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Actinium Pharmaceuticals Unveils Actimab-MDS and Planned Phase 2 Trial in Myelodysplastic Syndromes Targeted at Patients with High-Risk p53+ Genetic Mutations

On December 5, 2017 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company"), a clinical-stage biopharmaceutical company focused on developing and commercializing targeted therapies for safer myeloablation and conditioning of the bone marrow prior to a bone marrow transplant, and for the targeting and killing of cancer cells, reported Actimab-MDS, a new clinical initiative focused on myelodysplastic syndrome or MDS (Press release, Actinium Pharmaceuticals, DEC 5, 2017, View Source [SID1234522385]). Actimab-MDS is the latest clinical initiative from the Company’s CD33-Alpha Program, which combines the CD33 targeting ability of the antibody lintuzumab with the cell killing power of the alpha-particle emitting radioisotope Actinium-225. Actimab-MDS builds on the Company’s clinical development experience in over 100 patients and several clinical trials with Actimab-A for patients with acute myeloid leukemia (AML) and Actimab-M for patients with multiple myeloma (MM).

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Actinium, together with Dr. Roboz, will conduct a webcast at 8 AM ET on December 5, 2017 to introduce Actimab-MDS and the planned Phase 2 trial. Participants can register and view the webcast through the following link:

View Source

or via Actinium’s Investor Relations Calendar View Source

Participants may also participate by phone. The dial-in information is below:

Dial-in: U.S. (646) 402-9440

Dial-in: U.S./Canada (855) 698-6739

MDS occurs when the bone marrow produces stem cells that fail to mature to red blood cells, white blood cells or platelets. The only potentially curative treatment option for patients with MDS is a bone marrow transplant (BMT) also known as a hematopoietic stem cell transplant. Approximately 19% of MDS patients have a p53 genetic mutation. Data show that p53 mutation positive patients have shorter survival and poorer outcomes following a BMT as evidenced by shorter time to relapse and shorter Overall Survival (OS). The planned Phase 2 trial is intended to study Actimab-MDS as a conditioning regimen for patients with MDS and p53 mutations who will undergo a bone marrow transplant. Dr. Gail Roboz, Director of the Leukemia Program and Professor of Medicine at Weill Cornell New-York Presbyterian Hospital, will serve as principal investigator for the trial and lead a consortium of leading medical centers in the treatment of MDS that are expected to participate in the trial. The MDS Clinical Research Consortium members are the Cleveland Clinic, Dana-Farber Cancer Institute, Johns Hopkins, MD Andersen Cancer Center, Moffitt Cancer Center and Weill Cornell.

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "Actinium is delighted to be working with Dr. Roboz and the other members of the consortium. As our clinical experience using our CD33 antibody labelled with Actinium-225 has expanded, it has become evident that it has minimal extramedullary toxicities. We believe that this property would be beneficial in numerous indications as the broad expression of CD33 in various hematologic indications affords many opportunities for continued expansion of our CD33 program. Given the poor prognosis of MDS patients, particularly those with p53 mutations, we are committed to executing this trial for Actimab-MDS effectively in collaboration with Dr. Roboz and the consortium while forging an efficient regulatory pathway forward that will enable us to make this therapy available to patients as soon as possible."

Patients in the planned Phase 2 trial will receive 4.0 µCi/Kg administered via a single infusion 12 days prior to receiving their bone marrow transplant. Actinium has studied its CD33 antibody and Actinium-225 at this dose level in a previously completed Phase 1 clinical trial in acute myeloid leukemia. At this dose level the construct showed good tolerability with no extramedullary toxicities or side effects outside of the bone marrow. The myelosuppression effect of the construct at this dose level was strong and impacted all the treated subjects.

MDS or myelodysplastic syndrome is an Orphan Drug indication with an estimated prevalence of 60,000 patients in the US and 40,000 patients in the EU. Approximately nineteen percent of these patients test positive for a mutation of the p53 gene and these patients are considered high-risk in terms of their survival. Although bone marrow transplants can be curative or significantly extend survival for many MDS patients, those who are p53+ do not benefit as greatly and presence of the mutation is associated with significantly lower survival. It has been shown that approximately seventy-five percent of the MDS population expresses CD33 at expression levels greater than the twenty-five percent targeted in the Actimab-MDS trial. The addressable market for Actimab-MDS is expected to be in the neighborhood of fourteen thousand patients in the U.S. and EU combined with over eight thousand five hundred in the U.S.

