Onconova Therapeutics, Inc. announced preliminary safety and efficacy data from an investigator-initiated Phase 1/2a trial of oral rigosertib plus the immune checkpoint inhibitor nivolumab in advanced KRAS mutated (KRAS+) non-small cell lung cancer (NSCLC). The data, which are being featured in a presentation at the 3rd Annual RAS Targeted Drug Development Summit, support the potential anti-cancer activity of rigosertib-nivolumab combination therapy in this indication and show that the doublet has been well tolerated to-date. Three quarters of patients enrolled in the trial have failed two or more lines of prior therapy and all have failed immune checkpoint inhibitors in various combinations. Demographics: All enrolled patients (12/12) failed at least one line of prior therapy with a PD-1 checkpoint inhibitor (includes evaluable and non-evaluable patients). 9 of 12 (75%) enrolled patients failed at least two prior lines of therapy. Response Results: 2 of 7 (29%) evaluable patients achieved a partial response (PR). PRs were observed in patients with two distinct KRAS mutations (G12C, G12V). 3 of 7 (43%) evaluable patients achieved disease control (PR or stable disease). 4 of 7 (57%) evaluable patients experienced progressive disease. Adverse Event Results: The combination of rigosertib and nivolumab has been well tolerated and the maximum tolerated dose has not been reached to-date. Treatment related adverse events were mostly mild with two grade 3 adverse events. 3 patients discontinued study drug (2 grade 2 genitourinary toxicities, 1 dose limiting grade 3 hyponatremia). No unexpected safety events or synergistic toxicities have been observed. This Phase 1/2a trial is designed to evaluate the combination of rigosertib and nivolumab in advanced KRAS+ metastatic NSCLC patients who have progressed on standard of care with anti-PD-1 monotherapy or anti-PD-1 in combination with chemotherapy. It includes a dose-escalating Phase 1 portion followed by a Phase 2a dose-expansion portion. Patients in the trial receive oral rigosertib twice daily on days 1-21, and intravenous nivolumab on days 1 and 15 of 28-day cycles. The primary endpoints of the trial are safety assessments to determine maximum tolerated dose and overall response rate. Secondary endpoints include progression free survival and overall survival.