Venous tumor thrombus (VTT) in patients with renal cell carcinoma (RCC) represents an aggressive disease feature associated with poor prognosis and management challenges. The efficacy of immunotherapy-based combinations in this subgroup remains insufficiently characterized. Methods: The PELET trial is an ambispective study enrolling adult patients with histologically confirmed advanced RCC and unresected VTT. Patients received lenvatinib 20 mg orally once daily in combination with pembrolizumab 200 mg intravenously every 3 weeks. The primary endpoint was a ≥30% reduction in thrombus size. Secondary endpoints included changes in thrombus level, progression-free survival (PFS), and safety. Results: Twenty patients were included, predominantly male (85%), with a median age of 58.5 years. Most had clear cell histology (90%) and no sarcomatoid features. The median baseline thrombus size was 6.55 cm, which decreased to 3.0 cm after at least 12 weeks of therapy (p < 0.001). A ≥30% reduction in thrombus size was achieved in 45% of patients, meeting the primary endpoint. Moreover, 35% experienced a reduction in thrombus length > 50%, and 45% demonstrated a decrease in thrombus level by at least one level. Thrombus response was not correlated with baseline thrombus size. Median PFS was not reached at the time of analysis. Grade ≥3 adverse events occurred in 15% of patients. Conclusions: Twenty patients were included, predominantly male (85%), with a median age of 58.5 years. Most had clear cell histology (90%) and no sarcomatoid features. The median baseline thrombus size was 6.55 cm, which decreased to 3.0 cm after at least 12 weeks of therapy (p < 0.001). A ≥30% reduction in thrombus size was achieved in 45% of patients, meeting the primary endpoint. Moreover, 35% experienced a reduction in thrombus length > 50%, and 45% demonstrated a decrease in thrombus level by at least one level. Thrombus response was not correlated with baseline thrombus size. Median PFS was not reached at the time of analysis. Grade ≥3 adverse events occurred in 15% of patients. Clinical trial information: KCRB-092025-01.