpose of this study is to evaluate the safety, tolerability, and efficacy of Pumitamig alone or in combination with Ipilimumab or Cabozantinib in participants with advanced Renal Cell Carcinoma (RCC)

This phase I trial tests the safety and effectiveness of nivolumab and ipilimumab with and without EXL01 for the treatment of renal cell cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. EXL01 is a live biotherapeutic product containing a strain of bacteria called Faecalibacterium prausnitzii. It may enhance a patient's response to treatment with immune checkpoint inhibitors like nivolumab and ipilimumab by altering the composition of the bacteria in the gut. Adding EXL01 to treatment with nivolumab and ipilimumab may be safe and more effective than giving nivolumab and ipilimumab alone.

This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 alone for the treatment of patients with radiographically-confirmed progression of Astrocytoma IDH- mutant, Glioblastoma IDH-wildtype, and the safety, pharmacokinetics and efficacy of a repeated dose regimen of NEO212 when given with select SOC for the treatment of solid tumor patients with radiographically confirmed uncontrolled metastases to the brain. The study will have three phases, Phase 1, Phase 2a and Phase 2b.

This phase II trial tests whether the combination of nivolumab and ipilimumab is better than nivolumab alone to shrink tumors in patients with deficient mismatch repair system (dMMR) endometrial carcinoma that has come back after a period of time during which the cancer could not be detected (recurrent). Deoxyribonucleic acid (DNA) mismatch repair (MMR) is a system for recognizing and repairing damaged DNA. In 2-3% of endometrial cancers this may be due to a hereditary condition resulted from gene mutation called Lynch Syndrome (previously called hereditary nonpolyposis colorectal cancer or HNPCC). MMR deficient cells usually have many DNA mutations. Tumors that have evidence of mismatch repair deficiency tend to be more sensitive to immunotherapy. There is some evidence that nivolumab with ipilimumab can shrink or stabilize cancers with deficient mismatch repair system. However, it is not known whether this will happen in endometrial cancer; therefore, this study is designed to answer that question. 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 nivolumab in combination with ipilimumab may be better than nivolumab alone in treating dMMR recurrent endometrial carcinoma.

This phase I trial investigates the effects of influenza vaccine in treating patients with stage I-IV melanoma. While intramuscular administration of influenza vaccine provides immunization against the influenza virus, giving influenza vaccine directly into the tumor (intralesional) may decrease the size of the injected melanoma tumor, or the extent of the melanoma within the body.

This is a single center, phase Ib/II study combining an anti-PD-1 antibody and an anti-CTLA-4 antibody with IL-15. It is testing the hypothesis that the addition of nogapendekin alfa inbakicept to nivolumab and ipilimumab will augment the clinical activity of those two drugs.

The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) has significantly improved clinical outcomes in patients with advanced renal cell carcinoma (RCC). However, 40%-60% of patients still develop primary or acquired resistance. For those with resistant disease, current immune rechallenge strategies have yet to demonstrate clear clinical benefit. Emerging evidence indicates that the gut microbiota plays a critical role in modulating responses to immunotherapy. Microbiota-modulating approaches, including fecal microbiota transplantation (FMT) and live bacterial formulations such as CBM588, have shown preliminary potential to enhance sensitivity to immunotherapy and improve patient outcomes. Nevertheless, whether gut microbiota modulation can resensitize advanced RCC to immunotherapy remains to be investigated. The REMEDY-RCC trial is an investigator-initiated, prospective, open-label, phase II, parallel two-cohort exploratory study primarily designed to investigate whether gut microbiota modulation can restore sensitivity to immunotherapy in patients with advanced RCC. Given the substantial differences in the tumor immune microenvironment and response to ICIs between clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC), this study employs a parallel two-cohort design to stratify these two patient populations: a primary cohort consisting of patients with metastatic ccRCC, and an exploratory cohort consisting of patients with metastatic nccRCC. The primary and secondary endpoints will be analyzed in the primary cohort, whereas the exploratory cohort will be used solely for exploratory and descriptive analyses. The study plans to enroll approximately 33 adult patients with advanced or metastatic RCC, including 27 with metastatic ccRCC and 6 with metastatic nccRCC. Eligible patients will receive the following sequential interventions: bowel decontamination with amoxicillin-clavulanate potassium followed by polyethylene glycol (PEG) solution, high-dose gut colonization and maintenance supplementation with live Clostridium butyricum powder combined with soluble dietary fiber, and immune rechallenge therapy consisting of a PD-1 immune checkpoint inhibitor (ICI) combined with four cycles of a CTLA-4 ICI, followed by maintenance therapy with the PD-1 ICI alone. Treatment will continue until disease progression, unacceptable toxicity, completion of the planned treatment cycles, or withdrawal of consent. The REMEDY-RCC trial requires specific follow-up for enrolled patients. Radiological response is assessed longitudinally using computed tomography (CT). Tissue and body fluid samples collected from patients will be used for biomarker and multi-omic analyses. The primary endpoint of the trial is the objective response rate (ORR) in the primary cohort, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Sample size for the primary cohort was determined using Simon's optimal two-stage design, with a one-sided α of 0.10 and power (1-β) of 0.80. The unacceptable response rate (P0) was set at 17.4%, based on the ORR observed in the FRACTION-RCC study for nivolumab plus ipilimumab rechallenge in patients with metastatic ccRCC who had progressed after prior immunotherapy. The target response rate (P1) was established considering that FMT has been shown to increase ORR by approximately 20% in immunotherapy-resistant melanoma. Given that metastatic RCC and melanoma are both considered immunologically responsive tumor types, a comparable therapeutic benefit from gut microbiota remodeling is anticipated. Accordingly, P1 was set at 37.4%. This effect size is clinically meaningful and would be non-inferior to the clinical efficacy of cabozantinib in metastatic RCC that has progressed following immunotherapy. The primary cohort will initially enroll six patients for safety assessment. If the treatment is deemed safe, further accrual will follow Simon's two-stage design, and enrollment of the exploratory cohort will be considered. After these six patients, an additional six patients will be enrolled, bringing the total to 12, at which point an interim analysis will be performed. If the number of objective responses at the interim analysis is ≤ 2, the trial will be terminated early. If ≥3 objective responses are observed, an additional 12 patients will be enrolled, resulting in a total sample size of 24 patients. Accounting for a potential 10% dropout rate, the study plans to enroll 27 patients in total. The exploratory cohort is planned to enroll no more than 6 patients (not exceeding 20% of the total enrollment), with a fixed-sample descriptive design. The sample size calculation is not based on statistical hypothesis testing, and all efficacy endpoints will be reported using descriptive statistics. The total planned sample size is 33 patients, comprising 27 patients in the primary cohort and 6 patients in the exploratory cohort.

