FDA Grants Breakthrough Therapy to Olomorasib in Lung Cancer Subset

The FDA granted Breakthrough Therapy designation to olomorasib plus Keytruda for unresectable advanced or metastatic NSCLC with a KRAS G12C mutation.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to olomorasib in combination with Keytruda (pembrolizumab) as a first-line treatment option for patients with unresectable advanced or metastatic non-small cell lung cancer with a KRAS G12C mutation and PD-L1 expression of at least 50%.

The development was announced in a news release issued by Eli Lilly and Company, the manufacturer of olomorasib.

Breakthrough Therapy designation, as explained by the FDA on its website, is a process that is designed to speed up the development and review of drugs that are intended to treat a serious condition and when preliminary evidence indicates that the drug may demonstrate substantial improvement over available therapy.

The Breakthrough Therapy designation, according to the news release, is based on results from the phase 1/2 LOXO-RAS-20001 clinical trial as well as the dose optimization portion of the phase 3 SUNRAY trial. The company stated that updated results from an integrated analysis of these studies is set to be presented at the 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer, held Sept. 6 to 9 in Barcelona.

"The Breakthrough Therapy designation recognizes the potential for olomorasib to be a meaningful treatment advance and highlights the continued unmet need for improved options for patients with KRAS G12C-mutant NSCLC, particularly in the first-line setting in combination with standard-of-care immunotherapy," said Dr. David Hyman, Lilly chief medical officer, in a statement in the news release. "We look forward to presenting updated data from the olomorasib development program in significantly more patients and with longer follow-up at WCLC and continuing to investigate olomorasib in combination with immunotherapy-based regimens in a variety of treatment settings across the phase 3 SUNRAY-01 and SUNRAY-02 studies."

LOXO-RAS-2000` is an open-label, multicenter clinical trial evaluating the safety, tolerability and preliminary effectiveness of olomorasib among patients with KRAS G12c-mutant advanced solid tumors. According to its listing on clinicaltrials.gov, it is still recruiting participants, and is estimated to be completed in April 2027.

Findings from the trial presented at the 2024 ASCO Breakthrough Conference showed that, in efficacy-evaluable patients with metastatic disease being treated in the first line (17 patients), 77% of patients partially responded to treatment, meaning their disease shrunk but did not disappear. At a median follow-up of 5.5 months, the estimated six- and 12-month progression-free survival rates were both 72.8%, meaning that many patients lived without their disease spreading or worsening.

“Olomorasib in combination with pembrolizumab demonstrates promising antitumor activity,” lead study author Dr. Yutaka Fujiwara, chief of the Department of Thoracic Oncology at Aichi Cancer Center Hospital in Aichi, Japan, stated in an oral presentation of the data.

SUNRAY-01 is a double-blind study evaluating the effectiveness and safety of olomorasib administered in combination with Keytruda with or without chemotherapy as a first-line treatment for patients with KRAS G12C-mutant metastatic non-small cell lung cancer. According to its listing on clinicaltrials.gov, it is still recruiting participants, and is estimated to have primary completion in May 2029, followed by study completion in February 2032.

Olomorasib, as defined by the National Cancer Center on its website, is an orally available inhibitor of the oncogenic KRAS substitution mutation, G12C, with potential antineoplastic activity. The drug, the National Cancer Institute explained, selectively targets the KRAS G12C mutation and inhibits KRAS G12C mutant-dependent cell signaling; KRAS mutations may lead to tumor cell growth, proliferation, invasion, and metastasis.

References

1. “Lilly's olomorasib receives U.S. FDA's Breakthrough Therapy designation for the treatment of certain newly diagnosed metastatic KRAS G12C-mutant lung cancers,” news release, Sept. 4, 2025; https://investor.lilly.com/news-releases/news-release-details/lillys-olomorasib-receives-us-fdas-breakthrough-therapy
2. “Breakthrough Therapy,” FDA; https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy
3. “Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C);” https://clinicaltrials.gov/study/NCT04956640
4. “Olomorasib, Keytruda Combo Is Safe for Lung Cancer Subset,” CURE, April 13, 2024; https://www.curetoday.com/view/olomorasib-keytruda-combo-is-safe-for-lung-cancer-subset
5. “Study of Olomorasib (LY3537982) in Combination With Standard of Care in Participants With Resected or Unresectable KRAS G12C-mutant Non-Small Cell Lung Cancer (SUNRAY-02);” https://clinicaltrials.gov/study/NCT06890598
6. “olomorasib;” https://www.cancer.gov/publications/dictionaries/cancer-drug/def/olomorasib

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