Onconova Therapeutics Inc. (NASDAQ:ONTX) Commence Enrolment in Phase 1/2a Rigosertib Plus Nivolumab Study in KRAS+ lung adenocarcinoma

Onconova Therapeutics Inc. (NASDAQ:ONTX) has enrolled in Phase 1/2a oral rigosertib, and nivolumab study in advanced metastatic KRAS mutated lung adenocarcinoma.

KRAS mutation main genetic driver of NSCLC

Onconova Steven Fruchtman stated that although KRAS mutation was discovered almost 30 years ago, there has been little progress in terms of KRAS+ focused treatments. The CEO said more than 50% of non-small cell lung cancers (NSCLC) are categorized as lung adenocarcinomas, with most having KRAS mutation as the main genetic driver. Fruchtman stated that the work under the leadership of Dr. Rajwanth Veluswamy at the Icahn School of medicine is a significant milestone towards establishing if rigosertib used as a RAS mimetic can be a treatment to this patient population.

The trial, which is an investigator-instigated study, is a dose-escalating, open-label first phase study. It will be followed by a dose-expansion phase 2a study combining oral rigosertib with nivolumab in treating patients with metastatic KRAS+ lung adenocarcinoma that have progressed on standard care treatment. The study will also evaluate the efficacy and safety of rigosertib.

Study to assess the safety and tolerability of rigosertib and nivolumab combination

Dr. Rajwanth stated that the rigosertib combination with nivolumab targets two vital oncogenic pathways in cancer biology. Rajwanth stated that the study will assess the tolerability and safety of the combination in KRAS mutated non-small cell lung cancer where patients have become nonresponsive to frontline immunotherapy. Equally, the study will evaluate the efficacy of these combinations in the NSCLC subset as well as determine if rigosertib can restore sensitivity to PD-1 blockade.

Rigosertib is a novel third small molecule, which is Onconova’s lead candidate. A preclinical model study indicated that rigosertib has the ability to block cellular indication by targeting the RAS effector pathways. Currently, the company is in conducting clinical studies evaluating single-agent IV rigosertib in high-risk second-line MDS patients. Equally the company is studying a combination of oral rigosertib and azacitidine in refractory high-risk MDS and HMA naïve patients.