Cemiplimab + Fianlimab for Kidney Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Overseen byMartin Voss, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must not be taking: Immune checkpoint inhibitors, Corticosteroids
Disqualifiers: Autoimmune disease, Uncontrolled infection, Recent malignancy, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The researchers are doing this study to find out whether it is practical (feasible) to give cemiplimab and fianlimab before a nephrectomy and whether it causes any delays with surgery in people with kidney cancer. The researchers will also look at whether cemiplimab and fianlimab given before a nephrectomy is a safe and effective treatment approach and if there is a change in the size of the tumor following immunotherapy prior to planned surgery.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study treatment. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination Cemiplimab and Fianlimab for kidney cancer?
The combination of immune checkpoint inhibitors, like those in Cemiplimab and Fianlimab, has shown promise in treating kidney cancer, as similar combinations have been effective in improving survival and response rates in patients with advanced renal cell carcinoma.
12345What makes the drug Cemiplimab + Fianlimab unique for kidney cancer?
Cemiplimab + Fianlimab is unique because it combines two immune checkpoint inhibitors, which may enhance the body's immune response against kidney cancer cells. This combination is different from standard treatments that often pair immunotherapy with tyrosine kinase inhibitors, offering a novel approach to potentially improve treatment outcomes.
678910Eligibility Criteria
This trial is for individuals with clear cell renal cell carcinoma, a type of kidney cancer. Participants should be candidates for nephrectomy (kidney removal surgery) and must not have conditions that could delay surgery or affect the safety and effectiveness of the immunotherapy drugs cemiplimab and fianlimab.Inclusion Criteria
I am 18 years old or older.
Patient must be able to provide informed consent, or a legal authorized representative (LAR) must be identified to provide consent in cases where the patient cannot
I have had a biopsy confirming clear cell cancer before starting treatment.
+4 more
Exclusion Criteria
Patients with Troponin TnT or troponin I TnI > 2x institutional ULN at baseline
I have previously received immunotherapy.
I haven't taken steroids or immunosuppressants in the last 14 days.
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive cemiplimab and fianlimab every 3 weeks for a total of 3 treatments
9 weeks
3 visits (in-person)
Surgery
Participants undergo nephrectomy following treatment with cemiplimab and fianlimab
1 week
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment and surgery
1 year
Participant Groups
The study tests if giving two immunotherapy drugs, cemiplimab and fianlimab, before kidney removal surgery is feasible without causing delays. It also examines their safety, effectiveness in shrinking tumors pre-surgery, and overall impact on treatment outcomes.
1Treatment groups
Experimental Treatment
Group I: Cemiplimab and FianlimabExperimental Treatment2 Interventions
All patients will be treated as follows: cemiplimab and fianlimab every 3 weeks for a total of 3 treatments, or until unacceptable toxic effects, overt disease progression, or withdrawal from study.
Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:
πͺπΊ Approved in European Union as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
- Non-small cell lung cancer (NSCLC)
πΊπΈ Approved in United States as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
- Basal cell carcinoma (BCC)
- Non-small cell lung cancer (NSCLC)
π¨π¦ Approved in Canada as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
- Non-small cell lung cancer (NSCLC)
π§π· Approved in Brazil as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activites)Basking Ridge, NJ
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Middletown, NJ
Memorial Sloan Kettering Bergen (Limited Protocol Activities)Montvale, NJ
Memorial Sloan Kettering West Harrison (Limited Protocol Activities)Harrison, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
Drug Combo Bests Sunitinib in RCC. [2019]The phase III IMmotion151 trial found that the combination of atezolizumab and bevacizumab boosts progression-free survival compared with sunitinib in patients with advanced or metastatic renal cell carcinoma. The increase was 2.8 months in all patients and 3.5 months in patients with PD-L1-positive tumors.
Exploratory Pilot Study of Circulating Biomarkers in Metastatic Renal Cell Carcinoma. [2020]With the introduction of immune checkpoint inhibitors (ICIs) and next-generation vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), the survival of patients with advanced renal cell carcinoma (RCC) has improved remarkably. However, not all patients have benefited from treatments, and to date, there are still no validated biomarkers that can be included in the therapeutic algorithm. Thus, the identification of predictive biomarkers is necessary to increase the number of responsive patients and to understand the underlying immunity. The clinical outcome of RCC patients is, in fact, associated with immune response. In this exploratory pilot study, we assessed the immune effect of TKI therapy in order to evaluate the immune status of metastatic renal cell carcinoma (mRCC) patients so that we could define a combination of immunological biomarkers relevant to improving patient outcomes. We profiled the circulating levels in 20 mRCC patients of exhausted/activated/regulatory T cell subsets through flow cytometry and of 14 immune checkpoint-related proteins and 20 inflammation cytokines/chemokines using multiplex Luminex assay, both at baseline and during TKI therapy. We identified the CD3+CD8+CD137+ and CD3+CD137+PD1+ T cell populations, as well as seven soluble immune molecules (i.e., IFNγ, sPDL2, sHVEM, sPD1, sGITR, sPDL1, and sCTLA4) associated with the clinical responses of mRCC patients, either modulated by TKI therapy or not. These results suggest an immunological profile of mRCC patients, which will help to improve clinical decision-making for RCC patients in terms of the best combination of strategies, as well as the optimal timing and therapeutic sequence.
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-Ξ³ 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.
