AACR: Roche's triple threat—Tecentriq, Cotellic and Zelboraf—stalls melanoma progression

Roche
Adding Roche's Tecentriq to its Cotellic and Zelboraf kept disease at bay longer for melanoma patients. (Roche)

Back in December, Roche unveiled a win for its cocktail of Tecentriq, Cotellic and Zelboraf in patients with BRAF V600-mutated melanoma. And details of that win are here.

In a phase 3 study presented virtually at the American Association for Cancer Research annual meeting, adding Tecentriq to the targeted melanoma drugs decreased the risk of disease progression or death by 22% versus the Cotellic and Zelboraf combo alone.

RELATED: Roche's Tecentriq rebounds in melanoma, notching 3-drug cocktail win with Cotellic and Zelboraf

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Patients on the triple combo went a median 15.1 months without their disease worsening, compared with 10.6 months for those who didn’t receive Tecentriq as part of their treatment.

All told, patients responded at a similar rate to both combos, investigators pointed out. But responses lasted longer for those those taking the trio, coming in at a median 21 months against 12.6 months for the Cotellic and Zelboraf pairing.

All subgroups—broken down by age, markers of disease burden and other factors—also favored the Tecentriq arm, Grant McArthur, head of the molecular oncology lab at the Peter MacCallum Cancer Centre in Melbourne, Australia, said during Monday morning's presentation.

"Patients with advanced BRAF mutant melanoma can be treated with combinations of BRAF and MEK inhibitors"—such as Cotellic and Zelboraf—"that offer the advantage of high response rates. However, unfortunately for many patients, these responses are short-lived. Immune checkpoint inhibitors, in contrast provide more durable responses but have a lower response rate," he said.

The scientific rationale for the study "was founded on the hypothesis that, with the Tecentriq combination, multiple steps in the cancer immunity cycle could be targeted and potentially result in improved outcomes for patients,” a spokesperson for Roche’s Genentech added by email.

While adding another drug to the mix can often amp up toxicity levels and spur more side effects, in the trial—called IMspire150—the rate of serious treatment-related side-effects was similar between the two groups, investigators noted. A higher percentage of patients—15.7%—actually stopped treatment on the two-drug combo than did on the three-drug combo (12.6%).

RELATED: ESMO: Roche's Tecentriq-Cotellic duo tried—and failed—to beat Merck's Keytruda in melanoma

With IMspire150, Roche is looking to bring Tecentriq into a disease area where top rivals from its PD-1/L1 class—Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo—have been contending for years.

But while “targeted treatments and immunotherapies have made much progress for melanoma patients” over the last decade, “patients with certain types of advanced melanoma, such as BRAF-mutation-positive, still have poor prognoses and more options are needed,” the Genentech spokesperson said.

Still, as Stifel analyst Stephen Willey wrote to clients late last year, an approval in the face of such stiff competition wouldn’t necessarily generate much in the way of additional sales. He called the trial "more of a ‘check the box’ vs. an ‘expand the market’ exercise.”

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