On December 14, 2022 EpicentRx Inc. ("EpicentRx"), a leading-edge, clinical stage biopharmaceutical company that uses groundbreaking science to treat cancer and inflammatory-driven diseases, reported the publication of a randomized, Phase 2 trial which demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) benefit for the small molecule NLRP3 inhibitor, RRx-001, plus irinotecan versus standard of care regorafenib in patients with advanced colorectal cancer (Press release, EpicentRx, DEC 14, 2022, View Source [SID1234625255]). The trial, ROCKET, included patients with third- or fourth-line colorectal cancer that previously received the irinotecan-containing chemotherapy regimen, FOLFIRI.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The ROCKET data was published in the December 2022 issue of the journal Clinical Colorectal Cancer.
Regorafenib, a poorly tolerated multi-kinase inhibitor, was FDA-approved in third- or fourth-line colorectal cancer based on a Phase 3 study, which demonstrated a 6.4-month overall survival and a 1.9-month progression free survival.[1]
In the ROCKET trial, 34 patients were randomized 2:1 to receive a priming dose of RRx-001 4 mg IV weekly for two months followed by irinotecan, a chemotherapy agent, associated with a 40% rate of severe diarrhea, which they had previously received and failed, at a dose of 180 mg per meter squared given every two weeks until progression versus regorafenib 160 mg given by mouth, three weeks on/one week off until progression.
The median overall survival was 8.6 months for RRx-001 plus irinotecan and 4.7 months for regorafenib. Median progression free survival was 6.1 months for RRx-001 plus irinotecan vs. 1.7 months for regorafenib, a statistically significant result (two-sided log-rank test, p = 0.0030). Overall response rate was 20.8% for RRx-001 plus irinotecan vs. no response for regorafenib. Moreover, the toxicity profile of RRx-001 plus irinotecan was substantially improved compared with regorafenib. Also, there were no observed cases of severe diarrhea with irinotecan, likely due to protection of the gastrointestinal (GI) tract from RRx-001. Reduction or prevention of side effects from chemotherapy, like severe diarrhea, leads to less dose delays or dose reductions and consequently improves antitumor outcomes.
The prognosis for patients with CRC has historically been poor in later lines of therapy with response rates of approximately 1-2% and median PFS of approximately two months. [2]
According to EpicentRx CEO and practicing gastrointestinal oncologist, Dr. Tony Reid MD, PhD, "Granted, ROCKET was a small trial; however, as a GI oncologist, treatment with regorafenib is commonly associated with significant skin irritation and fatigue, among other symptoms. I think oncologists would welcome a better-tolerated, more active alternative for colorectal cancer patients that have progressed on front-line therapy. Hence, these results from ROCKET, if confirmed in a Phase 3 trial, would likely lead to additional options for third line colorectal cancer and beyond treatment."
About RRx-001
RRx-001 is a highly selective NLRP3 inhibitor with vascular normalization and tumor associated macrophage polarization properties that resensitizes tumors to previously administered therapies. RRx-001 is under investigation in a Phase 3 trial for the treatment of small cell lung cancer (SCLC), and in a Phase 2 trial for protection against oral mucositis in first line head and neck cancer. It is also under development as a medical countermeasure for nuclear and radiological emergencies and as a treatment for neurodegenerative diseases like Parkinson’s and ALS/MND. For more information visit www.epicentrx.com.