Merck: FDA approves KEYTRUDA and KEYTRUDA QLEX with WELIREG for adjuvant ccRCC
- FDA approved KEYTRUDA and KEYTRUDA QLEX each in combination with WELIREG for adjuvant clear cell RCC at intermediate‑high or high risk after nephrectomy.
- Phase 3 LITESPARK‑022 (N=1,841) showed a 28% reduction in risk of recurrence, metastasis or death (HR=0.72; p=0.0003); 24‑month DFS 81% vs 74%.
- Regimen and schedule: WELIREG 120 mg orally once daily plus KEYTRUDA 400 mg IV every six weeks for up to 9 cycles (54 weeks); control arm received KEYTRUDA plus oral placebo.
- Safety: serious adverse reactions in 30% of combination patients; WELIREG permanently discontinued in 27%; most common AEs included decreased hemoglobin (95%), increased ALT (57%), fatigue (49%) and hypoxia.
Regulatory approval
The U.S. FDA approved KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab with berahyaluronidase alfa) each in combination with WELIREG (belzutifan) for adjuvant treatment of adult patients with renal cell carcinoma with a clear cell component (ccRCC) at intermediate‑high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. These are the first approvals for WELIREG in earlier‑stage ccRCC and the first PD‑1 plus HIF‑2α inhibitor combinations approved.
Key trial results
Approvals were based on the randomized, double‑blind Phase 3 LITESPARK‑022 trial (N=1,841). The combination of KEYTRUDA plus WELIREG met the primary endpoint of investigator‑assessed disease‑free survival (DFS), reducing the risk of disease recurrence, metastasis or death by 28% versus KEYTRUDA plus placebo (HR=0.72; 95% CI 0.59–0.87; p=0.0003). Estimated 24‑month DFS rates were 81% (95% CI 0.78–0.83) with the combination versus 74% (95% CI 0.71–0.77) with KEYTRUDA plus placebo; median DFS was not reached in either arm. Overall survival data were not mature at the interim analysis.
Study design and dosing
Subjects were randomized 1:1 to WELIREG 120 mg orally once daily plus KEYTRUDA 400 mg IV every six weeks for up to 9 cycles (54 weeks) or KEYTRUDA plus oral placebo. Eligible patients had intermediate‑high or high risk of recurrence or M1 no evidence of disease and had not received prior systemic therapy for advanced RCC.
Safety and precautions
In LITESPARK‑022, serious adverse reactions occurred in 30% of patients receiving the combination; fatal adverse reactions occurred in 1.1%. WELIREG was permanently discontinued for adverse reactions in 27% of patients. The most common adverse reactions (≥25%) included decreased hemoglobin (95%), increased ALT (57%), fatigue (49%), increased AST (46%), decreased lymphocytes (38%), and increased alkaline phosphatase (29%). WELIREG carries a boxed warning for embryo‑fetal toxicity and can cause severe anemia and severe hypoxia; monitor pregnancy status, hemoglobin and oxygen saturation and advise effective non‑hormonal contraception.
Source: Merck
