Researchers at Tennessee Oncology contributed to a global Phase III clinical trial that revealed an investigational targeted therapy extended overall survival compared with currently approved treatments for patients with previously treated KRAS G12C-mutated non-small cell lung cancer. The findings, presented at the 2026 European Society for Medical Oncology Congress and published in The New England Journal of Medicine, add to the evidence supporting a potential new treatment option for this difficult-to-treat form of lung cancer. The study evaluated divarasib, a next-generation therapy, against currently approved KRAS G12C inhibitors sotorasib and adagrasib.

Dr. Wade Iams, a medical oncologist and researcher at Tennessee Oncology’s Greco-Hainsworth Centers for Research, served as a principal investigator for the Phase III Krascendo 1 clinical trial. Genentech, a member of the Roche Group, sponsored the trial, which marks the first and only global head-to-head study to evaluate a next-generation KRAS G12C inhibitor versus approved first-generation KRAS G12C inhibitors. Tennessee Oncology operates one of the most active community-based clinical trial programs in the country, giving patients access to lung cancer research studies close to home. The practice is a founding member of OneOncology, the physician-led national partnership for independent medical practices, and participates in the OneOncology Research Network.

Dramatic Reduction in Death Risk and Disease Progression

The Krascendo 1 study found that patients treated with investigational divarasib had a 42% lower risk of disease progression or death compared with those receiving the first-generation therapies. More significantly, divarasib demonstrated a 44% lower risk of overall death compared with patients receiving sotorasib or adagrasib. These results represent a substantial improvement in outcomes for patients battling this challenging form of lung cancer, which has historically proven difficult to treat with conventional approaches.

Median overall survival reached 17.7 months with divarasib, a marked increase compared with 12.0 months for patients receiving sotorasib or adagrasib. The study also showed longer progression-free survival with the investigational therapy, meaning patients experienced more time before their cancer worsened. Furthermore, divarasib achieved nearly twice the objective response rate, indicating a significantly higher proportion of patients experienced measurable tumor shrinkage or disappearance. These combined findings paint a compelling picture of divarasib’s potential to transform treatment standards for this patient population.

Practice-Changing Potential for Lung Cancer Treatment

The study authors characterized the findings as having practice-changing potential for patients with previously treated KRAS G12C-mutated non-small cell lung cancer. This assessment reflects the magnitude of improvement observed in the trial, where divarasib outperformed currently approved therapies across multiple clinical endpoints. For oncologists treating NSCLC patients with KRAS G12C mutations, these results may reshape treatment algorithms and provide a more effective option for patients who have already undergone previous therapy lines. The head-to-head comparison design adds particular weight to the findings, as it directly demonstrates superiority over existing standards rather than relying on indirect comparisons or historical controls.

KRAS G12C mutations occur in approximately 13% of non-small cell lung cancer cases in the United States, making targeted therapies for this specific genetic alteration clinically significant for a substantial patient population. Until recently, KRAS mutations were considered “undruggable” targets, with no direct inhibitors available. The development of first-generation KRAS G12C inhibitors represented a breakthrough, but the Krascendo 1 results suggest that next-generation compounds may offer even greater clinical benefit. This progression from undruggable target to first-generation therapy to improved second-generation treatment illustrates the rapid evolution occurring in precision oncology.

Community-Based Research Advances Cancer Care

“Clinical research is not something that should be conducted only at major academic medical centers. When researchers conduct trials in community practices, we bring promising treatments to patients where they live,” said Dr. Iams.

Tennessee Oncology’s role in this pivotal trial underscores the critical importance of community-based clinical research programs in advancing cancer care. By conducting trials in community settings, researchers expand access to cutting-edge therapies for patients who might otherwise face geographic or logistical barriers to participation in academic medical center studies. This approach also ensures that clinical trial populations more accurately reflect the diversity of real-world cancer patients, potentially improving the generalizability of study findings. Community oncology practices that maintain active research programs bridge the gap between academic discovery and widespread clinical implementation.

Next Steps for Divarasib Development

The presentation of Krascendo 1 results at ESMO Congress and simultaneous publication in The New England Journal of Medicine represent key milestones in divarasib’s development pathway. These high-profile forums signal the oncology community’s recognition of the study’s significance and potential impact on clinical practice. The next logical steps typically include regulatory submissions to agencies such as the U.S. Food and Drug Administration and the European Medicines Agency, seeking approval for divarasib as a treatment for KRAS G12C-mutated NSCLC in patients who have received prior therapy.

If approved, divarasib would join the growing arsenal of targeted therapies available for genetically defined subsets of lung cancer, further advancing the paradigm of precision medicine in oncology. The therapy’s superior performance in head-to-head comparison positions it as a potential new standard of care, likely to be incorporated into treatment guidelines for this patient population. For patients with KRAS G12C-mutated NSCLC, the availability of more effective treatment options translates directly into extended survival and potentially improved quality of life during treatment.

Broader Implications for Precision Oncology

The success of divarasib in the Krascendo 1 trial reflects broader trends in cancer treatment toward increasingly sophisticated molecular targeting strategies. As researchers identify specific genetic drivers of cancer and develop therapies to inhibit those drivers, outcomes continue to improve for patients whose tumors harbor actionable mutations. The evolution from first-generation to next-generation KRAS G12C inhibitors demonstrates the ongoing refinement of targeted therapies, with each iteration potentially offering improved efficacy, better tolerability, or both. This iterative development process, guided by rigorous clinical trials like Krascendo 1, drives continuous progress in cancer care.

Tennessee Oncology’s participation in this landmark study, through its Greco-Hainsworth Centers for Research, exemplifies how community oncology practices contribute meaningfully to the advancement of cancer treatment. By enrolling patients in well-designed clinical trials, these programs generate the evidence needed to establish new standards of care while simultaneously offering trial participants access to potentially superior therapies before they become widely available. The collaborative model represented by OneOncology and its research network facilitates this integration of clinical care and research across multiple community practice sites.

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