Maximum Tolerated Dose Identified for Once-Every-Three-Weeks Regimen
WALTHAM, MA, USA I March 21, 2016 I Cerulean Pharma Inc. (NASDAQ:CERU), a clinical-stage company developing nanoparticle-drug conjugates (NDCs), today announced the presentation of data from the Company’s ongoing Phase 1/2a study of CRLX301 in patients with refractory solid tumors. CRLX301 is an NDC designed to concentrate in tumors and slowly release its payload, docetaxel, inside the cancer cells while sparing healthy tissue. The abstract, entitled “A phase 1 study of CRLX301, a novel Nanoparticle-Drug Conjugate (NDC) containing docetaxel, in patients with refractory solid tumors,” will be presented during a poster session at the 14th International Congress on Targeted Anticancer Therapies being held March 21-23, 2016, in Washington, DC.
“There were several important outcomes from the dose-escalation portion of this study, including the determination of the maximum tolerated dose (MTD) on a once-every-three-weeks (Q3W) dosing schedule. CRLX301 was generally well tolerated, showed hints of antitumor activity, and exhibited a differentiated pharmacokinetic (PK) profile compared to docetaxel,” said Adrian Senderowicz, M.D., Senior Vice President & Chief Medical Officer of Cerulean. “These early data suggest that CRLX301 has the potential to be a better-tolerated taxane that could be combined with other cancer treatments to provide better outcomes for patients. As a result of what we learned in Phase 1, we are moving into a Phase 2a, where we will look for further signals of activity.”
Dr. Senderowicz added: “Taxanes sometimes are more active when administered on a weekly basis, so we are exploring the safety of weekly administration (QW) of CRLX301. Once we have a recommended Phase 2 dose (RP2D) for QW dosing, we will advance that regimen into Phase 2a as well. Upon completion of this trial, we will have thoroughly explored both dosing schedules in order to choose the optimal regimen for future pivotal studies with CRLX301.”
Highlights from the data include:
- Twenty patients were treated across six dosing cohorts.
- Two of the six patients treated at the highest dose level, 90 mg/m2, experienced dose limiting toxicities (DLTs). The DLTs were reversible grade 3 transaminases with grade 2 bilirubin, which completely resolved without medical intervention and uncomplicated grade 4 febrile neutropenia.
- None of the six patients treated at the second highest dose level, 75 mg/m2, experienced DLTs, and the MTD of CRLX301 using the Q3W dosing schedule is 75 mg/m2.
- CRLX301 is generally well tolerated. Across all cohorts, reported drug-related adverse events (AEs) were toxicities associated with docetaxel, with no unexpected toxicities. The majority of the AEs were mild to moderate and transient. The most common drug-related AEs of grade ≥3 were neutropenia and hypersensitivity/infusion reaction.
- Hints of clinical activity include (a) a patient with B-RAF mutant adenocarcinoma of unknown primary, previously refractory to vemurafenib that demonstrated clear evidence of tumor shrinkage as evidenced by CT and PET scans and (b) two patients with prolonged stable disease (7 and 16 cycles).
- PK analysis suggests that CRLX301 stays intact in circulation for an extended period of time, resulting in ~100 times greater plasma exposure of the intact NDC relative to published data for docetaxel. Importantly, there was a 20-fold reduction of the maximal concentration (Cmax) of released docetaxel when compared to published data of docetaxel.
- Expansion cohorts are being launched to further explore the tolerability and efficacy of the Q3W MTD.
- Evaluation of the QW dosing schedule of CRLX301 has commenced.
Information presented in this poster is through February 24, 2016. Information in the abstract was as of January 5, 2016.
Electronic copies of the poster are available upon request by emailing ir@ceruleanrx.com.
About CRLX301
CRLX301 is a dynamically tumor-targeted NDC designed to concentrate in tumors and slowly release its anti-cancer payload, docetaxel, inside tumor cells. In preclinical studies, CRLX301 delivers up to 10 times more docetaxel into tumors, compared to an equivalent milligram dose of commercially available docetaxel and was similar to or better than docetaxel in seven of seven animal models, with a statistically significant survival benefit seen in five of those seven models. In addition, preclinical data show that CRLX301 had lower toxicity than has been reported with docetaxel in similar preclinical studies. CRLX301 is in Phase 1/2a clinical development.
About Cerulean Pharma
The Cerulean team is committed to improving treatment for people living with cancer. We apply our Dynamic Tumor Targeting™ Platform to create a portfolio of NDCs designed to selectively attack tumor cells, reduce toxicity by sparing the body’s normal cells, and enable therapeutic combinations. Our first platform-generated NDC clinical candidate, CRLX101, is in multiple clinical trials in combination with other cancer treatments, all of which aim to unlock the power of combination therapy. Our second platform-generated NDC clinical candidate, CRLX301, is in a Phase 1/2a clinical trial. For more information, please visit www.ceruleanrx.com.
About Cerulean’s Dynamic Tumor Targeting™ Platform
Cerulean’s Dynamic Tumor Targeting Platform creates NDCs that are designed to provide safer and more effective cancer treatments. We believe our NDCs concentrate their anti-cancer payloads inside tumors while sparing normal tissue because they are small enough to pass through the “leaky” vasculature present in tumors but are too large to pass through the wall of healthy blood vessels. Once inside tumors, our NDCs enter tumor cells where they slowly release anti-cancer payloads from within the tumor cells.
