Press Release Details
Deciphera Pharmaceuticals Announces Positive, Preliminary, Top-Line Clinical Data for the Ongoing Phase 1 Clinical Study with DCC-3014 and an Update on Future Development Plans
- DCC-3014, A Highly-Selective and Potent Small Molecule Inhibitor of CSF1R, Demonstrates Tolerability, Pharmacokinetics and Biomarker Mechanistic Proof-of-Concept (mPoC) in Patients with Advanced Malignancies -
- Deciphera Pharmaceuticals Plans Expansion of Ongoing Phase 1 Study to Include Patients with Tenosynovial Giant Cell Tumors -
The Phase 1 study was designed to evaluate the safety, pharmacokinetics and pharmacodynamics of multiple doses of DCC-3014 in up to 55 patients.
As of the data cut-off date of
November 9, 2018, increasing doses of DCC-3014 were assessed in five dose cohorts across 24 patients with advanced solid tumor malignancies. This included one dose cohort that received 10 mg once daily (QD) and four dose cohorts that followed a schedule of once or twice-weekly maintenance dosing preceded by a five-day loading dose regimen at doses of up to 30 mg per dose. In addition, four patients are currently enrolled in a dose cohort that will receive 40 mg twice weekly preceded by a five-day loading regimen.
- Preliminary pharmacokinetic (PK) analysis showed dose-proportional exposure for DCC-3014 that we believe supports twice-weekly maintenance dosing preceded by a five-day loading dose regimen.
- Biomarker data demonstrated strong target engagement of CSF1R, including material reductions in CSF1R positive macrophages in the blood that we believe constitutes mechanistic proof-of-concept (mPoC) for DCC-3014.
DCC-3014 was generally well tolerated in patients enrolled in the dose
cohorts that received twice-weekly maintenance doses of DCC-3014
preceded by a five-day loading regimen at doses of up to 30 mg, which
is summarized below:
- Treatment emergent adverse events (TEAEs) were mostly Grade 1 or 2;
- No Grade 3 or 4 DCC-3014 related TEAEs in ≥10% of patients;
- No dose-limiting toxicities; and
- A maximum tolerated dose has yet to be established.
- In the dose-cohort that received 10 mg QD, clinically asymptomatic laboratory values were recorded as dose-limiting toxicities in two of seven patients.
“We are very pleased with the progress made to date in the Phase 1
clinical study with DCC-3014, our selective, and potent small molecule
inhibitor of CSF1R,” said
DCC-3014 is an investigational, orally administered, potent and highly selective inhibitor of CSF1R. DCC-3014 was designed using the Company’s proprietary switch control kinase inhibitor platform to selectively bind to the CSF1R switch pocket. DCC-3014 has greater than 100-fold selectivity for CSF1R over the closely related kinases FLT3, KIT, PDGFRα, PDGFRß and VEGFR2 and has an even greater selectivity for CSF1R over approximately 300 other human kinases. CSF1R controls the differentiation and function of macrophages including Tumor Associated Macrophages (TAMs) whose density within certain tumors including cancers of the breast, cervix, pancreas, bladder and brain correlates with poor prognosis. Tumors induce TAMs to suppress a natural immune response mediated by cytotoxic T-cells, a type of lymphocyte that would otherwise eradicate the tumor; a process known as macrophage checkpoints. Through inhibition of CSF1R DCC-3014 has in preclinical studies demonstrated potent macrophage checkpoint inhibition as both a single agent and in combination with PD1 inhibitors and other T-cell checkpoint inhibitors. DCC-3014 is currently being evaluated in a Phase 1 clinical study. For more information about the clinical trial design please visit www.clinicaltrials.gov (NCT03069469).
About Tenosynovial Giant Cell Tumors (TGCTs)
Tenosynovial giant cell tumors (TGCTs) are a group of benign tumors that involve the synovium, bursae and/or tendon sheath. Although benign, these tumors can grow and cause damage to surrounding tissues and structures inducing pain, swelling, and limitation of movement of the joint. Surgery is the main treatment option; however, these tumors tend to recur, particularly in pigmented villonodular synovitis, a diffuse-type of TGCT. If untreated or if the tumor continually recurs damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability. A genetic mutation in certain cells within the tumor causes overproduction of CSF-1, the ligand for the CSF1R receptor, which attracts macrophages and certain other cells that become the bulk of these tumors and cause the associated inflammatory changes.
Investors and others should note that
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995, as
amended, including, without limitation, statements regarding our
expectations regarding our clinical trials with our investigational
agent DCC-3014, including, without limitation, the potential for
DCC-3014 as an effective and well tolerated therapy, the plan to present
data at a medical meeting in 2019, the timing of and plan for expansion
of the Phase 1 clinical study with DCC-3014 to include patients with
TGCT and the timing of and plan to explore combinations with other
therapies. The words “may,” “will,” “could,” “would,” “should,”
“expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,”
“predict,” “project,” “potential,” “continue,” “target” and similar
expressions are intended to identify forward-looking statements,
although not all forward-looking statements contain these identifying
words. Any forward-looking statements in this press release are based on
management’s current expectations and beliefs and are subject to a
number of risks, uncertainties and important factors that may cause
actual events or results to differ materially from those expressed or
implied by any forward-looking statements contained in this press
release, including, without limitation, risks and uncertainties related
to the delay of any current or planned clinical studies or the
development of our drug candidates, including DCC-2618, rebastinib, and
DCC-3014, our advancement of multiple early-stage and later-stage
efforts, our ability to successfully demonstrate the efficacy and safety
of our drug candidates including in later-stage studies, the preclinical
and clinical results for our drug candidates, which may not support
further development of such drug candidates, our efforts to scale up
drug product manufacturing, our ability to implement commercial
readiness, actions of regulatory agencies, any or all of which may
affect the initiation, timing and progress of clinical studies and other
risks identified in our
Gina Nugent, The Yates Network
Christopher J. Morl, Chief Business Officer
Deciphera Pharmaceuticals, LLC