Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, occurring in approximately 80% of patients.1 Due to the asymptomatic nature of early disease, many patients are diagnosed with later stages of disease, and typically have short overall survival.2 In the United States, at initial diagnosis of NSCLC, approximately 55% of patients have distant metastases with a 5-year survival rate of 7%, despite the recent development of novel anti-cancer therapies and regimens.3

KRAS, a member of the RAS family, is a key regulator of signaling pathways that are responsible for cell proliferation, differentiation, and survival. KRAS oncogene is frequently mutated in human tumors and activating mutations in KRAS occur in 20-30% of NSCLC.

The evaluation of milciclib in combination with gemcitabine was suggested by preclinical studies as well a clinical trial conducted patients with refractory solid tumors. In the Phase I dose-escalation study 16 patients were treated with Milciclib at 3 dose levels and with a fixed dose of gemcitabine. Patients in this study were resistant to standard of care (SoC) therapy, and no other treatment options were available. Overall, the combination was well tolerated and showed encouraging clinical benefit with 1 partial remission and 10 patients with a disease stabilization including patients refractory to previous gemcitabine treatment. The partial remission was documented in a NSCLC patient with refractory treatment to gemcitabine. Based on these results Tiziana is exploring to conduct a study to evaluate the combination of milciclib and gemcitabine in NSCLC subjects with an associated pan KRAS-positive mutations.


1. Miller KD, Nogueira L, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69(5):363-385.

2. Walters S, Maringe C, Coleman MP, et al. Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007. Thorax. 2013;68(6):551-564.

3. Howlader N, Forjaz G, Mooradian MJ, et al. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. The New England journal of medicine. 2020;383(7):640-649.