Welcome!

News Feed Item

Threshold Announces Data From Ongoing Phase 1/2 Trial of TH-302 Plus Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

CHICAGO, IL -- (Marketwired) -- 05/30/14 -- Threshold Pharmaceuticals, Inc. (NASDAQ: THLD)

  • Preliminary clinical benefit rate of 31% (three partial responses and two minimal responses) in patients treated at the maximum-tolerated dose of TH-302 and low-dose dexamethasone

  • Objective responses observed in heavily pretreated patients including prior treatment with proteasome inhibitors [including carfilzomib (Kyprolis®)] and IMiDs [including pomalidomide (Pomalyst®)]

  • Enrollment completed at the previously established TH-302 maximum-tolerated dose (340 mg/m2)

  • Combination regimen of TH-302 and proteasome inhibitor bortezomib (Velcade®) to be investigated in final stage of ongoing trial

Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced new preliminary clinical data from an ongoing company-sponsored Phase 1/2 trial of its investigational hypoxia-activated prodrug, TH-302, in combination with low-dose dexamethasone in patients with relapsed/refractory multiple myeloma, a cancer of the bone marrow. The results are being presented today as part of the poster highlights session on Lymphoma and Plasma Cell Disorders at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago [Abstract #8534 (Poster #14)]. The data will also be discussed by clinical experts at Threshold's Analyst Event to be held Sunday, June 1, 2014, at 6:00 PM Central Time in Chicago and accompanied by a live webcast.

"Effective treatments for patients with advanced multiple myeloma who become refractory to current standards of care with proteasome inhibitors or immunomodulatory drugs (IMiDs) remains an area of exquisite unmet medical need," said Paul Richardson, M.D., Clinical Program Leader, Director of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, R.J. Corman Professor of Medicine, Harvard Medical School, Boston, Massachusetts. "The presence of hypoxia in the diseased bone marrow may present a new therapeutic target for treating multiple myeloma and underlies the rationale for evaluating hypoxia-targeted agents in this disease. In the limited number of patients treated, it is noteworthy that objective responses were observed in this heavily pretreated patient population, including patients who received prior therapy with a proteasome inhibitor (including carfilzomib) and an immunomodulatory agent (including pomalidomide), which are typically used in advanced and later stage multiple myeloma patients. Based on these early signals of clinical activity, we are looking forward to initiating the final stage of the ongoing trial in which patients will receive TH-302 and bortezomib, a combination that demonstrated synergistic activity in preclinical models of multiple myeloma."

The objectives of the ongoing Phase 1/2 trial include determining the safety and tolerability of TH-302 and dexamethasone, the dose-limiting toxicities and the maximum-tolerated dose of TH-302, and assessing preliminary signals of clinical activity in patients with relapsed/refractory multiple myeloma. The dose of TH-302 administered in the dose escalation portion of the study was 240, 340, or 480 mg/m2 (depending on the dose cohort into which a patient enrolled) given on days 1, 4, 8, and 11 of a 21-day cycle, with 40 mg dexamethasone given on the same days as TH-302. Previously, the maximum tolerated dose was reported to be 340 mg/m2 TH-302.1

Enrollment of patients with relapsed/refractory multiple myeloma in the dose-escalation and dose-expansion portions of the study is now complete, including 24 patients enrolled at the maximum tolerated dose of TH-302 (340 mg/m2). Patients had received a median of 6.5 systemic therapies prior to enrollment. The ASCO presentation includes data from 24 patients in the dose-escalation and dose-expansion portions of the study who initiated treatment prior to March 1, 2014; analyses reflect the clinical database as of May 19, 2014. Of these 24 patients, 17 were treated at the maximum tolerated dose of TH-302.

Key findings to be reported at ASCO are as follows:

Preliminary assessment of safety and tolerability

The most common adverse events related to TH-302 occurring in at least 25% of patients were nausea and fatigue. The most common Grade 3/4 hematologic adverse events related to TH-302 were thrombocytopenia (29%) and leukopenia (25%). Dose-limiting toxicities of Grade 3 stomatitis were reported during the first treatment cycle for the first two patients treated at 480 mg/m2 TH-302; therefore, the maximum tolerated dose of TH-302 was established at 340 mg/m2.

Preliminary assessment of clinical activity

Of the 24 patients included in the ASCO presentation, 23 were evaluable for response. According to modified International Myeloma Working Group (IMWG) criteria, best responses included four partial responses (4 PR), two minimal responses (2 MR), and 15 stable disease (15 SD) assessments; two patients had progressive disease (2 PD). The clinical benefit rate for patients treated at the maximum tolerated dose of TH-302 (n=16 evaluable patients) was 31% (comprised of 3 PR and 2 MR).

Poster Details

The poster titled, "Preliminary safety and efficacy of TH-302, an investigational hypoxia-targeted drug, and dexamethasone in patients with relapsed/refractory multiple myeloma" [Abstract #8534 (Poster #14)] is being presented at the Poster Highlights Session on Lymphoma and Plasma Cell Disorders, 1:00 PM - 4:00 PM Central Time, Friday, May 30, 2014, in Room S405; Discussion follows, 4:30 PM - 5:45 PM, Room S406.

