The Development Of RRx-001, A Novel Nitric-Oxide-Mediated Epigenetically Active Anticancer Agent.
RRx-001 is a novel NO and hypoxia mediated anticancer agent with epigenetic activity. In the first-in-human, Phase I trial, 5/5 patients who progressed on RRx-001 treatment were resensitized to previously refractory therapy, hinting at a generalized resensitization effect.



A randomized open-label multi-part, multi-center phase II trial of RRx-001 versus regorafenib (ROCKET) has commenced to explore the resensitization and/or 'episensitization' potential in irinotecan refractory tumors and its impact on overall survival.



Patients with irinotecan-refractory metastatic colorectal cancer with an ECOG PS 0-1 who progressed on oxaliplatin-, and irinotecan-based regimens with or without bevacizumab, cetuximab or panitumumab are randomized 2:1 to receive RRx-001 16.5mg/m2IV 1x/week or regorafenib 160mg orally 21 of 28 days until progression or unacceptable toxicity followed by treatment with refractory irinotecan-based therapies.



To date, 26 patients have been randomized with 18 patients evaluable for resensitization. Post RRx-001 patients demonstrated marked decreases in CEA in 12/13 patients as compared to 5 patients receiving regorafenib who were too systemically unwell to proceed to subsequent treatment. Progression free survival (ongoing) for RRx-001+irinotecan is 4.9 months compared 1.8 months on Regorafenib+irinotecan.



Early results in the ROCKET study suggest that RRx-001-mediated resensitization to previously refractory therapies may have a generalized effect, independent of KRAS or p53 status. These early results are intriguing, suggesting improved QOL and overall survival over currently approved therapy in the chemotherapy refractory colorectal cancer.
EpicentRx, Inc, Mountain View, CA, USA.
Jan
J
Scicinski
Stanford Comprehensive Cancer Center, Stanford, CA, USA.
George
G
Fisher
Walter Reed National Military Medical Center, Bethesda, MD, USA.
Corey
C
Carter
Stanford Comprehensive Cancer Center, Stanford, CA, USA.
Cheryl
C
Cho-Phan
Stanford Comprehensive Cancer Center, Stanford, CA, USA.
Pamela
P
Kunz
Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA.
Shoucheng
S
Ning
Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA.
Susan
S
Knox
UCSD Moores Cancer Center, La Jolla, CA, USA.
Bryan
B
Oronsky
UCSD Moores Cancer Center, La Jolla, CA, USA.
Scott
S
Caroen
UCSD Moores Cancer Center, La Jolla, CA, USA.
Christopher
C
Parker
UCSD Moores Cancer Center, La Jolla, CA, USA.
Gary
G
Fanger
EpicentRx, Inc, Mountain View, CA, USA.
Tony
T
Reid
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D000911:Antibodies, Monoclonal; D001384:Azetidines; D009574:Nitro Compounds; D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D011725:Pyridines; C577469:RRx-001; D000077150:Oxaliplatin; C559147:regorafenib; D000068258:Bevacizumab; D000077544:Panitumumab; D000077146:Irinotecan; D000068818:Cetuximab; D002166:Camptothecin