Roche's KRAS drug tops its rivals in lung cancer trial
Roche's chief medical officer, Levi Garraway.
Roche has thrown down the gauntlet to Amgen and Bristol Myers Squibb with new phase 3 data for its experimental KRAS G12C inhibitor, divarasib, which it says shows improved efficacy over their already approved therapies.
The Krascendo 1 study pitted divarasib directly against Amgen's Lumakras (sotorasib) and BMS's Krazati (adagrasib) in patients with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC) and, according to Roche, it was better at delaying disease progression and extending survival.
The results demonstrate "best-in-class potential" for divarasib in this type of lung cancer, said the Swiss pharma group, and will form the basis of regulatory filings.
While the full results will not be revealed until they are presented at a future cancer congress, Roche said that divarasib monotherapy achieved a statistically significant improvement in progression-free survival (PFS) compared to Lumakras and Krazati, the study's primary endpoint, with an equivalent safety profile.
Moreover, its new KRAS inhibitor also demonstrated a statistically significant improvement in overall survival in the study, which involved a "poor-prognosis patient population."
Roche is also running the Krascendo 2 trial of divarasib plus MSD's PD-1 inhibitor Keytruda (pembrolizumab) in first-line KRAS G12C-mutant NSCLC, and Krascendo 3, which is looking at adjuvant use of the drug in earlier-stage disease.
"The superior survival demonstrated in this global head-to-head comparison of KRAS G12C inhibitors confirms the potential of divarasib to improve clinical outcomes for people with KRAS G12C non-small cell lung cancer,” said Levi Garraway, Roche’s chief medical officer.
"These results should establish divarasib as a new standard of care for previously-treated lung cancer patients with this genetically defined tumour subtype."
Lumakras and Krazati were the first KRAS-targeted drugs to reach the market, after decades of research into what was once considered an "undruggable" target, but have so far failed to match that scientific achievement commercially, with sales staying fairly modest.
Initially tipped as having multibillion-dollar sales potential, they have been held back by narrow patient populations, problems with drug resistance, reimbursement hurdles and, at least in the beginning, limited access to KRAS testing. First-to-market Lumakras made sales of $367 million last year, with single-digit growth, while Krazati brought in $205 million, a rise of 62%.
Divarasib is one of several 'second-generation' KRAS inhibitors hoping to capture market share and grow the market for the class, along with MSD's calderasib and Eli Lilly's olomorasib, which are also in phase 3, and a growing list of earlier-stage candidates – including KRAS G12C, KRAS G12D, and pan-KRAS/RAS-targeting drugs – coming through the industry pipeline.
