What New KRAS Drug Data From ESMO 2026 Mean for Patients

For people with lung or pancreatic cancer driven by changes in the KRAS gene, research presented at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain, brought several updates on targeted drugs designed to block the protein that fuels these cancers.

KRAS and related RAS genes act like a switch for cell growth. When they are mutated, that switch can get stuck in the "on" position. One form, called KRAS G12C, is found in about 13% of people with non-small cell lung cancer (NSCLC), according to drugmaker Eli Lilly and Company, and more than 90% of pancreatic cancers have a mutation in a RAS gene, according to UCLA Health.

A newer drug outperformed approved options in lung cancer

In a phase 3 trial called Krascendo 1, an investigational pill called divarasib was compared with two approved drugs, Lumakras (sotorasib) and Krazati (adagrasib), in 338 people with NSCLC with a specific KRAS change called G12C whose cancer had grown after earlier treatment. The results were presented at the meeting's Presidential Symposium and published at the same time in The New England Journal of Medicine. The trial was sponsored by Roche and its subsidiary Genentech, which developed divarasib.

People taking divarasib went a median of 9.8 months before their cancer grew, compared with 5.7 months with the approved drugs, according to a Roche news release. They also lived longer: a median of 17.7 months, compared with 12 months. More than half (58%) saw their tumors shrink, compared with about a third (32%).

"For patients with KRAS G12C-mutant lung cancer, extending survival while delaying cancer progression are the outcomes that matter most," Dr. Ferdinandos Skoulidis, the study's lead author and a professor at The University of Texas MD Anderson Cancer Center in Houston, said in a news release from the cancer center.

Severe treatment-related side effects were less common with divarasib (about 25% vs. 35%), and fewer people stopped treatment because of side effects (about 5% vs. 12%), according to a summary of the findings published by ESMO. Liver problems were less frequent with divarasib, but severe diarrhea was more common (9% vs. 3%). Divarasib is not yet approved by the Food and Drug Administration (FDA).

Combining targeted therapy and immunotherapy earlier in treatment

Another investigational drug, olomorasib, is being studied as a first treatment for KRAS G12C lung cancer, combined with the immunotherapy Keytruda (pembrolizumab). Among 85 people who received the combination, 55% were alive without their cancer growing after 18 months, according to a news release from Lilly, which is developing the drug. When chemotherapy was added in a separate group of 77 people, tumors shrank in 62%. The findings, from early-phase studies and the safety lead-in of a phase 3 trial, were shared in two presentations at the meeting.

The FDA has already granted olomorasib a breakthrough therapy designation, which is meant to speed up its development. Lilly expects larger phase 3 results in the first half of 2027. The most common serious side effects with olomorasib and Keytruda were changes in liver blood tests and diarrhea, according to the company.

Pancreatic cancer: benefit across RAS changes

Rasonque (daraxonrasib), a daily pill approved by the FDA in August 2026 for metastatic pancreatic cancer that has already been treated, helped people live a median of 13.2 months, compared with 6.7 months with chemotherapy, in the RASolute 302 trial, which was published earlier this year in The New England Journal of Medicine. A new analysis presented at ESMO found that the benefit held across different types of RAS changes, including in people whose tumors had no identified RAS mutation, though some of those groups were small, according to a UCLA Health news release.

"In this analysis, we demonstrate that depending on the individual mutation, daraxonrasib may have a different response," Dr. Zev Wainberg, a professor of medicine at UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, who presented the findings, said in the release.

Early research is also testing drugs aimed at a different change, KRAS G12D, which appears in about 40% of pancreatic cancers, according to drugmaker Incyte. In a small early study of 54 people, Incyte's investigational drug INCB161734, given with standard chemotherapy, shrank tumors in many patients, the company reported. Diarrhea and nausea were common, though mostly mild to moderate. A larger trial is underway.

What patients and caregivers should know

• Ask about biomarker testing. These drugs only work against specific gene changes, so knowing whether a tumor has a KRAS or other RAS mutation, and which one, can open treatment and clinical trial options.
• Ask about clinical trials. Several of these drugs are available only through studies right now, including trials testing them earlier in treatment.
• Know the side effects to watch for. Diarrhea, nausea and changes in liver blood tests were common across these drugs. Tell the care team about new or worsening symptoms, and keep up with scheduled blood work.
• Results are averages. A median shows the midpoint across a group, and individual results vary. Talk with the care team about what these findings mean for a specific situation.

References

1. New data on Lilly’s investigational treatment olomorasib at ESMO 2026 show durable first-line activity in KRAS G12C-mutant non-small cell lung cancer. News release. Eli Lilly and Company. October 25, 2026. Accessed October 26, 2026. https://www.prnewswire.com/news-releases/new-data-on-lillys-investigational-treatment-olomorasib-at…
2. ESMO: new analysis reinforces survival benefits of targeted therapy for advanced pancreatic cancer. News release. UCLA Health. October 23, 2026. Accessed October 26, 2026. ESMO: New analysis reinforces survival benefits of targeted therapy for advanced pancreatic cancer
3. Skoulidis F, et al. Krascendo 1: efficacy and safety of divarasib vs sotorasib or adagrasib in previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC. N Engl J Med. Published online October 25, 2026. doi:10.1056/NEJMoa2605703
4. Roche’s divarasib demonstrated best-in-class efficacy, advancing the standard of care in previously treated KRAS G12C-mutated lung cancer. News release. Roche. October 25, 2026. Accessed October 26, 2026. Roche’s divarasib demonstrated best-in-class efficacy, advancing the standard of care in previously …
5. ESMO 2026: new targeted therapy improved survival for patients with KRAS-mutated lung cancer. News release. The University of Texas MD Anderson Cancer Center. October 25, 2026. Accessed October 26, 2026. https://www.mdanderson.org/newsroom/research-newsroom/esmo-2026--new-targeted-therapy-improved-surv…
6. Divarasib outperforms approved KRAS G12C inhibitors in NSCLC. European Society for Medical Oncology. October 25, 2026. Accessed October 26, 2026. https://www.esmo.org/insights-by-esmo/all-news/divarasib-outperforms-approved-kras-g12c-inhibitors-…
7. FDA grants breakthrough therapy to olomorasib in lung cancer subset. CURE. Accessed October 26, 2026. FDA Grants Breakthrough Therapy to Olomorasib in Lung Cancer Subset | CURE
8. O’Reilly EM, Wainberg ZA, Hendifar AE, et al; RASolute 302 Trial Investigators. Daraxonrasib or chemotherapy in previously treated metastatic pancreatic cancer. N Engl J Med. Published online May 31, 2026. doi:10.1056/NEJMoa2605555
9. Incyte highlights new data advancing its gastrointestinal cancer portfolio at ESMO 2026. News release. Incyte. October 26, 2026. Accessed October 26, 2026. Incyte Highlights New Data Advancing its Gastrointestinal Cancer Portfolio at ESMO 2026

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