Array's Braftovi, Mektovi in combination with Erbitux improves survival in metastatic colorectal cancer study

Array BioPharma announced Tuesday that in a Phase III study, the pairing of the BRAF inhibitor Braftovi (encorafenib) and the MEK inhibitor Mektovi (binimetinib) in combination with Merck KGaA and Eli Lilly's Erbitux (cetuximab) in patients with BRAFV600E-mutant metastatic colorectal cancer, following one or two prior lines of therapy, met both primary endpoints of confirmed objective response rate (ORR) and overall survival (OS). Array said it plans to submit marketing applications based on data from the BEACON CRC trial in the second half of the year.  

In the study, 665 patients with BRAFV600E-mutant metastatic colorectal cancer were randomised to treatment with the three-drug combination of Braftovi, Mektovi and Erbitux or Erbitux in combination with irinotecan-containing regimens. In addition to the primary goals, the secondary endpoint analysis examined the combination of Braftovi and Mektovi in comparison with the control regimen of Erbitux plus irinotecan-containing regimens.  

Results from the interim analysis based on data from the first 331 randomised patients, showed that ORR for the triplet of Braftovi, Mektovi and Erbitux was 26.1 percent, versus 1.9 percent for Erbitux plus irinotecan-containing regimens. Meanwhile, data from all 665 patients in the trial demonstrated that the triple regimen reduced the risk of death by 48 percent versus control, with median OS in the two groups of 9 months and 5.4 months, respectively. Array added that for the secondary endpoint analysis, the combination of Braftovi and Erbitux demonstrated a significant improvement in ORR of 20.4 percent, while the risk of death was reduced by 40 percent versus control, with median OS of 8.4 months.  

Commenting on the results, Array CEO Ron Squarer said "this has the potential to be the first chemotherapy-free, targeted regimen for mCRC patients, a population with a very high unmet need for effective treatments."  The company is also investigating the combination as a first-line treatment for patients with colorectal cancer with the BRAF V600E mutation. "We've seen that in earlier lines of patients there appears to be more tumour shrinkage...the goal ultimately is to treat patients as early as possible," Squarer remarked.

In January, Array presented updated results from the Phase III BEACON study, showing that the median OS for the combination of Braftovi, Mektovi and Erbitux was 15.3 months in patients with BRAFV600E-mutant metastatic colorectal cancer. For related analysis, see ViewPoints: BEACON sets high hurdle for Array's Braftovi/Mektovi.

The combination of Braftovi and Mektovi is currently approved in a number of countries, including the US and EU, for the treatment of patients with BRAF-mutant metastatic melanoma.  Meanwhile, the combination of Braftovi, Mektovi and Erbitux has been granted FDA breakthrough therapy designation year for the treatment of BRAFV600E-mutant metastatic colorectal cancer. More recently, the National Comprehensive Cancer Network updated its guidelines to recommend the use of Braftovi and Mektovi together with Erbitux or Amgen's Vectibix (panitumumab) for use in patients with BRAFV600E-mutant metastatic colorectal cancer after the failure of one or two lines of therapy.  

Array has granted Ono Pharmaceutical rights to commercialise both Braftovi and Mektovi in Japan and South Korea, Medison to market the drugs in Israel and Pierre Fabre rights to commercialise them in all other countries, including Europe, Latin American and Asia.

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