Roche Reports Phase 3 Data Showing Divarasib Outperforms Amgen and BMS KRAS Inhibitors in Lung Cancer

Although Roche entered the KRAS G12C inhibitor race later than its rivals, it has pitted its candidate against Amgen’s and Bristol Myers Squibb’s approved therapies and now asserts that its next‑generation molecule offers superior performance.

In early Phase 3 results, Roche announced that divarasib achieved both primary and secondary endpoints with clinically meaningful and statistically significant improvement, noting no new safety concerns. The company said full data will be shared at an upcoming medical meeting and filed with regulators, aiming to make this treatment available to patients with KRAS G12C‑mutated non‑small cell lung cancer as quickly as possible.

The RAS gene family encodes proteins that function as molecular on/off switches governing cell proliferation. KRAS ranks among the most commonly altered members of this family; mutations that lock KRAS in an active state drive uncontrolled cell growth and tumorigenesis. Although the oncogenic role of mutant KRAS is well established, the protein has historically resisted therapeutic targeting.

Divarasib, Roche’s oral small‑molecule inhibitor, targets the KRAS G12C mutation, which occurs in roughly 14 % of non‑small cell lung cancers. By binding KRAS G12C and stabilizing its inactive conformation, the drug blocks the aberrant signaling that fuels tumor growth—an mechanism shared by Amgen’s Lumakras (the first FDA‑approved KRAS inhibitor for NSCLC, cleared in 2021) and Bristol Myers Squibb’s Krazati (approved in 2022).

Roche positions divarasib as a next‑generation KRAS G12C inhibitor with enhanced potency and selectivity relative to the Amgen and BMS agents. The preliminary findings stem from an open‑label Phase 3 trial that enrolled 338 adults harboring KRAS G12C‑positive NSCLC who had experienced disease progression after one to three prior systemic therapies. Participants were randomized to receive Roche’s once‑daily divarasib, Amgen’s once‑daily Lumakras, or Bristol Myers Squibb’s twice‑daily Krazati.

The study’s primary endpoint is progression‑free survival, with secondary assessments covering overall survival, confirmed objective response rate, and duration of response. Although detailed data have not yet been disclosed, Roche executives assert that divarasib demonstrates an advantage over the competing Amgen and BMS therapies.

“The superior survival observed in this global head‑to‑head trial of KRAS G12C inhibitors underscores divarasib’s potential to improve clinical outcomes for patients with KRAS G12C‑mutated non‑small cell lung cancer,” said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development, in a prepared statement. “These findings position divarasib as a new standard of care for previously treated lung‑cancer patients harboring this genetically defined alteration.”

Two additional Phase 3 studies are underway: one evaluates divarasib in combination with Merck’s Keytruda as a first‑line NSCLC therapy, while the other investigates the agent as an adjuvant treatment intended to prevent recurrence after surgical resection.

Roche is not alone in pursuing next‑generation KRAS G12C inhibition. Compounds aimed at locking the protein in the inactive state include glecirasib (Jacobio Pharma), olomorasib (Eli Lilly), and calderasib (Merck). Meanwhile, Revolution Medicines—known for its investigational pancreatic‑cancer RAS inhibitor daraxonrasib—is advancing an early‑stage KRAS G12C “on‑state” inhibitor named elironrasib.

BridgeBio Oncology Therapeutics, which describes itself as “best‑in‑RAS,” is developing BBO‑8520 to inhibit KRAS G12C in both active and inactive conformations. A Phase 1a/1b trial is currently enrolling NSCLC patients.

Photo by Roche

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