Celldex Therapeutics, Inc. (NASDAQ:CLDX) today presented
results from the CDX-3379 clinical program at the 2019 American
Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. To
date, three studies of CDX-3379 have enrolled patients with head
and neck squamous cell carcinoma (HNSCC), including the ongoing
Phase 2 exploratory study of CDX-3379 in combination with Erbitux®
(cetuximab) in patients with cetuximab-resistant, advanced
human papillomavirus (HPV) negative HNSCC who have previously been
treated with an anti-PD1 checkpoint inhibitor.
Emerging data from the Phase 2 study and earlier studies of
CDX-3379 suggest that antitumor activity may be associated with
somatic mutations in certain genes. Based on these observations,
Celldex conducted an exploratory biomarker analysis in 18 HNSCC
patients across the CDX-3379 clinical development program. These
results support the further development of CDX-3379 in
biomarker-selected patient populations and were highlighted during
a presentation at ASCO by Julie E. Bauman, MD, MPH, Professor of
Medicine, Chief, Division of Hematology and Oncology, Associate
Director, Translational Research, University of Arizona Cancer
Center, lead author for the poster and an investigator in the Phase
2 study.
“We have observed intriguing clinical activity across a number
of patients with similar gene mutation patterns in a disease that
has extremely limited treatment options and a particularly poor
prognosis,” said Dr. Bauman. “While the data are early, they are
provocative and suggest the potential for a biomarker enrichment
strategy that could change the standard of care for these patients.
I look forward to the opportunity to obtain additional data on
CDX-3379 in biomarker selected patient
populations.”
CDX-3379 is a human monoclonal antibody that uniquely blocks the
activity of ErbB3 (HER3). ErbB3 is expressed in many cancers,
including head and neck squamous cell cancer (HNSCC) and is
believed to be an important receptor regulating cancer cell growth
and survival as well as resistance to targeted therapies.
Biomarker analysis
Next-generation sequencing was performed on tumor samples from
18 patients with HNSCC treated with CDX-3379 across the three
clinical studies. This data set included four patients with
clinical responses, including two durable complete responses (11+
months and 8.3 months), an exceptional partial response (greater
than 92% tumor shrinkage) and an unconfirmed partial response;
eight patients with stable disease and/or tumor shrinkage; and, six
patients with progressive disease.
- Across the CDX-3379 program, FAT1 and NOTCH1, NOTCH2, or NOTCH3
mutations and primary tumor site of oral cavity were associated
with clinical activity (clinical response, tumor shrinkage and
stable disease) in HNSCC
- All four clinical responses occurred in patients with FAT1
mutations
- All four clinical responses occurred in patients with a primary
tumor site of oral cavity
- Three of the four clinical responses occurred in patients who
also had NOTCH1, NOTCH2 or NOTCH3 mutations
- Also, of note, all patients (n=7 of 18) who experienced
clinical benefit (objective response or stable disease greater than
or equal to 12 weeks) had FAT1 and/or NOTCH1-3 mutations.
- Current literature suggests that loss of FAT1 function results
in activation of the transcriptional cofactor YAP11; YAP1 has been
shown to upregulate components of ErbB signaling pathways2,3,
including the ErbB3 ligand NRG14
- Inactivating mutations in the FAT1 and NOTCH genes have been
identified in 32% and 26% of HPV(-) HNSCC tumors,
respectively5
- Preclinical studies investigating the association of CDX-3379
sensitivity and inactivating mutations of FAT1 and other genes are
ongoing
Phase
2 CDX-3379 Study Results and Next
Steps This
multicenter, open-label, Phase 2 study of CDX-3379 in combination
with cetuximab is designed to enroll approximately 30 patients with
cetuximab-resistant, advanced, HPV negative HNSCC who have
previously been treated with an anti-PD1 checkpoint inhibitor, a
population with limited options and a particularly poor prognosis.
Cetuximab is dosed weekly (initial dose at 400 mg/m2 IV, then 250
mg/m2 IV); CDX-3379 (12 mg/kg IV) is administered once every three
weeks. Treatment continues until disease progression or
intolerance, and assessments occur every six weeks. Using a Simon
two-stage design, the first stage of study was designed to enroll
13 patients, and if at least one patient achieved a partial
response or complete response, enrollment could progress to the
second stage; this objective was met.
Fifteen patients were enrolled in stage 1 of the study. Patients
had a median of 3 (range of 2-6) prior cancer therapy treatments.
All patients had received prior checkpoint inhibitor treatment and
14 of 15 patients were cetuximab refractory. Notable clinical
activity was observed in this refractory patient population where
treatment options are limited.
- A durable confirmed complete response (11+ months) was
observed; this response remains ongoing and the patient continues
to receive treatment.
- An unconfirmed partial response (uPR) in a patient that had not
received cetuximab was also observed.
