Novartis' targeted cancer drug combo goes tumor-agnostic with new FDA approval

After melanoma, lung cancer and thyroid cancer, Novartis’ Tafinlar-Mekinist combination can now be used to treat any tumors regardless of their location as long as they bear a specific biomarker.

Wednesday, Novartis said the FDA has granted an accelerated approval to the pairing of Tafinlar and Mekinist for any advanced solid tumors with the BRAF V600E mutation. The patient must have progressed following prior therapy and have no alternative treatment options.

The tumor-agnostic nod gives the Novartis drugs an edge over competitor BRAF-MEK inhibitor duos, namely Pfizer’s Braftovi/Mektovi and Roche’s Zelboraf/Cotellic. The pan-tumor indication covers patients as young as 6 years old, making it the first for a BRAF-MEK inhibitor in pediatric patients.

“Physicians should consider a BRAF test as a routine diagnostic step that could enable a new option for treating patients with many solid tumors,” Vivek Subbiah, M.D., at the University of Texas MD Anderson Cancer Center, said in a statement.

BRAF-MEK inhibitors are best known as standard of care for BRAF-mutant melanoma. Over the years, the Tafinlar-Mekinist combo has added BRAF-mutant non-small cell lung cancer (NSCLC) and anaplastic thyroid cancer to its approved indications, and Pfizer’s Braftovi, used alongside Eli Lilly’s EGFR inhibitor Erbitux, expanded into BRAF-mutated colorectal cancer in 2020.

For the pan-tumor nod, Tafinlar and Mekinist showed tumor shrinkage benefits in several other cancer types in two clinical trials. Across 131 patients enrolled in the phase 2 ROAR study and Arm H of the NCI-MATCH trial, the Novartis combo triggered responses in biliary tract cancer, high-grade and low-grade glioma, ovarian cancer, small intestine adenocarcinoma and others.

Plus, in a small trial coded Study X2101, the doublet showed an acceptable safety profile and some tumor shrinkage ability in pediatric patients, mainly those with pretreated glioma.

BRAF V600E is the most common type of BRAF mutation, making up about 90% of all BRAF-mutant cancers. BRAF mutations have been identified in more than 20 tumor types.

Last year, Tafinlar and Mekinist reeled in $1.69 billion in sales, good for 8% growth at constant currencies. The increase was mainly driven by approvals in postsurgery adjuvant treatment of melanoma and metastatic NSCLC. The rival BRAF-MEK drugs are much smaller assets on the sales metric.

Wednesday's FDA accelerated approval means Novartis will need to offer verification of the combo’s benefit in a confirmatory trial. As Novartis noted, given the rarity of the mutation, it may be difficult to run phase 3 trials in some BRAF-driven tumor subtypes.

Novartis may already have confirmatory evidence for pediatric glioma patients, which could potentially also allow it to reach an even younger population. In children as young as 1, Tafinlar and Mekinist cut the risk of progression or death by 69% over chemotherapy when given as first systemic treatment for BRAF V600 pediatric low-grade glioma. Novartis presented the data from the phase 2/3 TADPOLE trial at the 2022 American Society of Clinical Oncology annual meeting earlier this month.

In a single-arm cohort of children with relapsed or refractory BRAF V600 high-grade gliomas, the Novartis combo showed a response rate of 56.1%.