Updated RRx-001 Preliminary Phase 2 Trial Data
Posted: Tue Mar 24, 2015 12:00 am
I posted about this new drug currently in Phase 2 last week, I wanted to post some updated information that hit the web this week.
Trial: https://clinicaltrials.gov/ct2/show/NCT ... 001&rank=2 In addition to the west coast trial sites shown, Walter Reed military hospital in DC is a trial site for patients eligible for care at a military hospital. I heard that they may open up that trial site to civilians in the future.
Updated info: http://www.ncbi.nlm.nih.gov/m/pubmed/25 ... arker%5bau (and pasted in full below, I bolded what I thought were some key points). It is early in the Phase 2, so patient numbers are small so far but it is a randomized trial against standard of care and so far the results have been very consistent with the efficacy they observed in the Phase 1 trial. Note that the PFS number is listed as "ongoing" - that is the calculated number as of a February data cutoff point but patients were still stable on trial, so essentially the real median value hasn't been reached yet.
They will also be presenting an update at the big AACR meeting this Spring - it wouldn't surprise me if they also present continued updates at either the ASCO or ESMO meetings.
I find this a fascinating molecule - it has a very unique mechanism of action and clinical profile. Preliminary data seems to indicate efficacy in both KRAS-wt and KRAS-mut.
I'm keeping a very close eye on this one...
-DK
O3.8 Early Results: "ROCKET" a phase II Study of RRx-001, a novel triple epigenetic inhibitor, Resensitization to Irinotecan in Colorectal Cancer.
Authors
Carter C1, Reid T2, Fisher G3, Cho-Phan C4, Kunz P5, Kaiser H6, Oronsky B7, Fanger G7, Caroen S7, Parker C7, Scicinski J7.
Author information
1Walter Reed National Military Medical Center, Bethesda, MD, USA.
2Uc San Diego Moores Cancer Center, La Jolla, CA, USA.
3Stanford Cancer Center, Stanford, CA, USA.
4Stanford School Of Medicine, Stanford, CA, USA.
5Stanford University Medical Center, Stanford, CA, USA.
6Standford University School Of Medicine, Redwood City, CA, USA.
7Epicentrx, Mountain View, CA, USA.
Journal
Ann Oncol. 2015 Mar;26(suppl 2):ii4-ii5.
Affiliation
Abstract
BACKGROUND: RRx-001 is a novel broad-spectrum anticancer agent that triply inhibits DNA methyltransferases (DNA MTases), Histone Deacetylases (HDAC), and Lysine Demethylases. In the first-in-human, Phase I trial, 5/5 patients who progressed on RRx-001 treatment were resensitized to previously refractory irinotecan therapy, hinting at a generalized resensitization effect. A randomized open-label multi-part, multi-center phase II trial of RRx-001 versus regorafenib (ROCKET) is underway to explore the resensitization and/or 'episensitization' potential in irinotecan refractory tumors and its impact on overall survival.
METHODS: 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 16.5 mg/m(2) IV 1x/week or regorafenib 160 mg orally 21 of 28 days until progression or unacceptable toxicity followed by treatment with refractory irinotecan-based therapies.
RESULTS: To date, 23 patients have been randomized with 10 patients evaluable for resensitization. Post RRx-001 patients demonstrated marked decreases in CEA in all 6 patients as compared to 4 patients receiving regorafenib who were too systemically unwell to proceed to subsequent treatment. Progression free survival (ongoing) for RRx-001 + irinotecan is 5.9 months compared 0.92 months on Regorafenib + irinotecan. Combined Disease Control Rate (SD + PR) for the combination of RRx-001 and reintroduction of Irinotecan based therapy is currently 100%, whereas no patients to date randomized to the regorafenib arm have been able to start irinotecan based therapy secondary to decreasing performance status.
CONCLUSIONS: 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 and may be a major advancement in epigenetic therapy. RRx-001 is a novel pan-epigenetic inhibitor that may potentially offer improved QOL and overall survival over currently approved therapy in the chemotherapy refractory colorectal cancer.
