On October 1, 2026 Trethera Corporation ("Trethera"), a clinical stage biopharmaceutical company developing first-in-class therapies for cancer and autoimmune diseases, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for TRE-515 in combination with KRAS inhibitors for the treatment of G12C mutation-positive non-small cell lung cancer (NSCLC) previously treated with an anti-PD-(L)1 antibody and platinum-based chemotherapy.
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Lung cancer remains the leading cause of cancer-related mortality worldwide, with more than 2.5 million new cases and 1.8 million deaths globally. NSCLC accounts for approximately 80% of lung cancer deaths. While KRAS inhibitors (KRASi) have created a major advance for patients whose tumors harbor KRAS G12C mutations, response rates remain limited and many responding patients later experience relapse.
"Fast Track designation in lung cancer represents an important milestone for TRE-515 and further validates our strategy of combining dCK inhibition with targeted cancer therapies," said Dr. Ken Schultz, Trethera Chairman and CEO. "KRAS G12C inhibitors have transformed the NSCLC treatment landscape, but resistance and incomplete responses remain major challenges. We believe TRE-515 has the potential to address a key metabolic escape pathway used by cancer cells and improve outcomes for patients with this devastating disease."
TRE-515 inhibits deoxycytidine kinase (dCK), the key enzyme in the nucleoside salvage pathway, which can become activated and essential for abnormal cell growth in cancer. TRE-515 has demonstrated favorable safety and antitumor activity in an ongoing first-in-human trial. Trethera’s approach is based on the observation that KRASi-treated tumors may increase reliance on the salvage pathway as a metabolic support system under therapeutic stress. In preclinical studies, specialized PET imaging showed persistent dCK activity following KRASi treatment, while subsequent TRE-515 treatment completely blocked tumor dCK activity, providing a visual demonstration of the biological rationale for the drug combination (Figure 1).
"For decades, oncology has focused heavily on targeting oncogenic signaling pathways, including KRAS," said Dr. Owen Witte, UCLA Professor and Trethera co-founder. "The next frontier is understanding how cancer cells adapt metabolically to survive those therapies. If successful, TRE-515 could represent a first-in-class approach by targeting the nucleoside salvage pathway, a key metabolic support system that tumors may use under therapeutic stress."
The FDA Fast Track decision builds on Trethera’s $2.7 million NIH grant awarded in 2025 to evaluate TRE-515 with KRASi therapies and marks the second FDA Fast Track designation, following its prior designation in metastatic castration-resistant prostate cancer. Fast Track status is intended to facilitate development and expedite review for drugs addressing serious conditions with unmet medical need, including potential eligibility for more frequent FDA communication, Accelerated Approval, and Priority Review if relevant criteria are met.
"For patients with advanced NSCLC, the central challenge is not only achieving an initial response but also making that response more durable," said Dr. Evan Abt, UCLA Assistant Professor and co-investigator for the preclinical studies. "This Fast Track designation underscores the importance of rapidly evaluating innovative, rational combination strategies that may extend the benefit of KRAS-targeted therapies to more patients."
(Press release, Trethera, OCT 1, 2026, View Source [SID1234671234])