Roche-owned Genentech’s KRAS G12C inhibitor, divarasib, has outperformed marketed drugs in its class in a Phase III head-to-head study – a result the company says could put the medicine in pole position in the KRAS G12C non-small cell lung cancer (NSCLC) market.
Genentech evaluated its next-generation KRAS G12C blocker in the late-stage Krascendo 1 study (NCT06497556), which pitted divarasib against two first generation alternatives: Amgen’s Lumykras (sotorasib) and Bristol Myers Squibb’s (BMS) Krazati (adagrasib).
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During the trial, which was comparing the drug’s efficacy and safety to Lumykras and Krazati in previously treated patients, divarasib significantly improved both progression-free survival (PFS) and overall survival (OS) among treated patients – meeting both its primary and key secondary endpoints, with the drug’s safety profile remaining consistent with prior studies.
While Genentech did not reveal specific safety details at this stage, the company did note that researchers observed no new safety findings, and most treatment-associated events were manageable and reversible.
Genentech said it would submit the data to health authorities and aims to bring the drug to KRAS G12C NSCLC patients “as soon as possible.”
Targeting KRAS in NSCLC
Divarasib achieves these results as KRAS remains one of the most common drivers of disease in metastatic NSCLC – presenting in around 14% of cases. Of these, around 40% are of the KRAS G12C variant, according to a paper published in Cancer Gene Therapy. Despite advancements in treatment spearheaded by the approvals of first-generation KRAS inhibitors like Lumykras and Krazati, the durability of response in NSCLC is often limited due to the tumour’s ability to rapidly build a resistance to treatment.
According to Levi Garraway, Roche’s CMO and head of global product development, the superior survival observed in the divarasib patient group confirms the drug’s potential to improve clinical outcomes, while potentially establishing the drug “as a new standard of care (SoC) for previously treated lung cancer patients with this genetically defined tumour subtype.”
Meanwhile, GlobalData oncology analyst, Biswajit Podder, noted that the move could “shift the later-line algorithm toward divarasib as the preferred targeted option after prior systemic therapy, rather than simply adding another alternative,”
“Commercially, it may put meaningful pressure on sotorasib or adagrasib. However, the press release lacks median PFS, OS, hazard ratios, CNS outcomes, subgroup data and detailed tolerability, so the magnitude of advantage remains unclear. If the full results are consistent, divarasib is likely to see broad later-line uptake,” Podder added.
In a research note, Jefferies analysts put the revenue opportunity from divarasib in second-line KRAS G12C NSCLC between SFr1-2bn, which they say is “50% reflected in consensus.” However, they believe that Roche’s studies on divarasib in the frontline KRAS G12C NSCLC setting will be most meaningful, despite the bar being higher.
Targeted and pan-RAS approaches battle it out
The emergence of pan-RAS agents like Revolution Medicines’ daraxonrasib in Phase III development, the analysts add, could also complicate the commercial picture for divarasib. “KRASCENDO-1 is a small win for Roche, but we view it as premature to claim overall victory,” they add.
In a previous podcast covering readouts from the 2026 American Society of Clinical Oncology (ASCO) conference, GlobalData analysts touted daraxonrasib as a game changer; researchers are currently evaluating the drug in the Phase III RASolve-301 trial for RAS-mutant NSCLC. Jefferies analysts argue that this trial will be the most important in determining whether the future belongs to “highly potent, mutation-specific agents like divarasib, or whether broader pan-RAS agents like daraxonrasib will be more successful.
