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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An experimental lung cancer drug from Akeso and Summit Therapeutics reduced the risk of death by 34% in a closely watched late-stage trial. The company released results on Sunday ahead of a presentation at the American Society of Clinical Oncology’s annual meeting. When combined with chemotherapy, the drug kept people with squamous non-small-cell lung cancer alive for a median of four months longer than the standard combination of immunotherapy and chemotherapy.

Researchers conducted the Phase 3 trial in China. They are currently running a global Phase 3 study. The result was statistically significant, according to an abstract released Sunday. The trial focused on a difficult-to-treat patient population, making the survival improvement particularly noteworthy.

“The fact that it shows an improvement in overall survival in a difficult-to-treat patient population is very encouraging,” said Dr. Suresh Ramalingam, executive director of the Winship Cancer Institute of Emory University. “I’m mindful of the fact that this trial was done exclusively in China, and that brings up the question of how do these data apply to patient populations outside of China, and that will require future investigations.”

How Ivonescimab Works Differently

The drug, called ivonescimab, is a bispecific antibody that targets two distinct proteins. It targets PD-1, similar to Merck’s best-selling drug Keytruda. It also targets VEGF, similar to Roche’s Avastin. PD-1 is a protein that helps cancer cells hide from the immune system. VEGF is a protein that promotes the growth of new blood vessels and can help cancer cells thrive.

The drug has become the subject of intense debate in the oncology and investment communities. Some experts say ivonescimab and similar drugs could be a successor to Merck’s wildly successful cancer drug Keytruda. Others warn it’ll disappoint like other once-promising ideas such as drugs targeting TIGIT, an immune receptor.

Market Reaction and Investor Concerns

The dueling narratives are reflected in the stock price of U.S.-based Summit Therapeutics. The company licensed the rights to ivonescimab outside of China from Akeso. Shares of Summit have skyrocketed nearly 600% in the two years since significant trial results emerged. Summit announced that ivonescimab more effectively controlled tumors than Keytruda in a separate China trial.

The stock has slid in the past month over concerns the drug won’t be as effective in a global population. Investors remain cautious about whether results from Chinese patients will translate to diverse populations worldwide. This geographic limitation creates uncertainty about regulatory approval in Western markets.

Why Overall Survival Matters

Previous studies showed ivonescimab can effectively control tumors. This endpoint is known as progression-free survival. That’s typically not enough to seek approval from the U.S. Food and Drug Administration. The FDA wants proof that cancer drugs can keep people alive longer. Older VEGF drugs that effectively controlled tumors struggled to improve survival rates.

The current results are particularly significant because they demonstrate an overall survival benefit, not just tumor control. The 34% reduction in death risk meets the FDA’s gold standard for cancer drug approval. This distinction separates ivonescimab from previous treatments that showed promise but failed to extend patient lives.

Global Trial Will Determine Future

The ongoing global Phase 3 study is crucial for regulatory approval outside China. It will provide results from diverse patient populations. This addresses concerns about geographic limitations. If ivonescimab demonstrates similar efficacy globally, it could transform lung cancer treatment.

The global study tests whether the drug’s performance in Chinese patients translates to other ethnic groups and healthcare settings. Genetic differences, environmental factors, and treatment practices vary significantly between regions. These variables can affect drug efficacy and safety profiles. Regulators in the United States and Europe will scrutinize the global trial data carefully.

Implications for Cancer Treatment Landscape

Ivonescimab’s dual-targeting approach represents a new generation of cancer immunotherapy. Traditional treatments like Keytruda focus on a single pathway. By targeting both PD-1 and VEGF simultaneously, the bispecific antibody attacks cancer through multiple mechanisms. This strategy could overcome resistance that develops with single-target therapies.

Squamous non-small-cell lung cancer remains one of the deadliest cancer types. Patients have limited treatment options after first-line therapy fails. The four-month survival improvement, while modest, represents meaningful additional time for patients and families. Any extension of life in this aggressive cancer type is considered clinically significant.

The pharmaceutical industry watches these developments closely. Keytruda generates over $25 billion in annual revenue for Merck. A successor drug that improves upon Keytruda’s efficacy could capture substantial market share. However, pricing, manufacturing capabilities, and patent protections will all influence commercial success.

Next Steps and Timeline

Researchers will present full trial data at the upcoming American Society of Clinical Oncology meeting. The detailed results will reveal important safety information and subgroup analyses. Oncologists want to know which patient populations benefit most from the treatment. They also need data on side effects and quality of life measures.

Summit Therapeutics and Akeso must complete their global trial before seeking regulatory approval. The timeline for approval in Western markets remains uncertain. Even with positive results, the approval process typically takes several years. The companies face competition from other experimental treatments in development.

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