In silico modeling of combination systemic therapy for advanced renal cell carcinoma. [2023]Therapeutic combinations of VEGFR tyrosine kinase inhibitor plus immune checkpoint blockade now represent a standard in the first-line management of patients with advanced renal cell carcinoma. Tumor molecular profiling has shown notable heterogeneity when it comes to activation states of relevant pathways, and it is not clear that concurrent pursuit of two mechanisms of action is needed in all patients. Here, we applied an in silico drug model to simulate combination therapy by integrating previously reported findings from individual monotherapy studies. Clinical data was collected from prospective clinical trials of axitinib, cabozantinib, pembrolizumab and nivolumab. Efficacy of two-drug combination regimens (cabozantinib plus nivolumab, and axitinib plus pembrolizumab) was then modeled assuming independent effects of each partner. Reduction in target lesions, objective response rates (ORR), and progression-free survival (PFS) were projected based on previously reported activity of each agent, randomly pairing efficacy data from two source trials for individual patients and including only the superior effect of each pair in the model. In silico results were then contextualized to register phase III studies of these combinations with similar ORR, PFS, and best tumor response. As increasingly complex therapeutic strategies emerge, computational tools like this could help define benchmarks for trial designs and precision medicine efforts. Summary statement: In silico drug modeling provides meaningful insights into the effects of combination immunotherapy for patients with advanced kidney cancer.
[Immunotherapy of Renal Cell Carcinoma]. [2019]Treatment of renal cell carcinoma is still palliative. Targeted therapy increases response rates and prolongs overall survival and progression-free survival compared with cytokines and chemotherapy. Checkpoint inhibitors constitute the up-date of therapeutic approaches, and anti-PD-1 antibody, one checkpoint inhibitor, is now well established as a second and/or third palliative treatment for patients with renal cell carcinoma. In this study, we present the latest data from current studies on cytokines, cancer vaccines, ipilimumab, and nivolumab. The therapeutic efficacies of combinations such as targeted therapy with immune checkpoint inhibitors and anti-CTLA-4 with anti PD-1 (-L1) have been reported in many studies. Preliminary results are encouraging but the high toxicities and elevated cost are limiting. Treatments with combinations of bevacizumab and atezolizumab, axitinib and pembrolizumab or avelumab, lenvatinib and pembrolizumab, and nivolumab and ipilimumab (results from study phase I, II, and sometimes III) are reported to be highly effective and to result in long-lasting responses with response-rates of 70-100%. So far, valid predictors for these therapies have not been forthcoming, but considerable work is being exerted in this area. Heng and Memorial Sloan Kettering Cancer Center (MSKCC) models are still being used to select patients for immunotherapy. Immunotherapy will definitely continue to play an important role in the treatment of patients with renal cell carcinoma; however, many questions remain.Key words: renal cell carcinoma - immunotherapy - checkpoint inhibitors - target therapy Supported by MH CZ - DRO (MMCI, 00209805) This work was supported by program of the Czech Ministry of Health No. P03-15-34 678A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 16. 8. 2017Accepted: 7. 9. 2017.
Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma. [2023]Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host's immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.
Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Français d'Immunothérapie. [2018]A phase II trial was designed to determine the efficacy and the tolerance of interleukin-2 (IL-2), interferon alfa-2a (IFNalpha), and fluorouracil (5-FU) in patients with metastatic renal cell carcinoma.
Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. [2023]Immunotherapy-based combinations including pembrolizumab plus lenvatinib are the standard of care for patients with first-line clear-cell renal cell carcinoma, but these combinations are not well characterised in non-clear-cell renal cell carcinoma. We aimed to assess the activity and safety of pembrolizumab plus lenvatinib as a first-line treatment for patients with advanced non-clear-cell renal cell carcinoma.
Phase I and II trials of subcutaneously administered rIL-2, interferon alfa-2a, and fluorouracil in patients with metastatic renal carcinoma. [2019]A phase I followed by a phase II trial utilizing rIL-2, IFN alpha, and 5-FU were conducted in patients with unresectable and/or metastatic renal cell carcinoma.
A Novel PD-L1 Antibody Promotes Antitumor Function of Peripheral Cytotoxic Lymphocytes after Radical Nephrectomy in Patients with Renal Cell Carcinoma. [2023]The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients and clinicians because no reliable tool has been developed to predict individualized response to immunotherapy. In this study, we demonstrate the translational relevance of an ex vivo functional assay that measures the tumor cell killing ability of patient-derived CD8 T and NK cells (referred to as "cytotoxic lymphocytes," or CLs) isolated from the peripheral blood of patients with renal cell carcinoma. Patient-derived PBMCs were isolated before and after nephrectomy from patients with renal cell carcinoma. We compared the efficacy of U.S. Food and Drug Administration (FDA)-approved PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, atezolizumab) and a newly developed PD-L1 inhibitor (H1A Ab) in eliciting cytotoxic function. CL activity was improved at 3 mo after radical nephrectomy compared with baseline, and it was associated with higher circulating levels of tumor-reactive effector CD8 T cells (CD11ahighCX3CR1+GZMB+). Treatment of PBMCs with FDA-approved PD-1/PD-L1 inhibitors enhanced tumor cell killing activity of CLs, but a differential response was observed at the individual-patient level. H1A demonstrated superior efficacy in promoting CL activity compared with FDA-approved PD-1/PD-L1 inhibitors. PBMC immunophenotyping by mass cytometry revealed enrichment of effector CD8 T and NK cells in H1A-treated PBMCs and immunosuppressive regulatory T cells in atezolizumab-treated samples. Our study lays the ground for future investigation of the therapeutic value of H1A as a next-generation immune checkpoint inhibitor and the potential of measuring CTL activity in PBMCs as a tool to predict individual response to immune checkpoint inhibitors in patients with advanced renal cell carcinoma.