Interim Analysis for Phase Ib Study of Resiniferatoxin Generates Positive Data

An interim analysis of the ongoing phase Ib study of resiniferatoxin (RTX), administered via epidural route in patients with intractable cancer pain, has produced positive data, according to Sorrento Therapeutics, the agent’s developer.

The study is currently completing enrollment of an additional 25 ug expansion dose cohort. Based on the full study results, a dose will be selected for the drug to proceed to phase III pivotal trials in patients with advanced cancer pain.

“We are encouraged by the benefits of using RTX to treat intractable pain in patients with metastatic cancer,” Srdjan S. Nedeljkovic, MD, associate professor of anesthesia at the Brigham and Women’s Hospital at Harvard Medical School, said in a press release. “Even in patients with high levels of pain, RTX given via an epidural injection has been found to reduce pain sensitivity without having any long-term adverse safety consequences. The addition of RTX to existing cancer pain therapies represents a positive step forward in improving the care of patients with intractable cancer pain and offers the hope of enhancing the overall quality of life experienced by this population.” 

The phase Ib open-label study is being used for dose escalation to evaluate the safety and preliminary efficacy of a single epidural administration of resiniferatoxin for the treatment of intractable pain caused by cancer. The initial expectations for safety and efficacy have been met for the study, however optimal dose selection will follow the assessment of the additional dose group in which 25 ug is also being assessed. Currently, after Institutional Review Board approval was obtained, and with oversight by an independent data monitoring committee, data is available from 14 participants with intractable cancer-related pain who were given a single epidural injection of RTX from 0.4 to 15 ug.

The ongoing trial will follow patients for at least 84 days. Thus far, the lower doses of 0.4, 1.0, 2.0, and 4.0 ug did not demonstrate notable pain relief, though they did permit dose escalation to the next designated dose level based on how well the drug was tolerated. 

Three patients had marked pain relief shortly after their initial administration that was still observed weeks after treatment, including 1 of 3 subjects who received 8 ug (a 58-year-old woman with gastrointestinal stromal cancer with severe lower back pain reported a decrease in numerical pain rating scale [NPRS] scores from >6/10 to 2/10, and 2 of 3 who received 15 ug (a 62-year-old man with rectal cancer noted significant improvement in pain, physical strength, mood, and appetite with NPRS scores reduced from 7-8/10 to 3/10, and a 57-year-old man with multiple myeloma and severe pain in his back, hips, and lower extremities subsequently reported mild pain in the target areas after RTX injection). Improvements reported in pain and mobility within 24 hours of dosing in the 3 responders at the higher dose levels of the injection suggests the clinical potential of the drug for intractable cancer pain. 

No dose limiting toxicities or notable adverse events unrelated to progression of underlying disease have been encountered for any of the participants. The most common treatment-related adverse event was transient post-procedural pain, with 7 of 14 subjects reporting moderate severity. Two other treatment-related adverse events of moderate severity observed were back pain and increase in blood pressure in a patient. However, all events resolved in less than 2 days following drug administration.

Safety in the higher dose cohort is anticipated to be supportive for testing resiniferatoxin epidural administration in other advanced non-cancer disease related unmet clinical needs, with a starting dose at 15 or 25 ug depending on the indication considered. 

The developer intends to present detailed results from the completed study upon completion of the additional expansion cohort later this year. Additionally, a pivotal phase III trial is being planned using epidural resiniferatoxin for severe pain states correlated with advanced disease. 

Reference:

Sorrento Therapeutics Presents Interim Positive Results of Phase 1b Resiniferatoxin (RTX) in Cancer Pain Trial [news release]. San Diego, California. Published February 27, 2020. investors.sorrentotherapeutics.com/news-releases/news-release-details/sorrento-therapeutics-presents-interim-positive-results-phase-1b. Accessed March 2, 2020.