The purpose of this research is to test the safety of PD-1 inhibitor cemiplimab with or without LAG-3 inhibitor fianlimab, and see what effects (good and bad) of cemiplimab either alone or combined with fianlimab has on patients with oligometastatic clear cell renal cell carcinoma after completion of radiation therapy.
All eligible patients will undergo standard of care SBRT to primary tumor (if present) and/or all metastatic tumor sites prior to randomization. During radiotherapy, patients will receive 1 to 5 fractions delivered over 1-2 weeks. Then patients will be randomized at 1:1 ratio to the two arms: * ARM A: Cemiplimab, 350 mg, IV, and Fianlimab 1600 mg, IV, q3w for 1 year, * ARM B: Cemiplimab 350 mg, IV, Q3W for 1 year. Immune check point inhibition will occur within 3 weeks (+/-1 week) of completion of SBRT Patients will undergo treatment with the study drug(s) every 3 weeks for a maximum of 17 cycles (approximately 12 months) or until disease recurrence, unacceptable toxic effects, or intercurrent illness preventing further administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
72
Cemiplimab is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells and was invented using Regeneron's proprietary Veloc Immune® technology. By binding to PD-1, cemiplimab (Libtayo) has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.
Fianlimab is a recombinant fully human monoclonal antibody (based on IgG4 isotype) targeting the immune checkpoint receptor LAG-3 on T cells and was invented using Regeneron's proprietary Veloc Immune® technology.
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
RECRUITINGProportion of patients with progression-free survival of oligo-metastatic clear cell renal cell carcinoma (ccRCC) patients following stereotactic body radiation therapy (SBRT) and up to one-year of treatment with cemiplimab or cemiplimab plus fianlimab.
Comparison of the 1-year progression-free survival between patients with oligo-metastatic ccRCC treated with cemiplimab alone versus those treated with both cemiplimab and fianlimab following SBRT.
Time frame: 1 year
Proportion of TRAEs for assessment of the overall safety profile of cemiplimab and fianlimab in patients with oligo-metastatic ccRCC.
Frequency and severity of TRAEs (Treatment Related Adverse Events), TEAEs (Treatment-Emergent Adverse Events), imAEs (immune-mediated Adverse Events) and SAEs (Severe Adverse Events) related to cemiplimab alone and of cemiplimab + fianlimab by using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria
Time frame: 1 year
Evaluation of the objective response rate (ORR) of cemiplimab and fianlimab
Proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST v1.1 criteria and Response Assessment in Neuro-Oncology (RANO)
Time frame: 1 year
Evaluation of the rates of local disease control in patients in response to SBRT with cemiplimab and fianlimab
Proportion of patients with a response rate measurement of time to local progression, measured as per iRECIST guidelines until the date of local progression for each lesion, with death considered a censoring event
Time frame: 1 year
Evaluation of the rates of distant disease control in patients in response to SBRT with cemiplimab and fianlimab
Proportion of patients with a response rate measurement of distant progression-free survival (DPFS), measured to the date of first distant progression at a site not documented at registration, or the date of death from any cause for patients without distant progression
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Time frame: 1 year
Evaluation of duration of response in patients in response to SBRT with cemiplimab and fianlimab
Proportion of patients with a response rate measurement of duration of response (DOR), defined as the time from first documented response (CR or PR) to disease progression or death from any cause
Time frame: 1 year
Evaluation of the Overall survival (OS) rate in patients in response to SBRT with cemiplimab and fianlimab
Proportion of patients with a response rate measurement defined as time of enrollment to death from any cause
Time frame: 1 year
Evaluation of the rates of disease control in patients in response to SBRT with cemiplimab and fianlimab
Proportion of patients achieving CR, PR, or stable disease (SD) from start of treatment
Time frame: 1 year