SOURCE: Cerulean Pharma
Post Views: 99
Maximum Tolerated Dose Identified for Once-Every-Three-Weeks Regimen
WALTHAM, MA, USA I March 21, 2016 I Cerulean Pharma Inc. (NASDAQ:CERU), a clinical-stage company developing nanoparticle-drug conjugates (NDCs), today announced the presentation of data from the Company’s ongoing Phase 1/2a study of CRLX301 in patients with refractory solid tumors. CRLX301 is an NDC designed to concentrate in tumors and slowly release its payload, docetaxel, inside the cancer cells while sparing healthy tissue. The abstract, entitled “A phase 1 study of CRLX301, a novel Nanoparticle-Drug Conjugate (NDC) containing docetaxel, in patients with refractory solid tumors,” will be presented during a poster session at the 14th International Congress on Targeted Anticancer Therapies being held March 21-23, 2016, in Washington, DC.
“There were several important outcomes from the dose-escalation portion of this study, including the determination of the maximum tolerated dose (MTD) on a once-every-three-weeks (Q3W) dosing schedule. CRLX301 was generally well tolerated, showed hints of antitumor activity, and exhibited a differentiated pharmacokinetic (PK) profile compared to docetaxel,” said Adrian Senderowicz, M.D., Senior Vice President & Chief Medical Officer of Cerulean. “These early data suggest that CRLX301 has the potential to be a better-tolerated taxane that could be combined with other cancer treatments to provide better outcomes for patients. As a result of what we learned in Phase 1, we are moving into a Phase 2a, where we will look for further signals of activity.”
Dr. Senderowicz added: “Taxanes sometimes are more active when administered on a weekly basis, so we are exploring the safety of weekly administration (QW) of CRLX301. Once we have a recommended Phase 2 dose (RP2D) for QW dosing, we will advance that regimen into Phase 2a as well. Upon completion of this trial, we will have thoroughly explored both dosing schedules in order to choose the optimal regimen for future pivotal studies with CRLX301.”
Highlights from the data include:
- Twenty patients were treated across six dosing cohorts.
- Two of the six patients treated at the highest dose level, 90 mg/m2, experienced dose limiting toxicities (DLTs). The DLTs were reversible grade 3 transaminases with grade 2 bilirubin, which completely resolved without medical intervention and uncomplicated grade 4 febrile neutropenia.
- None of the six patients treated at the second highest dose level, 75 mg/m2, experienced DLTs, and the MTD of CRLX301 using the Q3W dosing schedule is 75 mg/m2.
- CRLX301 is generally well tolerated. Across all cohorts, reported drug-related adverse events (AEs) were toxicities associated with docetaxel, with no unexpected toxicities. The majority of the AEs were mild to moderate and transient. The most common drug-related AEs of grade ≥3 were neutropenia and hypersensitivity/infusion reaction.
- Hints of clinical activity include (a) a patient with B-RAF mutant adenocarcinoma of unknown primary, previously refractory to vemurafenib that demonstrated clear evidence of tumor shrinkage as evidenced by CT and PET scans and (b) two patients with prolonged stable disease (7 and 16 cycles).
- PK analysis suggests that CRLX301 stays intact in circulation for an extended period of time, resulting in ~100 times greater plasma exposure of the intact NDC relative to published data for docetaxel. Importantly, there was a 20-fold reduction of the maximal concentration (Cmax) of released docetaxel when compared to published data of docetaxel.
- Expansion cohorts are being launched to further explore the tolerability and efficacy of the Q3W MTD.
- Evaluation of the QW dosing schedule of CRLX301 has commenced.
Information presented in this poster is through February 24, 2016. Information in the abstract was as of January 5, 2016.
Electronic copies of the poster are available upon request by emailing ir@ceruleanrx.com.
About CRLX301
CRLX301 is a dynamically tumor-targeted NDC designed to concentrate in tumors and slowly release its anti-cancer payload, docetaxel, inside tumor cells. In preclinical studies, CRLX301 delivers up to 10 times more docetaxel into tumors, compared to an equivalent milligram dose of commercially available docetaxel and was similar to or better than docetaxel in seven of seven animal models, with a statistically significant survival benefit seen in five of those seven models. In addition, preclinical data show that CRLX301 had lower toxicity than has been reported with docetaxel in similar preclinical studies. CRLX301 is in Phase 1/2a clinical development.
About Cerulean Pharma
The Cerulean team is committed to improving treatment for people living with cancer. We apply our Dynamic Tumor Targeting™ Platform to create a portfolio of NDCs designed to selectively attack tumor cells, reduce toxicity by sparing the body’s normal cells, and enable therapeutic combinations. Our first platform-generated NDC clinical candidate, CRLX101, is in multiple clinical trials in combination with other cancer treatments, all of which aim to unlock the power of combination therapy. Our second platform-generated NDC clinical candidate, CRLX301, is in a Phase 1/2a clinical trial. For more information, please visit www.ceruleanrx.com.
About Cerulean’s Dynamic Tumor Targeting™ Platform
Cerulean’s Dynamic Tumor Targeting Platform creates NDCs that are designed to provide safer and more effective cancer treatments. We believe our NDCs concentrate their anti-cancer payloads inside tumors while sparing normal tissue because they are small enough to pass through the “leaky” vasculature present in tumors but are too large to pass through the wall of healthy blood vessels. Once inside tumors, our NDCs enter tumor cells where they slowly release anti-cancer payloads from within the tumor cells.
SOURCE: Cerulean Pharma
Post Views: 99