Trial: https://clinicaltrials.gov/ct2/show/NCT ... 001&rank=2 In addition to the west coast trial sites shown, Walter Reed military hospital in DC is a trial site for patients eligible for care at a military hospital. I heard that they may open up that trial site to civilians in the future.
Updated info: http://www.ncbi.nlm.nih.gov/m/pubmed/25 ... arker%5bau (and pasted in full below, I bolded what I thought were some key points). It is early in the Phase 2, so patient numbers are small so far but it is a randomized trial against standard of care and so far the results have been very consistent with the efficacy they observed in the Phase 1 trial. Note that the PFS number is listed as "ongoing" - that is the calculated number as of a February data cutoff point but patients were still stable on trial, so essentially the real median value hasn't been reached yet.
They will also be presenting an update at the big AACR meeting this Spring - it wouldn't surprise me if they also present continued updates at either the ASCO or ESMO meetings.
I find this a fascinating molecule - it has a very unique mechanism of action and clinical profile. Preliminary data seems to indicate efficacy in both KRAS-wt and KRAS-mut.
I'm keeping a very close eye on this one...
-DK
O3.8 Early Results: "ROCKET" a phase II Study of RRx-001, a novel triple epigenetic inhibitor, Resensitization to Irinotecan in Colorectal Cancer.
Authors
Carter C1, Reid T2, Fisher G3, Cho-Phan C4, Kunz P5, Kaiser H6, Oronsky B7, Fanger G7, Caroen S7, Parker C7, Scicinski J7.
Author information
1Walter Reed National Military Medical Center, Bethesda, MD, USA.
2Uc San Diego Moores Cancer Center, La Jolla, CA, USA.
3Stanford Cancer Center, Stanford, CA, USA.
4Stanford School Of Medicine, Stanford, CA, USA.
5Stanford University Medical Center, Stanford, CA, USA.
6Standford University School Of Medicine, Redwood City, CA, USA.
7Epicentrx, Mountain View, CA, USA.
Journal
Ann Oncol. 2015 Mar;26(suppl 2):ii4-ii5.
Affiliation
Abstract
BACKGROUND: RRx-001 is a novel broad-spectrum anticancer agent that triply inhibits DNA methyltransferases (DNA MTases), Histone Deacetylases (HDAC), and Lysine Demethylases. In the first-in-human, Phase I trial, 5/5 patients who progressed on RRx-001 treatment were resensitized to previously refractory irinotecan therapy, hinting at a generalized resensitization effect. A randomized open-label multi-part, multi-center phase II trial of RRx-001 versus regorafenib (ROCKET) is underway to explore the resensitization and/or 'episensitization' potential in irinotecan refractory tumors and its impact on overall survival.
METHODS: 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 16.5 mg/m(2) IV 1x/week or regorafenib 160 mg orally 21 of 28 days until progression or unacceptable toxicity followed by treatment with refractory irinotecan-based therapies.
RESULTS: To date, 23 patients have been randomized with 10 patients evaluable for resensitization. Post RRx-001 patients demonstrated marked decreases in CEA in all 6 patients as compared to 4 patients receiving regorafenib who were too systemically unwell to proceed to subsequent treatment. Progression free survival (ongoing) for RRx-001 + irinotecan is 5.9 months compared 0.92 months on Regorafenib + irinotecan. Combined Disease Control Rate (SD + PR) for the combination of RRx-001 and reintroduction of Irinotecan based therapy is currently 100%, whereas no patients to date randomized to the regorafenib arm have been able to start irinotecan based therapy secondary to decreasing performance status.
CONCLUSIONS: 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 and may be a major advancement in epigenetic therapy. RRx-001 is a novel pan-epigenetic inhibitor that may potentially offer improved QOL and overall survival over currently approved therapy in the chemotherapy refractory colorectal cancer.