Phase 3 INSPIRE Study Fails to Meet Primary End Point of Improved Survival

August 24, 2020

The study evaluated the efficacy and safety of IV rigosertib in patients with high-risk MDS who had progressed on, failed to respond to, or relapsed after previous treatment with an HMA within 9 cycles over the course of 1 year after initiation of HMA treatment.

The pivotal phase 3 INSPIRE study, assessing the efficacy and safety of intravenous (IV) rigosertib in patients with higher-risk myelodysplastic syndrome (HR-MDS), did not meet its primary end point of improved survival, according to Onconova Therapeutics, the developer of the agent.

“Onconova would like to thank the MDS community for its participation in the INSPIRE trial,” Steven M. Fruchtman, MD, president and chief executive officer at Onconova, said in a press release. “We report these results with great disappointment, and we remain deeply indebted to every patient, physician, and family member involved in the study.”

The global, multicenter, randomized, controlled, phase 3 INSPIRE study evaluated the efficacy and safety of IV rigosertib in patients with HR-MDS who had progressed on, failed to respond to, or relapsed after previous treatment with a hypomethylating agent (HMA) within 9 cycles over the course of 1 year after initiation of HMA treatment. Notably, this time frame was based on National Comprehensive Cancer Network (NCCN) guidelines. A pre-specified analysis in a very high-risk (VHR-MDS) patient subgroup was also conducted.

Patients were randomized 2:1 to receive either IV rigosertib plus best supportive care or physician's choice plus best supportive care. Overall, results from the study demonstrated that in the intent-to-treat analysis, patients randomized to IV rigosertib achieved an overall survival (OS) of 6.4 months versus 6.3 months for physician’s choice (P = .33) in the total HR-MDS population.

Moreover, OS in the pre-specified VHR-MDS subgroup of patients was also not significantly different between the 2 study arms. However, there was an increase in OS in the physician’s choice arm post-interim analysis that was unexpected. Moving forward, Onconova Therapeutics intends to conduct additional analyses to further validate these study findings.

Safety analyses indicated that IV rigosertib was generally well tolerated and reported adverse events (AEs) were found to be similar to those observed in previous clinical studies of the agent in MDS. Serious AEs were uncommon, with a similar profile of serious AEs observed 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,” Richard C. Woodman, MD, chief medical officer of Onconova, said in the release. “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 [positive] lung adenocarcinoma into additional solid tumors,” Woodman continued. “Our novel CDK4/6 [positive] ARK5 inhibitor, ON 123300, could also represent a meaningful advance over existing products.”

Reference:

Onconova Therapeutics Announces Topline Results from the Pivotal Phase 3 INSPIRE Trial [news release]. Newtown, Pennsylvania. Published August 24, 2020. Accessed August 24, 2020. https://www.globenewswire.com/news-release/2020/08/24/2082504/0/en/Onconova-Therapeutics-Announces-Topline-Results-from-the-Pivotal-Phase-3-INSPIRE-Trial.html