KEY TAKEAWAYS
- The LITESPARK-022 (NCT05239728) is a global, multicenter, double-blind, randomized, phase 3 trial.
- The study’s primary aim is to evaluate the effectiveness and safety of belzutifan + pembrolizumab versus placebo + pembrolizumab.
- The study will enroll approximately 1600 patients diagnosed with ccRCC and fall under the intermediate-high high.
- The principal endpoint is DFS, evaluated by the investigator. The primary endpoint of interest is the OS.
- Patients will receive Pembrolizumab treatment for 9 doses, approximately 1 year.
- The co-administration of belzutifan and pembrolizumab can serve as a therapeutic modality for adjuvant management of ccRCC.
Recurrence may be observed in patients diagnosed with locally advanced renal cell carcinoma (RCC) after surgical intervention. The adjuvant pembrolizumab has significantly improved disease-free survival (DFS) in ccRCC during the phase 3 KEYNOTE-564 (NCT03142334) trial. This has led to the FDA’s approval of pembrolizumab on November 17, 2021, for adjuvant treatment of patients with RCC at intermediate-high or high risk for recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. Although pembrolizumab has demonstrated benefits, there is a demand for more efficacious adjuvant therapy options for patients susceptible to recurrence following definitive surgical intervention. Belzutifan (MK-6482), an inhibitor of HIF-2α, has demonstrated efficacy and favorable tolerability in individuals with advanced clear cell renal cell carcinoma (ccRCC) and renal cell carcinoma (RCC) associated with von Hippel-Lindau (VHL) disease. The co-administration of belzutifan and pembrolizumab could be a therapeutic modality for adjuvant management of clear cell renal cell carcinoma (ccRCC).
The LITESPARK-022 (NCT05239728) study is a global, multicenter, double-blind, randomized, phase 3 trial to evaluate the effectiveness and safety of belzutifan + pembrolizumab versus placebo + pembrolizumab as adjuvant therapy for ccRCC following nephrectomy. The study will enroll around 1600 patients diagnosed with RCC through histological or cytological confirmation. These patients will fall under the intermediate-high category (pT2, grade 4 or sarcomatoid, N0, M0 or pT3, any grade, N0, M0), high category (pT4, any grade, N0, M0 or pT, any stage/grade, N+, M0), or M1 NED category (patients who present with the primary kidney tumor and solid, isolated, soft tissue metastases that can be resected at the time of nephrectomy or ≤2 years from nephrectomy). These patients will have a clear cell component and have not previously received systemic therapy. The inclusion criteria necessitate that the patients should have undergone nephrectomy and/or metastasectomy within 12 weeks before randomization. The patients must be confirmed to be tumor-free through CT/MRI. The stratification factors encompass tumor grade, categorized as either 1 or 2 versus 3 or 4, and risk type, which includes intermediate-high, high, and M1 NED. The subjects will be randomized in a 1:1 ratio to obtain belzutifan 120 mg orally once daily along with pembrolizumab 400 mg IV every 6 weeks (Q6W) or oral placebo + pembrolizumab 400 mg IV Q6W.
The patient will receive Pembrolizumab treatment for 9 doses, approximately 1 year. Belzutifan and placebo may be continued for a maximum of 54 weeks. Radiological assessment will be conducted every 12 weeks from randomization until the end of year 2, every 16 weeks from years 3 to 5, and every 24 weeks from year 6 onwards to evaluate the recurrence of the disease. The NCI CTCAE v5.0 will be utilized to monitor any untoward medical occurrences (adverse events or AEs) for 30 days (90 days for severe AEs) following medication discontinuation. The principal endpoint is disease-free survival (DFS), evaluated by the investigator. It is characterized as the duration between randomization and the initially recorded incidence of local recurrence, distant metastasis of kidney cancer, or mortality from any cause, whichever arises first. The primary endpoint of interest is the overall survival. Additional secondary endpoints include evaluating the safety of the treatment, assessing disease recurrence-specific survival, and obtaining patient-reported outcomes.
Source:https://meetings.asco.org/abstracts-presentations/213049
Clinical Trail:https://clinicaltrials.gov/ct2/show/NCT05239728
Toni K. Choueiri, Jens Bedke, Jose A. Karam, Rana R. McKay, Robert J. Motzer, Sumanta K. Pal, Cristina Suárez, Robert Uzzo, Hong Liu, Joseph E. Burgents, Manish Sharma, Thomas Powles/LITESPARK-022: A phase 3 study of pembrolizumab + belzutifan as adjuvant treatment of clear cell renal cell carcinoma (ccRCC)/J Clin Oncol 40, 2022 (suppl 16; abstr TPS4602) DOI10.1200/JCO.2022.40.16_suppl.TPS4602