The purpose of this study is to learn about the effects of study medicine (PF-08634404) when given alone or with another antibody (ipilimumab) for the treatment of a type of liver cancer called hepatocellular carcinoma (HCC) that is either locally advanced (spread to nearby tissues) or has spread to other parts of the body. To join the study, participants must meet the following conditions: * Be 18 years or older. * Have locally advanced or metastatic HCC. * Is not a candidate for complete surgical or loco-regional therapies. * Have not received any whole-body treatment for HCC. Participants will receive PF-08634404 either alone or in combination with ipilimumab. The medicine will be given through intravenous (IV) infusions, which means it will be administered directly into a vein. All treatments will take place at clinical trial sites, where trained medical staff will monitor participants during and after each visit.

This study is testing a new medicine called PF-08634404 and how it works in adults with advanced Renal Cell Carcinoma (RCC)- a type of kidney cancer that is either locally advanced (spread to nearby tissues) or metastatic (spread to other parts of the body). The study will look at the safety of the study medicine, when given alone or with other anticancer medicines, and how this type of cancer responds to them. To join the study, participants must be adults; with locally advanced or metastatic RCC; who have not received treatment for their advanced kidney cancer. Participants will receive study medicine either alone or with other anticancer medicines. The medicine will be given through intravenous (IV) infusions, which means it will be injected directly into a vein. All treatments will take place at clinical study sites, where trained medical staff will take care of participants during and after each visit.

This is a phase 2 single-arm, open-label clinical trial determining efficacy of cabozantinib in combination with ipilimumab/nivolumab and transarterial chemoembolization (TACE) in subjects with hepatocellular carcinoma (HCC). These are subjects who are not candidates for curative intent treatment.

This three-arm randomized phase 2 trial will enroll advanced clear cell RCC patients (all IMDC risk groups). Patients will be randomized 2:2:1 to either Arm A (fianlimab/ cemiplimab/ ipilimumab), Arm B (fianlimab/ cemiplimab), or Arm C (standard ipilimumab/ nivolumab), respectively.

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.

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 or zimberelimab or zimberelimab and ipilimumab in participants with ccRCC in the dose expansion stage.

The goal of this clinical trial is to study the impact of Neoadjuvant ipilimumab and nivolumab for melanoma patients that had recurrence during or after adjuvant anti-PD-1 therapy. Participants will receive 2 cycles of treatment prior to their standard of care surgery. After surgery participants will receive standard of care adjuvant therapy and be followed for response.

To determine whether short-term pre-operative nivolumab either as monotherapy or in combination with low dose doxorubicin or novel IO combinations can induce immune activation in early BC.

This phase I trial tests the safety, side effects, and best dose of a personalized vaccine (tumor membrane vesicle or TMV vaccine) by itself and in combination with checkpoint inhibitor (pembrolizumab or ipilimumab) in treating patients with triple negative breast cancer. This vaccine is made by taking a piece of patient's triple negative breast cancer to design a vaccine to stimulate the immune system's memory. Patients are treated with the personalized vaccine immunotherapy with or without monoclonal antibodies, such as pembrolizumab and ipilimumab. This approach may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving personalized TMV vaccine with pembrolizumab or ipilimumab may help the immune system attack cancer better and reduce the risk of this breast cancer coming back or growing.

This is a single center, non-blinded, multi-cohort, non-comparative phase II trial to study the safety and efficacy of tiragolumab with atezolizumab and/or ipilimumab in advanced triple-negative breast cancer.