Updated Trial Results of Rigosertib, Nivolumab Combination Show Promise in Subset of Patients with Lung Adenocarcinoma


The data show that the maximum tolerated dose of rigosertib in combination with nivolumab was not reached in the 3 cohorts of the trial’s dose-escalation phase in patients with advanced KRAS-positive metastatic lung adenocarcinoma.

The phase 1/2a clinical trial of oral rigosertib plus nivolumab is continuing dose escalation and preliminary data support the observation of how rigosertib augments the body’s response to immune checkpoint inhibition, according to a press release from Onconova Therapeutics.

The trial is evaluating the combination of rigosertib and nivolumab in patients with advanced KRAS-positive metastatic lung adenocarcinoma that has progressed after standard of care treatments with anti-programmed cell death-1 (anti-PD-1) in combination with chemotherapy. Participants have failed multiple lines of prior therapy as well as all immune checkpoint inhibitors in various combinations.

“The preliminary results from this phase 1/2a trial are very encouraging and demonstrate the potential of rigosertib to address a critical unmet medical need by overcoming checkpoint inhibitor resistance in KRAS-mutated lung adenocarcinoma,” said Mark S. Gelder, MD, chief medical officer of Onconova, in the press release. “The observation of preliminary evidence of efficacy in combination with acceptable safety of the doublet in this extremely challenging patient population provides a promising signal.”

The trial includes a dose-escalating phase 1 portion followed by a phase 2a dose expansion portion. According to Onconova, trial participants receive oral rigosertib twice daily on days 1 through 21, in addition to intravenous nivolumab on days 1 and 15 of 28-day cycles. The primary endpoints are safety assessments and overall response rate and secondary endpoints include progression free survival (PFS) and overall survival (OS).

The clinical data to date has provided preliminary evidence of potential anti-cancer activity, according to Onconova. The data show that the maximum tolerated dose of rigosertib in combination with nivolumab was not reached in the 3 cohorts of the trial’s dose-escalation phase.

Investigators are continuing to recruit participants as part of the expansion phase at the highest dose of oral rigosertib. Based on the positive preliminary findings, researchers are preparing a protocol amendment that would allow for the evaluation of increased rigosertib doses in combination with the full dose of nivolumab.

“We are very pleased both with the safety and preliminary efficacy signal we have seen from the KRAS mutated [non-small cell lung cancer] trial to date, considering the multiple lines of therapy many of these patients have previously failed, including checkpoint inhibitors in various combinations,” said Steven M. Fruchtman, MD, president and chief executive officer of Onconova, in the press release. “We are supportive of the plan to expand dose-escalation of rigosertib to determine the optimal recommended phase 2 dose of the combination and are eagerly anticipating results of important correlative science that is part of the trial.”


Onconova Therapeutics Provides an Update on the Phase 1/2a Trial of Rigosertib-Nivolumab Combination in KRAS+ Non-Small Cell Lung Cancer. News release. June 28, 2021. Accessed July 7, 2021. https://www.globenewswire.com/en/news-release/2021/06/28/2253816/0/en/Onconova-Therapeutics-Provides-an-Update-on-the-Phase-1-2a-Trial-of-Rigosertib-Nivolumab-Combination-in-KRAS-Non-Small-Cell-Lung-Cancer.html

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