When given alongside best supportive care, rigosertib failed to prolong the survival of patients with higher-risk myelodysplastic syndromes (HR-MDS), a group of blood cancers that often progress to acute myeloid leukemia (AML), a Phase 3 trial has found.
The main goal of the INSPIRE study (NCT02562443) was to assess if the combination of intravenous (into-the-vein) rigosertib, Onconova Therapeutics’ lead anti-cancer candidate, and best supportive care would be superior to standard treatment with an approved medication of choice plus supportive care at prolonging the life of patients with HR-MDS.
This endpoint was assessed in the overall population of HR-MDS patients enrolled in the study, as well as in the subset of those with very high risk MDS (VHR-MDS). All patients enrolled in the trial had failed to respond, relapsed, or had their disease worsen after receiving treatment with a hypomethylating agent, either azacitidine or decitabine.
Study findings now announced by the company showed the trial failed to meet its primary goal of superiority, with patients given the rigosertib combo therapy living approximately 6.4 months, while those receiving standard treatment had an overall survival of 6.3 months.
As was the case in the overall population of participants in the study, no significant differences in overall survival were seen between the two treatment groups in the subset of those with VHR-MDS.
However, a post-interim analysis revealed there was an unexpected increase in the overall survival of those receiving standard treatment. Onconova is currently conducting additional analyses to clarify those findings.
Analyses showed that intravenous rigosertib was generally safe and well-tolerated, with side effects similar to those reported in previous studies of MDS. Serious adverse events were scarce and similar in both treatment groups.
“We report these results with great disappointment, and we remain deeply indebted to every patient, physician, and family member involved in the study,” Steven M. Fruchtman, MD, president and CEO of Onconova, said in a press release.
“Onconova is fortunate to have built a product pipeline that includes multiple promising agents, including oral rigosertib and ON 123300,” he added. “Both compounds target meaningful cancer pathways, and we look forward to further efforts with these programs.”
Rigosertib is a small molecule that resembles Ras, a signaling protein that is able to interact with many other proteins and activate signaling pathways used by cancer cells to grow and live longer. By binding to proteins that Ras would normally interact with and interrupting the activation of these signaling cascades, rigosertib is expected to slow cancer progression.
“While the INSPIRE data readout in HR-MDS is a disappointment, as a RAS pathway inhibitor, oral rigosertib could address a number of oncology settings outside of hematology,” said Richard C. Woodman, MD, chief medical officer of Onconova.
The company is now planning to use data from the trial to inform the future development of oral rigosertib, and expand its clinical trial program to include solid cancers other than lung adenocarcinoma, where the medication is already being tested in a Phase 1/2a trial (NCT04263090).
In addition to rigosertib, the company is also planning to explore the therapeutic potential of its novel anti-cancer therapy ON 123300 for the treatment of different types of solid tumors.