Analyst Event with Clinical Experts on Sunday, June 1, 2014

Threshold will host an evening event for investors and analysts on Sunday, June 1, 2014, at 6:00 PM Central Time at the Four Seasons Hotel Chicago (120 East Delaware Place, Walton Room). The event will include presentations highlighting TH-302 data presented at ASCO. Guest speakers scheduled to give presentations include Dr. Paul G. Richardson, Clinical Program Leader, Director of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, R.J. Corman Professor of Medicine, Harvard Medical School, Boston, Massachusetts, and Dr. Andrew J. Brenner, Clinical Investigator with the Institute for Drug Development at the Cancer Therapy & Research Center at The University of Texas Health Science Center at San Antonio, Texas. RSVP to [email protected].

The event is open to investors and analysts. Threshold invites the public and the media to listen to the presentations via the live webcast, which will be available under Webcasts in the Investors section of www.thresholdpharm.com or can be accessed using the following link: http://psav.adobeconnect.com/thresholdpharmaceuticals/. The presentations are scheduled to begin at approximately 6:15 PM Central Time. A replay of the presentations will be archived on the site for 30 days.

About TH-302

TH-302 is an investigational hypoxia-activated prodrug that is designed to be activated under tumor hypoxic conditions, a hallmark of many cancers. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood supply as a result of aberrant vasculature. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic.

TH-302 is currently under evaluation in two Phase 3 trials: one in combination with doxorubicin versus doxorubicin alone in patients with soft tissue sarcoma, and the other in combination with gemcitabine versus gemcitabine and placebo in patients with advanced pancreatic cancer (MAESTRO). Both Phase 3 trials are being conducted under Special Protocol Agreements with the U.S. Food and Drug Administration (FDA). The FDA and the European Commission have granted TH-302 Orphan Drug Designation for the treatment of soft tissue sarcoma and pancreatic cancer. TH-302 is also being investigated in earlier-stage clinical trials of other solid tumors and hematological malignancies, in combination with chemotherapy and antiangiogenic therapy, and for certain cancers, is being investigated as a monotherapy.

Threshold has a global license and co-development agreement for TH-302 with Merck KGaA, Darmstadt, Germany, which includes an option for Threshold to co-commercialize in the U.S.

About Threshold Pharmaceuticals

Threshold Pharmaceuticals, Inc. is a biotechnology company focused on the discovery and development of drugs targeting tumor hypoxia, the low oxygen condition found in microenvironments of most solid tumors as well as the bone marrows of some hematologic malignancies. This approach offers broad potential to treat a variety of cancers. By selectively targeting tumor cells, we are building a pipeline of drugs that hold promise to be more effective and less toxic to healthy tissues than conventional anticancer drugs. For additional information, please visit our website (www.thresholdpharm.com).

Forward-Looking Statements

Except for statements of historical fact, the statements in this press release are forward-looking statements, including statements regarding the potential therapeutic uses and benefits of TH-302 and statements regarding the expected initiation of the final stage of the ongoing Phase 1/2 trial. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Potential risks and uncertainties include, but are not limited to: the ability of Threshold and Merck KGaA, Darmstadt, Germany, to enroll or complete TH-302 clinical trials; the time and expense required to conduct such clinical trials and analyze data; issues arising in the regulatory or manufacturing process and the results of such clinical trials (including product safety issues and efficacy results); the risk that preclinical studies in animal models of disease may not accurately predict the results of human clinical trials of TH-302; the risk that the final data from ongoing trials may be materially different from the preliminary data that Threshold has reported; Threshold's and Merck KGaA's (Darmstadt, Germany) dependence on single source suppliers, including the risk that these single source suppliers may be unable to meet clinical supply demands for TH-302 which could significantly delay the development of TH-302; risks related to Threshold's dependence on its collaborative relationship with Merck KGaA, Darmstadt, Germany, including its dependence on decisions by Merck KGaA, Darmstadt, Germany regarding the amount and timing of resource expenditures for the development of TH-302; and Threshold's need for and the availability of resources to develop TH-302 and to support Threshold's operations. Further information regarding these and other risks is included under the heading "Risk Factors" in Threshold's Quarterly Report on Form 10-Q, which has been filed with the Securities and Exchange Commission on May 1, 2014 and is available from the SEC's website (www.sec.gov) and on our website (www.thresholdpharm.com) under the heading "Investors." We undertake no duty to update any forward-looking statement made in this news release.

References

1. Ghobrial IM, et al. Phase 1 study of TH-302, an investigational hypoxia-targeted drug, and dexamethasone in patients with relapsed/refractory multiple myeloma Blood 122:1948, 2013.

More Stories By Marketwired .

Copyright © 2009 Marketwired. All rights reserved. All the news releases provided by Marketwired are copyrighted. Any forms of copying other than an individual user's personal reference without express written permission is prohibited. Further distribution of these materials is strictly forbidden, including but not limited to, posting, emailing, faxing, archiving in a public database, redistributing via a computer network or in a printed form.

