Genentech, a member of the Roche Group (SIX: RO, ROP; OTCQX: RHHBY), announced today pivotal results from the Phase III Krascendo 1 study, which demonstrated the superior efficacy of investigational divarasib, a next-generation KRAS G12C inhibitor, compared with current standard of care KRAS G12C inhibitors in people with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC). Participants treated with divarasib monotherapy lived significantly longer, lowering the risk of death by 44% compared with sotorasib or adagrasib (overall survival, OS, HR 0.56, [95% CI: 0.41-0.78], p=0.0005). Median OS for divarasib is currently approximately 18 months, compared to 12 months for the control arm (see table below). No new safety findings were observed with divarasib and the most common treatment-related adverse events (TRAEs) were mainly low grade and manageable. These data were presented as a late-breaking abstract during a Presidential Symposium at the 2026 European Society for Medical Oncology (ESMO) Congress and simultaneously published in The New England Journal of Medicine.

“The Phase III Krascendo 1 results demonstrate the potential for divarasib to become a new standard of care for people with previously treated KRAS G12C-mutated lung cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “The superior efficacy against the current standard of care demonstrated in this head-to-head trial reinforces divarasib’s best-in-class profile. We are working closely with health authorities to bring this new treatment option to the people who need it.”

The G12C mutation is one of the most common KRAS mutations, found in approximately one in eight people with NSCLC. Accumulating evidence suggests that people with NSCLC who have the KRAS G12C mutation may have poorer outcomes than those who have the unmutated KRAS gene (wild-type disease). Despite the approval of current, first-generation KRAS G12C-targeted treatments, there remains a significant unmet need for more effective therapy options.

“New life-extending treatments are greatly needed, as most patients with this type of cancer will eventually relapse after initial therapy, and there are limited effective treatments for recurrent disease,” said study lead author Ferdinandos Skoulidis, M.D., Ph.D., professor of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center. “The Krascendo 1 results highlight divarasib’s practice-changing potential, as the first KRAS inhibitor to meaningfully improve overall survival for people with previously treated KRAS G12C-mutated lung cancer, compared with current treatment options.”

The Krascendo 1 study is the only global head-to-head study to evaluate a next-generation KRAS G12C inhibitor versus approved first-generation KRAS G12C inhibitors. The study met primary and key secondary endpoints, and divarasib demonstrated statistically significant and clinically meaningful improvements in OS and progression-free survival (PFS) over sotorasib or adagrasib. In addition to the OS benefit, divarasib reduced the risk of disease progression or death by 42% (PFS HR 0.58, [95% CI: 0.44-0.76], p<0.0001). The OS and PFS benefit was consistent across clinically relevant subgroups, and was observed regardless of PD-L1 expression or KEAP1 mutation status. The objective response rate (ORR) with divarasib was nearly double that of sotorasib or adagrasib.

Key efficacy results from the Phase III Krascendo 1 study:

Primary and key

secondary

endpoints

Divarasib arm

(n=167)*

Control arm

(adagrasib, sotorasib)

(n=171)*

Hazard Ratio /

(95% CI)

p-value

Median OS (months)

17.7

12.0

HR 0.56 (0.41-0.78)

p=0.0005

Median PFS (months)

9.8

5.7

HR 0.58 (0.44-0.76)

p<0.0001

12-month PFS rate (%)

44%

24%

–

–

Confirmed ORR (%)*

58%

32%

–

–

Median DOR (months)*

11.9

6.9

–

–

*Assessed in response-evaluable population (n=328; ten patients [divarasib arm, n=6; control arm, n=4] did not have measurable disease at baseline and were excluded from the response-evaluable set). Duration of Response (DOR) evaluated in those who responded to treatment (divarasib arm, n=94; control arm, n=54).

The safety profile of divarasib monotherapy was consistent with the known class effects of KRAS G12C inhibitors. The most common TRAEs comprised GI toxicity (most commonly, diarrhea, nausea, and vomiting) and hepatotoxicity. Fewer participants discontinued treatment due to TRAEs with divarasib (4.8% versus 11.7%) and the rate of serious TRAEs was approximately half that of sotorasib or adagrasib (7.8% versus 15.2% respectively), despite patients remaining on treatment for more than twice as long (11.3 months compared with 5.0 months).