- 7 patients experienced stable disease (47%; includes uPR).
- A clinical benefit rate of 29% was achieved (objective response
or stable disease greater than or equal to 12 weeks).
- Dose reductions and/or delays to the combination therapy in the
majority of patients may have impacted the magnitude of anti-tumor
activity; dose modifications are being considered for future
studies.
- CDX-3379 in combination with cetuximab was generally associated
with the expected target-mediated adverse events of diarrhea and
rash.
Celldex intends to incorporate evaluation of biomarkers for
patient selection into the CDX-3379 development program, either
through amending the existing study or concluding the study and
initiating a new clinical trial. The Company, working together with
investigators and key opinion leaders in the treatment of HNSCC,
anticipates finalizing these plans in the coming weeks.
Erbitux® is a registered trademark of Eli Lilly & Co.1Martin
D, Nat Commun 2018. 2Zhang J, Nat Cell Biol 2009. 3Wang C, Cancer
Res 2017. 4He C, Oncogene 2015. 5Cancer Genome Atlas Network,
Nature 2015.
About CDX-3379CDX-3379 is a human
immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that
selectively binds and inhibits ErbB3 activity. ErbB3 may be an
important receptor regulating cancer cell growth and survival as
well as resistance to targeted therapies, and it is expressed in
many cancers, including head and neck, thyroid, breast, lung and
gastric cancers, as well as melanoma. The proposed mechanism of
action for CDX-3379 sets it apart from other drugs in development
in this class due to its ability to block both ligand-independent
and ligand-dependent ErbB3 signaling by binding to a unique
epitope. It has a favorable pharmacologic profile, including a
longer half-life and slower clearance relative to other drug
candidates in this class. CDX-3379 also has potential to enhance
anti-tumor activity and/or overcome resistance in combination with
other targeted and cytotoxic therapies to directly kill tumor
cells.
About Celldex Therapeutics, Inc.Celldex is
developing targeted therapeutics to address devastating diseases
for which available treatments are inadequate. Our pipeline
includes immunotherapies and other targeted biologics derived from
a broad set of complementary technologies which have the ability to
engage the human immune system and/or directly inhibit tumors to
treat specific types of cancer or other diseases. Visit
www.celldex.com.
Forward Looking StatementThis release contains
"forward-looking statements" made pursuant to the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
These statements are typically preceded by words such as
"believes," "expects," "anticipates," "intends," "will," "may,"
"should," or similar expressions. These forward-looking statements
reflect management's current knowledge, assumptions, judgment and
expectations regarding future performance or events. Although
management believes that the expectations reflected in such
statements are reasonable, they give no assurance that such
expectations will prove to be correct or that those goals will be
achieved, and you should be aware that actual results could differ
materially from those contained in the forward-looking statements.
Forward-looking statements are subject to a number of risks and
uncertainties, including, but not limited to, our ability to
successfully complete research and further development and
commercialization of Company drug candidates; our ability to obtain
additional capital to meet our long-term liquidity needs on
acceptable terms, or at all, including the additional capital which
will be necessary to complete the clinical trials that we have
initiated or plan to initiate; our ability to maintain compliance
with Nasdaq listing requirements; our ability to realize the
anticipated benefits from the acquisition of Kolltan; the
uncertainties inherent in clinical testing and accruing patients
for clinical trials; our limited experience in bringing programs
through Phase 3 clinical trials; our ability to manage and
successfully complete multiple clinical trials and the research and
development efforts for our multiple products at varying stages of
development; the availability, cost, delivery and quality of
clinical and commercial grade materials produced by our own
manufacturing facility or supplied by contract manufacturers, who
may be our sole source of supply; the timing, cost and uncertainty
of obtaining regulatory approvals; the failure of the market for
the Company's programs to continue to develop; our ability to
protect the Company's intellectual property; the loss of any
executive officers or key personnel or consultants; competition;
changes in the regulatory landscape or the imposition of
regulations that affect the Company's products; and other factors
listed under "Risk Factors" in our annual report on Form 10-K and
quarterly reports on Form 10-Q.
All forward-looking statements are expressly qualified in their
entirety by this cautionary notice. You are cautioned not to place
undue reliance on any forward-looking statements, which speak only
as of the date of this release. We have no obligation, and
expressly disclaim any obligation, to update, revise or correct any
of the forward-looking statements, whether as a result of new
information, future events or otherwise.
Company ContactSarah CavanaughSenior Vice
President, Corporate Affairs & AdministrationCelldex
Therapeutics, Inc.(781) 433-3161scavanaugh@celldex.com
Celldex Therapeutics (NASDAQ:CLDX)
Historical Stock Chart
From Mar 2024 to Apr 2024
Celldex Therapeutics (NASDAQ:CLDX)
Historical Stock Chart
From Apr 2023 to Apr 2024