Merck & Co. Inc. (NYSE:MRK) and Eisai on Tuesday announced results from the Phase 3 LITESPARK-012 trial of combination drugs for advanced clear cell renal cell carcinoma (RCC).

Clear cell RCC is the most common form of kidney cancer, accounting for roughly 75–80% of cases.

Triplet Regimen Misses Primary Endpoints

The trial evaluated the triplet therapy of Keytruda (pembrolizumab) plus Lenvima (lenvatinib) plus Welireg (belzutifan).

The study also evaluated MK-1308A, the coformulation of Keytruda and quavonlimab plus Lenvima.

Both combination regimens were compared to Keytruda plus Lenvima.

At a pre-specified interim analysis, the combination regimens did not meet the dual primary endpoints of progression-free survival (PFS) and overall survival (OS).

The safety profiles of the combination regimens were consistent with those observed in previously reported studies.

A full evaluation of the data from this study is ongoing, and Merck and Eisai will work with investigators to share the results.

Results from the LITESPARK-012 trial do not affect other ongoing trials from the LITESPARK clinical program, including those conducted jointly with Eisai.

As previously announced, the U.S. Food and Drug Administration (FDA) has accepted two supplemental New Drug Applications (sNDA) for review based on the Phase 3 LITESPARK-011 trial evaluating Welireg in combination with Lenvima for certain previously treated patients with advanced RCC and has set a Prescription Drug User Fee Act (PDUFA), or target action, date of October 4.

Analyst Sees Potential Opening For Alternative Strategy

William Blair, in an investor note on Tuesday, said, “While no numerical results were disclosed, we surmise the setback from the Keytruda-Lenvima-Welireg combination could theoretically open a path for a zanzalintinib-based HIF-2 alpha-based triplet regimen in the frontline RCC setting, if the efficacy benefits were close to meeting statistical significance.”

Merck is currently conducting the Phase 3 LITESPARK-033 study, which assesses zanzalintinib plus Welireg in frontline RCC patients who had previously been treated with Keytruda in the adjuvant setting. Zanzalintinib (XL092) is an investigational, oral, multi-targeted tyrosine kinase inhibitor (TKI) developed by Exelixis Inc. (NASDAQ:EXEL).

FDA Approves New HIV Treatment

On Tuesday, the U.S. Food and Drug Administration (FDA) approved Merck’s Idvynso (doravirine and islatravir) to treat HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine.

MRK Stock Price Activity: Merck shares were down 4.08% at $112.34 at the time of publication on Tuesday, according to Benzinga Pro data.

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