Onconova Therapeutics, Inc. (NASDAQ:ONTX) a biopharmaceutical company focused on discovering and developing novel products to treat cancer, today announced that INSPIRE, the company's pivotal Phase 3 study assessing the efficacy and safety of IV rigosertib in higher-risk MDS (HR-MDS) patients, did not meet its primary endpoint of improved survival.
"Onconova would like to thank the MDS community for its participation in the INSPIRE trial. We report these results with great disappointment, and we remain deeply indebted to every patient, physician, and family member involved in the study," said Steven M. Fruchtman, M.D., President and Chief Executive Officer. "Onconova is fortunate to have built a product pipeline that includes multiple promising agents, including oral rigosertib and ON 123300. Both compounds target meaningful cancer pathways, and we look forward to further efforts with these programs. The Company will review pipeline and in-licensing opportunities both internally and with external advisors."
The primary endpoint of the trial was overall survival, comparing IV rigosertib plus best supportive care to physician's choice (PC) plus best supportive care in patients who had progressed on, failed to respond to, or relapsed after previous treatment with a hypomethylating agent (HMA) within nine cycles over the course of one year after initiation of HMA treatment. A pre-specified analysis in the very high risk (VHR-MDS) patient subgroup was also conducted.
Results of INSPIRE demonstrated that in the intent-to-treat analysis patients randomized to IV rigosertib achieved overall survival of 6.4 months, versus 6.3 months for PC (p=0.33) in the overall HR-MDS population. Overall survival in the pre-specified VHR-MDS subgroup of patients was also not significantly different between the two study arms. There was an increase in overall survival in the PC arm post-interim analysis that was unexpected. The Company is conducting additional analyses.
Safety analysis indicates that IV rigosertib was generally well tolerated, with reported adverse events similar to those observed in previous clinical studies with IV rigosertib in MDS. Serious adverse events (SAEs) were uncommon, with a similar profile of SAEs in both study arms.
"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, M.D., Chief Medical Officer of Onconova. "We plan to take learnings from genomic analyses of the INSPIRE trial to inform the future development of rigosertib. We also look forward to the continued expansion of the investigator-initiated study program with oral rigosertib beyond the ongoing Phase 1/2a study in KRAS+ lung adenocarcinoma into additional solid tumors. Our novel CDK4/6 + ARK5 inhibitor, ON 123300, could also represent a meaningful advance over existing products."
The Company will host a conference call today, August 24, 2020, at 8:30 a.m. Eastern Time. Interested parties who wish to participate in the conference call may do so by dialing (855) 428-5741 for domestic callers and (210) 229-8823 for international callers, and using conference ID 8087044.