Latest Stories
19th Cloud Expo, taking place November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy. Meanwhile, 94% of enterpri...
Kubernetes, Docker and containers are changing the world, and how companies are deploying their software and running their infrastructure. With the shift in how applications are built and deployed, new challenges must be solved. In his session at @DevOpsSummit at19th Cloud Expo, Sebastian Scheele, co-founder of Loodse, will discuss the implications of containerized applications/infrastructures and their impact on the enterprise. In a real world example based on Kubernetes, he will show how to ...
Personalization has long been the holy grail of marketing. Simply stated, communicate the most relevant offer to the right person and you will increase sales. To achieve this, you must understand the individual. Consequently, digital marketers developed many ways to gather and leverage customer information to deliver targeted experiences. In his session at @ThingsExpo, Lou Casal, Founder and Principal Consultant at Practicala, discussed how the Internet of Things (IoT) has accelerated our abil...
With so much going on in this space you could be forgiven for thinking you were always working with yesterday’s technologies. So much change, so quickly. What do you do if you have to build a solution from the ground up that is expected to live in the field for at least 5-10 years? This is the challenge we faced when we looked to refresh our existing 10-year-old custom hardware stack to measure the fullness of trash cans and compactors.
Extreme Computing is the ability to leverage highly performant infrastructure and software to accelerate Big Data, machine learning, HPC, and Enterprise applications. High IOPS Storage, low-latency networks, in-memory databases, GPUs and other parallel accelerators are being used to achieve faster results and help businesses make better decisions. In his session at 18th Cloud Expo, Michael O'Neill, Strategic Business Development at NVIDIA, focused on some of the unique ways extreme computing is...
The emerging Internet of Everything creates tremendous new opportunities for customer engagement and business model innovation. However, enterprises must overcome a number of critical challenges to bring these new solutions to market. In his session at @ThingsExpo, Michael Martin, CTO/CIO at nfrastructure, outlined these key challenges and recommended approaches for overcoming them to achieve speed and agility in the design, development and implementation of Internet of Everything solutions wi...
DevOps at Cloud Expo, taking place Nov 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 19th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is no time to wait for long dev...
Cloud computing is being adopted in one form or another by 94% of enterprises today. Tens of billions of new devices are being connected to The Internet of Things. And Big Data is driving this bus. An exponential increase is expected in the amount of information being processed, managed, analyzed, and acted upon by enterprise IT. This amazing is not part of some distant future - it is happening today. One report shows a 650% increase in enterprise data by 2020. Other estimates are even higher....
I wanted to gather all of my Internet of Things (IOT) blogs into a single blog (that I could later use with my University of San Francisco (USF) Big Data “MBA” course). However as I started to pull these blogs together, I realized that my IOT discussion lacked a vision; it lacked an end point towards which an organization could drive their IOT envisioning, proof of value, app dev, data engineering and data science efforts. And I think that the IOT end point is really quite simple…
Aspose.Total for .NET is the most complete package of all file format APIs for .NET as offered by Aspose. It empowers developers to create, edit, render, print and convert between a wide range of popular document formats within any .NET, C#, ASP.NET and VB.NET applications. Aspose compiles all .NET APIs on a daily basis to ensure that it contains the most up to date versions of each of Aspose .NET APIs. If a new .NET API or a new version of existing APIs is released during the subscription peri...
Today we can collect lots and lots of performance data. We build beautiful dashboards and even have fancy query languages to access and transform the data. Still performance data is a secret language only a couple of people understand. The more business becomes digital the more stakeholders are interested in this data including how it relates to business. Some of these people have never used a monitoring tool before. They have a question on their mind like “How is my application doing” but no id...
Identity is in everything and customers are looking to their providers to ensure the security of their identities, transactions and data. With the increased reliance on cloud-based services, service providers must build security and trust into their offerings, adding value to customers and improving the user experience. Making identity, security and privacy easy for customers provides a unique advantage over the competition.
Qosmos has announced new milestones in the detection of encrypted traffic and in protocol signature coverage. Qosmos latest software can accurately classify traffic encrypted with SSL/TLS (e.g., Google, Facebook, WhatsApp), P2P traffic (e.g., BitTorrent, MuTorrent, Vuze), and Skype, while preserving the privacy of communication content. These new classification techniques mean that traffic optimization, policy enforcement, and user experience are largely unaffected by encryption. In respect wit...
Using new techniques of information modeling, indexing, and processing, new cloud-based systems can support cloud-based workloads previously not possible for high-throughput insurance, banking, and case-based applications. In his session at 18th Cloud Expo, John Newton, CTO, Founder and Chairman of Alfresco, described how to scale cloud-based content management repositories to store, manage, and retrieve billions of documents and related information with fast and linear scalability. He addres...
Is the ongoing quest for agility in the data center forcing you to evaluate how to be a part of infrastructure automation efforts? As organizations evolve toward bimodal IT operations, they are embracing new service delivery models and leveraging virtualization to increase infrastructure agility. Therefore, the network must evolve in parallel to become equally agile. Read this essential piece of Gartner research for recommendations on achieving greater agility.