Merck Receives Fda Approval for KEYTRUDA, KEYTRUDA QLEX, and WELIREG Combinations for Adjuvant Treatment of Clear Cell Renal Cell Carcinoma

Merck announced the U.S. Food and Drug Administration (FDA) approved KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph), each in combination with WELIREG (belzutifan), for the 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 approvals represent the first approval for WELIREG in earlier-stage ccRCC and the first approvals for PD-1 and HIF-2a inhibitor combination regimens. The approvals are based on results from the pivotal Phase 3 LITESPARK-022 trial.

LITESPARK-022 enrolled 1,841 patients and demonstrated that KEYTRUDA in combination with WELIREG significantly improved disease-free survival (DFS), the trial?s primary endpoint, reducing the risk of disease recurrence, metastasis or death by 28% (HR=0.72 [95% CI 0.59-0.87]; p=0.0003) for patients with ccRCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions compared to KEYTRUDA plus placebo. The estimated 24-month DFS rate was 81% (95% CI 0.78-0.83) with KEYTRUDA plus WELIREG compared to 74% (95% CI 0.71-0.77) with KEYTRUDA plus placebo. Median DFS was not reached in either arm.

Overall survival (OS) results were not yet mature at this interim analysis. The effectiveness of KEYTRUDA QLEX for its approved indications has been established based upon evidence from the adequate and well-controlled studies conducted with KEYTRUDA and additional data from MK-3475A-D77 comparing the pharmacokinetic, efficacy, and safety profiles of KEYTRUDA QLEX and KEYTRUDA. The WELIREG prescribing information contains a boxed warning that exposure to WELIREG during pregnancy can cause embryo-fetal harm.

Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective.

WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment with WELIREG. WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen or hospitalization.

Monitor oxygen saturation before initiation of, and periodically throughout, treatment with WELIREG. KEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients. KEYTRUDA and KEYTRUDA QLEX are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions in any or multiple organs, which can occur during or after treatment, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, other transplant (including corneal graft) rejection; severe and life-threatening infusion or injection-related reactions; fatal and other serious complications in patients who receive allogeneic hematopoietic stem cell transplantation before or after beginning treatment; embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when KEYTRUDA or KEYTRUDA QLEX is added to a thalidomide analogue plus dexamethasone, which is not recommended outside of controlled trials.

LITESPARK-022 is a multicenter, randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT05239728) evaluating WELIREG in combination with KEYTRUDA compared to placebo plus KEYTRUDA for the adjuvant treatment of ccRCC post nephrectomy. Eligible patients had intermediate-high or high risk of recurrence of RCC, or M1 no evidence of disease (NED). Patients must have undergone a partial or radical nephrectomy, and if indicated, metastasectomy within two years of nephrectomy, within =4 weeks prior to the time of screening.

Patients were excluded from the trial if they had received prior systemic therapy for advanced RCC. The trial enrolled 1,841 patients who were randomized (1:1) to receive either: WELIREG (120 mg orally once daily) plus KEYTRUDA (400 mg intravenously [IV] every six weeks) for up to 9 cycles (54 weeks) until disease recurrence or unacceptable toxicity (n=921), or; KEYTRUDA (400 mg IV every six weeks) plus oral placebo for up to 9 cycles (54 weeks) until disease recurrence or unacceptable toxicity (n=920). The major efficacy outcome measure was investigator-assessed DFS and an additional outcome measure was OS.

The safety of WELIREG in combination with KEYTRUDA was evaluated in LITESPARK-022. A total of 915 patients received WELIREG in combination with KEYTRUDA and a total of 913 patients received oral placebo in combination with KEYTRUDA. The median duration of exposure to WELIREG was 12.4 months (range 1 day to 20.1 months).