Cemiplimab and Fianlimab before Surgery for the Treatment of Patients with Locally Advanced Kidney Cancer Undergoing Nephrectomy
This phase II trial tests how well cemiplimab and fianlimab before surgery (neoadjuvant) works in treating patients with clear cell renal cell carcinoma (kidney cancer) that has spread to nearby tissue or lymph nodes (locally advanced) undergoing nephrectomy (surgery to remove a kidney or part of a kidney). Immunotherapy with monoclonal antibodies, such as cemiplimab and fianlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This approach may be most effective before surgery while the cancer is still present and accessible to the immune cells and that these immune effects will prevent the cancer from coming back in the future. Giving cemiplimab and fianlimab before surgery may kill more tumor cells in treating patients with locally advanced kidney cancer.
Inclusion Criteria
- Age ≥ 18 years at the time of informed consent.
- 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.
- Signed and dated Institutional Review Board (IRB)-approved informed consent form.
- Patients must be planned for nephrectomy for high risk non-metastatic clear cell renal cell carcinoma. * Non-metastatic disease will be defined by no evidence of metastases other than regional lymphadenopathy as assessed by imaging of the chest, abdomen and pelvis with CT of the chest and MR of the abdomen/pelvis (CT abdomen/pelvis will suffice for those unable to undergo MR imaging). * ‘High-risk non-metastatic’ is defined as those patients with a 12-year probability of metastases of > 40% as per an established pre-operative nomogram.
- Patients must undergo baseline biopsy to confirm clear cell histology prior to treatment initiation.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Absolute neutrophil count (ANC) ≥ 1500 cells/uL (without granulocyte colony stimulating factor support within 2 weeks prior to cycle 1, day 1) (within 14 days prior to the first study treatment).
- White blood cell (WBC) counts ≥ 2500/uL and ≤ 15,000/uL without granulocyte colony-stimulating factor (G-CSF) (within 14 days prior to the first study treatment).
- Absolute lymphocyte count ≥ 500/uL (within 14 days prior to the first study treatment).
- Platelet count ≥ 100,000/uL (without transfusion within 2 weeks prior to cycle 1, day 1) (within 14 days prior to the first study treatment).
- Hemoglobin ≥ 9.0 g/dL (without transfusion within 2 weeks prior to cycle 1, day 1) (within 14 days prior to the first study treatment).
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). Alkaline phosphatase (ALP) ≤ 5 x ULN if patient has documented bone metastases (within 14 days prior to the first study treatment).
- Serum bilirubin ≤ 1.5 x ULN. Patients with known Gilbert disease who have serum bilirubin level ≤ 2 x ULN may be enrolled (within 14 days prior to the first study treatment).
- Estimated glomerular filtration rate (eGFR) ≥ 40mL/min using the Chronic Kidney Disease Epidemiology (CKD-EPI) formula (within 14 days prior to the first study treatment).
Exclusion Criteria
- Prior receipt of any systemic therapy for renal cell carcinoma.
- Prior receipt of any immune checkpoint inhibitor therapy for any indication.
- Inability to safely delay surgery by 9 weeks as per surgeon’s discretion.
- Patients who are receiving any other investigational agents.
- History of allergic reactions or known hypersensitivity attributed to the active substances or to any of the excipients.
- History of severe hypersensitivity reaction to any monoclonal antibody.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring therapy, symptomatic congestive heart failure, unstable angina pectoris, or uncontrolled cardiac arrhythmia.
- Patients with a history of myocarditis.
- Patients with Troponin TnT or troponin I TnI > 2x institutional ULN at baseline. * Patients with TnT or TnI levels between > 1 to 2 x ULN are permitted if repeat levels within 24 hours are ≤ 1x ULN. If TnT or TnI levels are > 1 to 2 x ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment by the investigator based on the medical judgement in the patient¡¦s best interest.
- Patients with active autoimmune disease or recent history (within 2 years) of autoimmune disease that might recur, which may affect vital organ function, or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn’s, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event).
- Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
- Prior allogeneic stem cell transplant or solid organ transplant.
