Release Details
Cerulean Announces Data Presentations at the 2016 American Association for Cancer Research Annual Meeting
One Late-Breaking Poster Reporting Interim Phase 2 CRLX101 Data in Ovarian Cancer
Four Poster Presentations Featuring Preclinical and Clinical Data for CRLX101 and CRLX301
"The scientific research presented by Cerulean this year at AACR
continues to highlight the progress of our Dynamic Tumor Targeting™
Platform in the development of cutting-edge cancer therapies that have
the potential to be more tolerable and effective," said Christopher D.
Details of the AACR poster presentations are as follows:
Late-Breaking Poster Presentation
Title: Phase 2 trial of the NDC CRLX101 in combination with
Avastin® in patients with platinum-resistant Ovarian Cancer (PROC)
Date
and Time:
Abstract
number: CT090
Location: Section 13
Poster board
number: 18
Poster Presentations
Title: Tumor selective localization of CRLX101, an
investigational nanoparticle-drug conjugate of camptothecin
Date
and time:
Abstract
number: 1345
Location: Section 20
Poster board
number: 4
Summary: CRLX101, an investigational
nanoparticle-drug conjugate (NDC) containing the payload camptothecin,
is currently being evaluated in multiple treatment-refractory solid
tumors. In preclinical models, CRLX101 has demonstrated its ability to
release camptothecin in the tumor in a slow and prolonged manner due to
its long circulation half-life, and has shown striking anti-tumor
activity in several different tumor models. This study sought to
mechanistically dissect the process of CRLX101's entry and accumulation
into tumor cells. In this study, researchers demonstrate that
macropinocytosis and activation of actin polymerization play a role in
the process by which tumor cells take up CRLX101. Using confocal
microscopy, researchers were able to detect camptothecin fluorescence in
CRLX101-treated tumor cells that co-localize with intact nanoparticles,
and were able to visualize the distance traversed by CRLX101 from the
tumor vasculature over time. These data are an important step forward in
understanding the precise mechanism(s) underlying selective delivery of
CRLX101 into tumor tissue.
Title: Pharmacokinetics (PK) of CRLX301, a Novel
Nanoparticle-Drug Conjugate (NDC) Containing the Payload Docetaxel, in
Patients with Refractory Solid Tumors
Date and time:
Abstract number: 2047
Location:
Section 14
Poster board number: 19
Summary: CRLX301
is an investigational NDC containing the payload docetaxel. This study
evaluated CRLX301 PK in a phase 1 study in patients with refractory
solid tumors. CRLX301 was administered at 7.5, 15, 30, 60 and 75 mg/m2
IV over 1 h every 21 days. PK studies were performed and compared to a
prior PK study of Taxotere® at 75 mg/m2 IV x 1
every 21 days (Zamboni, et al. CCP 2011). The data suggest that CRLX301
exhibits PK advantages over Taxotere such as higher retention of drug in
plasma, slower clearance and controlled slow release of docetaxel from
the NDC. It is anticipated that this unique PK profile of CRLX301 may
improve efficacy and tolerance when compared to Taxotere. The study
continues with dose escalation to further explore the safety, efficacy
and PK of CRLX301.
Title: CRLX101, an investigational nanoparticle-drug conjugate of
camptothecin, demonstrates synergy with immunotherapy agents in
preclinical models
Date and time:
Abstract number: 3209
Location:
Section 25
Poster board number: 6
Summary: CRLX101
has been shown preclinically to be active in many different tumor types
as a dual inhibitor of topoisomerase 1 and hypoxia-inducible factor 1α
(HIF-1α), which is believed to control the expression of the
immune-suppressive molecule PD-L1. Since CRLX101 is a potent inhibitor
of HIF-1α, it is possible that it would behave as an inhibitor of the
PD-1/PD-L1 axis in vivo. This study sought to combine CRLX101
with agents that are being investigated in combination with the anti
PD-1 antibody to determine if increased efficacy could be observed.
Using syngeneic tumor models, Cerulean researchers tested the
combination of CRLX101 with three different IDO inhibitors (
Title: A camptothecin-containing nanoparticle-drug conjugate
combination with DDR agents provides a novel approach to increasing
therapeutic index
Poster presentation:
Abstract number: 3721
Location:
Section 14
Poster board number: 14
Summary: Topoisomerase
I inhibitors are used as standard-of-care chemotherapy in many types of
cancer but are associated with significant toxicities. There is
potential to improve their efficacy further by combining with a PARP
inhibitor, such as olaparib, but subsequent trials have shown dose
limiting myelotoxicity. This study explored the molecular mechanism and
therapeutic potential of combining CRLX101 with either olaparib or the
WEE1 inhibitor AZD1775, by testing efficacy and safety in preclinical
models. Collectively, these preclinical data demonstrate increased
anti-tumor efficacy of CRLX101 when combined with DDR inhibitors, while
mitigating much of the combined bone marrow toxicity through sequenced
schedules. The combination schedule for CRLX101 and olaparib identified
in Cerulean's preclinical models as providing an increased therapeutic
index has been used to develop clinical protocols to test this
combination in a second-line (relapsed) small cell lung cancer clinical
trial, which is being conducted in collaboration with the
Electronic copies of the posters will be available upon request following AACR by emailing [email protected].
About CRLX101
CRLX101 is a nanoparticle-drug conjugate (NDC) designed to concentrate
in tumors and slowly release its anti-cancer payload, camptothecin,
inside tumor cells. CRLX101 inhibits topoisomerase 1 (topo 1), which is
involved in cellular replication, and also inhibits hypoxia-inducible
factor-1α (HIF-1α), which research suggests is a master regulator of
cancer cell survival mechanisms. CRLX101 has shown activity in four
different tumor types, both as monotherapy and in combination with other
cancer treatments. CRLX101 is in Phase 2 clinical development and has
been dosed in more than 350 patients. The
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
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.
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including: the uncertainties inherent in the initiation of clinical
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or whether results of early clinical trials will be indicative of the
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Form 10-K filed with the
Avastin is a registered trademark of
Taxotere is a registered trademark of Sanofi and/or its consolidated subsidiaries.
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