Researchers at Tennessee Oncology have helped lead a global Phase III clinical trial showing that an experimental targeted medication called divarasib extended overall survival by nearly six months compared with standard targeted therapies in patients with a specific, difficult-to-treat form of lung cancer. Presented on Oct. 25, 2026, at the European Society for Medical Oncology (ESMO) Congress and published in The New England Journal of Medicine, the study evaluated adults with previously treated advanced or metastatic non-small cell lung cancer (NSCLC) carrying a genetic change known as a KRAS G12C mutation, according to AOL.com.

Wade Iams, MD, MSCI, a medical oncologist and researcher at Tennessee Oncology's Greco-Hainsworth Centers for Research in Nashville, served as a principal investigator for the study, known as the KRAScendo 1 trial. Sponsored by Genentech, a member of the Roche Group, the trial directly compared the next-generation experimental medication divarasib against two currently approved first-generation KRAS G12C inhibitors, sotorasib and adagrasib. For patients facing limited options after initial lung cancer treatments stop working, the findings point toward a potential new way to slow the disease and extend life.

How the Experimental Therapy Works

Non-small cell lung cancer is the most common form of lung cancer, and KRAS is one of the most frequently mutated genes driving its growth. When a specific error called the KRAS G12C mutation occurs, it produces an abnormal protein that acts like a stuck "on" switch, continually signaling cancer cells to divide and spread. Targeted therapies called KRAS G12C inhibitors are oral medications designed to attach to that mutated protein and lock it in an inactive state, slowing or stopping tumor growth without harming as many healthy cells as traditional chemotherapy.

First-generation drugs in this class—sotorasib and adagrasib—gave doctors their first targeted tools against this specific mutation. However, tumors often develop resistance over time, causing the cancer to begin growing again. According to KXAN, divarasib is a next-generation inhibitor engineered to bind more selectively to the mutated KRAS G12C protein. By locking onto the cancer-driving target with greater precision, researchers aim to shut down the tumor's growth signals more effectively and keep the disease under control for a longer period.

Key Survival Gains in the KRAScendo 1 Trial

To test whether this refined design translates into better outcomes for patients, the randomized, open-label, multicenter KRAScendo 1 trial enrolled 338 adults whose advanced or metastatic KRAS G12C-mutated lung cancer had progressed after prior treatment, according to an Associated Press press release pickup. Among the participants, 167 patients were randomly assigned to take divarasib once daily, while 171 patients were assigned to take either once-daily sotorasib or twice-daily adagrasib.

The head-to-head comparison showed clear differences in patient outcomes between the two groups:

  • Longer Overall Survival: Patients treated with divarasib lived a median of 17.7 months, compared with 12.0 months for those receiving sotorasib or adagrasib.
  • Lower Risk of Death: Treatment with divarasib was associated with a 44% lower relative risk of overall death compared with the first-generation drugs.
  • Delayed Disease Worsening: Patients in the divarasib group experienced a 42% lower risk of disease progression or death.
  • Higher Tumor Response: Divarasib produced longer progression-free survival and nearly twice the objective response rate—a measure of how many patients saw their tumors shrink significantly—compared with the older targeted therapies.

While the study authors and sponsors described KRAScendo 1 as the first and only global head-to-head trial comparing a next-generation KRAS G12C inhibitor against approved first-generation options, that superlative comes from company press announcements and has not been independently verified across all global trial registries. Additionally, while the announcements highlight substantial survival gains, the publicly released summaries do not include detailed statistical margins such as confidence intervals, p-values, exact response-rate percentages, or complete breakdowns of side effects. Independent oncology experts typically review the complete peer-reviewed data in The New England Journal of Medicine to evaluate how well patients tolerated the medication and how side effects compare across the different drugs.

The Role of Community Cancer Research

A vital element of the KRAScendo 1 study was where it took place. Rather than restricting the trial to large university hospitals, researchers enrolled patients through community-based practices like Tennessee Oncology. Tennessee Oncology is a founding practice of OneOncology, a national partnership of independent medical practices, and participates in the OneOncology Research Network.

Dr. Iams noted that offering advanced research in local clinics directly benefits both patients and medical science. "Clinical research is not something that should be conducted only at major academic medical centers," Dr. Iams said in the announcement. "When researchers conduct trials in community practices, we bring promising treatments directly to patients where they receive their care, while also enrolling a broader and more representative patient population. That diversity strengthens the science and helps us better understand how treatments will work in the real world. It also gives patients access to cutting-edge therapies without requiring them to travel long distances to participate in research."

What This Means for Patients and Families

For people living with advanced non-small cell lung cancer, these results reinforce the importance of comprehensive biomarker testing. Identifying whether a tumor carries a KRAS G12C mutation—typically done through a tissue biopsy or a blood-based liquid biopsy—helps oncologists match patients with targeted treatments tailored to their cancer's specific genetics.

At the same time, patients and caregivers should keep in mind that divarasib remains an investigational medication. At the time of the Oct. 25, 2026 announcement, it had not yet been approved by the U.S. Food and Drug Administration (FDA) or other regulatory authorities for routine clinical prescription outside of a clinical trial. Positive Phase III trial results are typically the final step before a drugmaker submits an application for regulatory review, a process that evaluates both safety and effectiveness before a medication becomes widely available.

Frequently Asked Questions

Can patients currently get a prescription for divarasib?

Not as a standard prescription. According to the trial announcements, divarasib is still an experimental therapy and has not yet received approval from the U.S. FDA or other global health regulators. Patients interested in next-generation targeted therapies should speak with their oncologist about whether they qualify for ongoing clinical trials or if approved medications like sotorasib or adagrasib are appropriate for their current treatment plan.

How did side effects and individual drug comparisons break down in the trial?

The initial press announcements reported that divarasib nearly doubled the tumor response rate and cut the risk of progression or death by 42%, but they did not release the exact percentages of patients who experienced side effects, treatment discontinuations, or how divarasib performed against sotorasib and adagrasib individually. Oncologists will rely on the full data set published in The New England Journal of Medicine to assess the medication's day-to-day safety profile.

What role did Tennessee Oncology play in the study?

Dr. Wade Iams of Tennessee Oncology's Greco-Hainsworth Centers for Research served as a principal investigator for the global Phase III trial. While the announcements did not specify the exact number of local patients or clinic sites involved, Tennessee Oncology provided community-based trial access so local patients could participate without traveling to distant university centers.

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