Genentech is advancing a comprehensive Phase III clinical development program in NSCLC, investigating divarasib as both a monotherapy and as a chemotherapy-free combination, across different disease settings and lines of therapy. The U.S. Food and Drug Administration granted Breakthrough Therapy Designation to divarasib in 2022, and in 2026, Orphan Drug Designation for KRAS G12C-mutated NSCLC.

About Krascendo 1

The Krascendo 1 study [NCT06497556] is the only global head-to-head study evaluating a Kirsten rat sarcoma virus (KRAS) G12C inhibitor in direct comparison with first-generation approved KRAS G12C inhibitors. This Phase III, randomized, open-label, multicenter study evaluates the efficacy and safety of divarasib monotherapy versus sotorasib or adagrasib in people with previously treated KRAS G12C-mutated advanced or metastatic non-small cell lung cancer. The study includes 338 adults, randomized to receive either divarasib once daily (n=167) or, either sotorasib once daily or adagrasib twice daily (n=171). The primary endpoint is blinded independent central review (BICR)-assessed progression-free survival. Secondary endpoint measures include overall survival, confirmed objective response, duration of response, as well as other efficacy and safety measures.

About divarasib

Divarasib is an investigational, best-in-class, next-generation, oral, KRAS G12C inhibitor, discovered and developed by researchers within Roche and Genentech. It has shown greater potency and selectivity in preclinical studies compared with first-generation KRAS G12C-targeting treatments, sotorasib or adagrasib, with superior efficacy demonstrated in people with previously treated KRAS G12C-mutated NSCLC. Divarasib is designed to selectively bind to the KRAS G12C protein, locking the protein in an inactive (off) state, thereby turning off its tumor-driving signaling.

Divarasib’s comprehensive clinical development program is anchored by three Phase III studies:

Study

Intervention

Patient population

Krascendo 1

[NCT06497556]

Divarasib monotherapy vs sotorasib or adagrasib

Previously treated KRAS G12C-mutated advanced or metastatic NSCLC (second-line)

Krascendo 2

[NCT06793215]

Divarasib plus pembrolizumab

(chemotherapy-free combination) vs chemotherapy plus pembrolizumab

Previously untreated KRAS G12C-mutated advanced NSCLC (first-line)

Krascendo 3

[NCT07541170]

Adjuvant divarasib monotherapy vs immunotherapy or observation

Resected stage II–IIIB KRAS G12C-mutated NSCLC after standard of care chemoimmunotherapy (early-stage)

Divarasib underpins Genentech’s diversified pipeline targeting the RAS signaling pathway, including other mutant-selective inhibitors and a pan-RAS inhibitor, designed to extend the benefits of RAS inhibition strategies to more patients.

About KRAS G12C-mutated non-small cell lung cancer

Despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths worldwide, surpassing the combined mortality rates of breast, prostate, and stomach cancers. Each year, it claims the lives of 1.8 million people, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. KRAS is one of the most frequently mutated genes in lung cancer, occurring in approximately 25% of newly diagnosed lung cancers, and is associated with poor prognosis for patients. The G12C mutation is one of the most common KRAS mutations, found in approximately 12-14% of NSCLC cases.

The KRAS gene produces the KRAS protein, which acts as a cellular control switch, cycling between an active (on) and inactive (off) state to regulate cell growth and proliferation, making it a critical target for new therapeutic strategies. The G12C mutation locks the KRAS protein in its active (on) state, leading to continuous, unregulated signaling for cell growth, driving tumor proliferation.

About Genentech in Lung Cancer

With a 30-year legacy across oncology, Genentech has been driving innovations in small cell and non-small cell lung cancers that have shaped the treatment paradigm for people living with lung cancer. We are leveraging precision medicine to tackle some of the hardest-to-treat diseases, driven by our passion to deliver functional, real-world care. We are committed to ensuring that innovative solutions reach patients wherever they receive their care, working in lockstep with the community to deliver on our goal to improve outcomes for as many people affected by lung cancer as possible.

About Genentech

Founded 50 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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