Ongoing phase 1 dose-escalation trial of KO-2806 (FIT-001) for the treatment of patients with KRASG12C-mutated non-small cell lung cancer expected to begin dosing patients in combination with adagrasib by mid-2024.
Kura Oncology, Inc., a clinical-stage biopharmaceutical company, and Mirati Therapeutics, Inc., a commercial-stage targeted oncology company, have announced a clinical collaboration and supply agreement to evaluate the combination of KO-2806, a next-generation farnesyl transferase inhibitor (FTI), and adagrasib, a highly selective KRASG12C inhibitor, in patients with KRASG12C-mutated non-small cell lung cancer (NSCLC).1
“Recent findings suggest that combining KO-2806 with adagrasib can drive tumor regressions and enhance both duration and depth of antitumor response in preclinical models of KRASG12C-mutated NSCLC,” said Stephen Dale, MD, chief medical officer, Kura Oncology, in a press release. “This collaboration highlights the potential to address the urgent need for more durable and effective treatment options for patients with advanced solid tumors, and we look forward to collaborating with Mirati, an established leader in targeted oncology.”1
On October 19, 2023, Kura Oncology announced that the first patient had been dosed in the FIT-001 phase 1 dose-escalation trial of KO-2806.
“Our understanding of how to use FTIs to target farnesylated proteins has matured significantly beyond our initial strategy to target HRAS mutant tumors. With the success of targeted therapies such as KRASG12C inhibitors, tyrosine kinase inhibitors and EGFR inhibitors, there is now considerable focus on the development of companion therapeutics that have potential to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance,” said Troy Wilson, PhD, JD, president and chief executive officer of Kura Oncology, in the October 19 press release.2
NSCLC is one of the two main types of lung cancer and comprises approximately 85% of all lung cancer cases. The slow growing disease often metastasizes and spreads to other parts of the body by the time it is diagnosed, making NSCLC more difficult to treat. The American Cancer Society estimates that for 2023, there will be approximately 238,340 new diagnoses of lung cancer, with 117,550 cases in men and 120,790 cases in women, with approximately 127,070 deaths from lung cancer, with 67,160 in men and 59,910 in women.3
According to the October 19 press release, FIT-001 is a phase 1, first-in-human, multicenter, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of KO-2806 when administered as monotherapy and in combination with targeted therapies.2
Kura Oncology had also announced its plans to evaluate KO-2806 in dose-escalation combination cohorts with other targeted therapies, beginning in KRASG12C-NSCLC and clear cell renal cell carcinoma (ccRCC).2
The phase 1 interventional study (Clinicaltrials.gov identifier NCT06026410) has an estimated enrollment of 270 and is currently recruiting. The estimated study completion date is March 2027.4
“We are pleased to collaborate with Kura Oncology on this clinical study of KO-2806 with adagrasib. Preclinical work demonstrates the ability of adagrasib, in combination with a FTI, to improve patient outcomes,” said Alan Sandler, MD, chief medical officer, Mirati Therapeutics in a press release. “This collaboration exemplifies the potential combinability of adagrasib as a key differentiation from other KRASG12C inhibitors.”1