Isis Pharmaceuticals, Inc. ISIS announced that data from the Phase 1 study of ISIS-STAT3[Rx] in
patients with cancer were presented today at the American Society of Clinical
Oncology in Chicago. Results of the initial dose escalation study in patients
with metastatic cancer showed that ISIS-STAT3[Rx] treatment resulted in
partial responses that were durable and prolonged in two out of three patients
with diffuse large B-cell lymphoma (DLBCL) who were refractory to prior
chemotherapy treatments. Isis and AstraZeneca are currently evaluating
ISIS-STAT3[Rx], in two clinical studies in patients with advanced lymphoma and
metastatic liver cancer.
"STAT3 activation has been shown to be associated with the growth,
invasiveness and metastases of many types of cancer making it an attractive
anti-cancer target. However, STAT3 has proven to be a difficult target to
inhibit. ISIS-STAT3[Rx] is one of the new molecules in development that
inhibit STAT3," said David S. Hong, M.D., associate professor, department of
investigational cancer therapeutics at the University of Texas MD Anderson
Cancer Center. "Patients with advanced cancer often have failed multiple
therapies and have few other chemotherapeutic options. For these patients
there is a desperate need for new therapies that can halt their disease
progression. The clinical responses observed to date suggest that inhibition
of STAT3 could provide benefit to some of these cancer patients. The early
clinical data on ISIS-STAT3[Rx ]is impressive because it suggests that this
drug can produce durable responses in patients with advanced cancer who have
failed to respond to other therapies."
ISIS-STAT3[Rx], also referred to as AZD9150, is the first drug in Isis'
pipeline that incorporates Isis' Generation 2.5 chemistry, which Isis
developed to increase potency of antisense drugs, thereby creating
opportunities for drugs like ISIS-STAT3[Rx] to be effective in more
difficult-to-treat cancers, like DLBCL. The open-label, dose-escalation Phase
1 study evaluated ISIS-STAT3[Rx] in 15 patients with advanced solid tumors and
lymphoma who had relapsed or were refractory to multiple chemotherapy
regimens. Signals of tumor responses were observed in four patients, including
objective partial responses in two of three patients with DLBCL. One patient
with a partial response with DLBCL, who had previously failed ten different
chemotherapy regimens, experienced a 50 percent reduction in tumor burden and
has maintained a partial response for longer than one year and continues to
receive weekly ISIS-STAT3[Rx] therapy. Another patient with DLBCL
experienced a partial response with a 65 percent reduction in tumor burden
and, as a result, was well enough to receive an autologous stem cell
transplant. This patient successfully completed a bone marrow transplant and
remains disease free. Isis and AstraZeneca are currently evaluating
ISIS-STAT3[Rx] in two other clinical studies, including a study in patients
with advanced lymphomas, like DLBCL, and a study in patients with advanced
metastatic hepatocellular carcinoma.
"AstraZeneca's considerable expertise in developing anti-cancer drugs has
enabled us to rapidly advance the clinical development of ISIS-STAT3[Rx]. We
believe that ISIS-STAT3[Rx] may be applicable to many different types of
cancer. As such, together with AstraZeneca, we plan to evaluate
ISIS-STAT3[Rx] in a broad Phase 2 program," said Brett Monia, Ph.D., senior
vice president, antisense drug discovery at Isis. "We are very pleased and
encouraged with the safety and efficacy observed in our initial clinical study
of ISIS-STAT3[Rx] and look forward to the results from the two ongoing
clinical studies in patients, which we plan to report next year."
ISIS-STAT3[Rx] is designed to inhibit the production of signal transducer and
activator of transcription 3 (STAT3), a protein critical for tumor cell growth
and survival. In addition, STAT3 is an important mediator of signaling in the
JAK2/STAT3 pathway, which has been previously shown to be an important target
for drug development. Because STAT3 is activated in numerous types of cancer,
ISIS-STAT3[Rx] has the potential to be broadly useful for both solid and
hematologic tumors. ISIS-STAT3[Rx] has been shown to reduce STAT3 levels in
preclinical tumor models and produce anti-tumor activity. Inhibition of STAT3
has also been shown to block the induction of tumor-associated cytokines
involved in the progression of cancer, such as IL-6, IL-1, TGF, and IL-10,
which could serve as important biomarkers in clinical studies.
Market News and Data brought to you by Benzinga APIs© 2024 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.
Comments
Loading...
Posted In: News
Benzinga simplifies the market for smarter investing
Trade confidently with insights and alerts from analyst ratings, free reports and breaking news that affects the stocks you care about.
Join Now: Free!
Already a member?Sign in