- History or current evidence of significant (CTCAE grade ≥ 2) local or systemic infection (eg, cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.
- Use of live vaccines against infectious disease (e.g. varicella) within 30 days of initiation of study therapy. Killed vaccinations (e.g. influenza) are allowed at any appropriate time before and during the study. If a patient intends to receive a COVID-19 vaccine before the start of study drug, participation in the study should be delayed at least 1 week after any COVID-19 vaccination. During the treatment period, it is recommended to delay COVID-19 vaccination until patients are receiving and tolerating a steady dose of study drug. A vaccine dose should not be less than 48 hours before or after study drug dosing.
- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus (HBV or HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection. * Patients with known HIV infection who have controlled infection (undetectable viral load on HIV RNA polymerase chain reaction [PCR]) and CD4 count above 350 (either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards. * Patients with HBV (hepatitis B surface antigen positive; HBsAg+) who have controlled infection (serum HBV deoxyribonucleic acid [DNA] PCR that is below the limit of detection and receiving anti-viral therapy for HBV) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months after the last dose of cemiplimab. * Patients who are HCV antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR, either spontaneously or in response to successful prior course of anti-HCV therapy) are permitted. * Patients with HIV or hepatitis must be reviewed by a qualified specialist (e.g., infectious disease or hepatologist) managing this disease prior to commencing and regularly throughout the duration of their participation in the trial.
- Women with a positive serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening/baseline visit. If positive, pregnancy must be ruled out by ultrasound for patient to be eligible.
- Breast-feeding women.
- Women of childbearing potential (WOCBP) who are sexually active and are not willing to practice highly effective contraception prior to the first treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include: * Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening; * Intrauterine device; intrauterine hormone-releasing system; * Bilateral tubal occlusion/ligation; * Vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure); and/or * Sexual abstinence - Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
- Male study participants with WOCBP partners are required to use condoms during the study and until 6 months after the last dose of study treatment unless they are vasectomized or practice sexual abstinence.
- WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial and until 6 months after last treatment.
- All men must agree not to donate sperm during the trial and for 6 months after receiving the last therapy dose.
Additional locations may be listed on ClinicalTrials.gov for NCT06699602.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Middletown
Montvale
New York
Commack
New York
Uniondale
West Harrison
PRIMARY OBJECTIVE:
I. Determine feasibility of neoadjuvant cemiplimab + fianlimab followed by nephrectomy, defined as patients’ ability to receive therapy and undergo surgery without significant delay (> 116 days from start of neoadjuvant treatment).
SECONDARY OBJECTIVES:
I. Assess safety and tolerability of treatment by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
II. Assess surgical safety by Clavien-Dindo Classification.
III. Determine objective response on post-treatment, pre-operative imaging.
IV. Determine pathologic complete response.
V. Determine the proportion of patients who do not meet criteria for adjuvant pembrolizumab per KEYNOTE 564.
EXPLORATORY OBJECTIVES:
I. Evaluate the association between baseline tumor mutational burden and both immune infiltration and radiographic tumor response to cemiplimab + fianlimab.
II. Explore predicted and expressed tumor neoantigens and their correlation with radiographic tumor response to cemiplimab + fianlimab.
III. Explore the association between the predicted immune signature (via ribonucleic acid [RNA] sequencing) in the tumor microenvironment with radiographic tumor response to cemiplimab + fianlimab.
IV. Explore whether changes in the tumor microenvironment and peripheral blood before, during, and after therapy are associated with response.
V. Assess the potential association between PD-L1 and LAG-3 expression (by immunohistochemistry) and radiographic tumor response to cemiplimab + fianlimab.
OUTLINE:
Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 of each cycle and fianlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy during screening, computed tomography (CT) and magnetic resonance imaging (MRI) during screening and on study and blood sample collection throughout the study. Patients also undergo standard of care (SOC) nephrectomy post-treatment.
After completion of study treatment, patients are followed up at 1-3 and 14-28 days then 90 days after surgery.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorMartin Henner Voss
- Primary ID24-329
- Secondary IDsNCI-2025-01109
- ClinicalTrials.gov IDNCT06699602