Sandesh Seth, Actinium’s Chairman and CEO said, "Actimab-MDS aligns perfectly with Actinium’s strengths as we have significant expertise and know in the area of bone marrow transplant as a result of our experience with our pivotal Phase 3 program, Iomab-B. Looking forward, we believe there exists for Actinium a compelling revenue opportunity in the 2020-2021 timeframe by launching not one but possibly two therapies that can provide safer myeloablation with the potential for increasing curative outcomes from bone marrow transplant. Due to the involvement of Dr. Roboz and the MDS Clinical Research Consortium, we expect that the Actimab-MDS trial will benefit from their significant expertise; high patient volumes treated and defrayed costs. Due to these factors and with sufficient drug supply on hand, we expect trial costs in the low single-digit millions over the life of the trial most of which would be incurred in 2019, and after the anticipated milestones from our other trials. Bone marrow transplant remains a highly concentrated market with the top fifty centers performing a majority of the transplants and via our clinical development programs, we have already established a supply chain and presence in over twenty such centers that account for over 33% of the market. Having two novel therapies, serving two patient populations with high, unmet needs, would allow us to achieve scale and efficiency that we believe will unlock significant value. Actimab-MDS indeed has the potential to transform the outlook for the Company in a very positive manner and we look forward to discussing this program."

About Actimab-MDS

Actimab-MDS is Actinium’s third CD33 program with expected initiation of a Phase 2 clinical trial in 2018 for patients with Myelodysplastic Syndromes that have a p53 genetic mutation. MDS occurs when the bone marrow produces stem cells that fail to mature to red blood cells, white blood cells or platelets. The only potentially curative treatment option for patients with MDS is a bone marrow transplant (BMT), also known as a hematopoietic stem cell transplant. Approximately 19% of MDS patients have a p53 genetic mutation and it has been shown that p53 mutation positive patients have poorer survival and poorer outcomes following a BMT indicated by shorter time periods to relapse and shorter Overall Survival (OS).

Moleculin’s WP1066 Drug gets FDA Brain Tumor IND Clearance

On December 5, 2017 Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the MD Anderson Cancer Center ("MD Anderson"), reported the physician-sponsored Investigational New Drug ("IND") application for a Phase I trial of Moleculin’s drug WP1066 in patients with recurrent malignant glioma and brain metastasis from melanoma has been allowed by the US Food and Drug Administration ("FDA") (Press release, Moleculin, DEC 5, 2017, View Source [SID1234522382]).

"We are so pleased to now have a second drug enter the clinical stage," commented Walter Klemp, Chairman and CEO of Moleculin. "We believe WP1066 represents a new class of anticancer drugs able to fight tumors on two fronts by directly inhibiting cell signaling supporting tumor activity, and independently stimulating a natural immune response. This constitutes a new approach to treating brain tumors and tumor metastasis to the brain.

Mr. Klemp concluded, "Since the discovery of WP1066 at MD Anderson by Prof. Waldemar Priebe, it has now been studied by many independent groups and is widely recognized as a potent inhibitor of the activated form of a protein called STAT3, which has been implicated in many difficult to treat tumors, including brain tumors. Animal studies have shown that inhibition of STAT3 directly blocks tumor proliferation and its survival, while most importantly boosting the immune system’s ability to fight cancer. We finally have our first opportunity for a clinical proof of concept and confirmation of promising preclinical activity."
This IND was sponsored by Dr. Amy Heimberger, who will serve as the principal investigator for the Phase I trial at MD Anderson Cancer Center to evaluate safety and efficacy. Details about the trial can be viewed on www.clinicaltrials.gov.

Favorable Results from a Multi-Center Analysis of Delcath PHP Therapy to be Published in Journal of Surgical Oncology

On December 5, 2017 Delcath Systems, Inc. (OTCQB:DCTH), an interventional oncology company focused on the treatment of primary and metastatic liver cancers, announces that results of a multi-center retrospective analysis of Delcath’s PHP Therapy have been accepted for publication in the peer-reviewed Journal of Surgical Oncology (Press release, Delcath Systems, DEC 5, 2017, View Source;p=RssLanding&cat=news&id=2321097 [SID1234522379]). The study, Percutaneous Hepatic Perfusion with Melphalan in Uveal Melanoma: A Safe and Effective Treatment Modality in an Orphan Disease, was conducted by researchers from Moffitt Cancer Center in Tampa, FL and the University Hospital Southampton in the United Kingdom. The publication of the data is expected in an upcoming edition of the Journal. An abstract of this study was presented at the 12th Annual Regional Therapies International Symposium in Snowbird, Utah in February 2017.

Commenting on the announcement, Jennifer K. Simpson, Ph.D., President and CEO of Delcath Systems, said, "this study represents the largest data set outside of a controlled clinical trial on the use of PHP Therapy in the treatment of uveal melanoma metastatic to the liver. Preliminary results of the study presented at the Regional Therapies conference earlier this year showed data indicating tumor response and overall survival benefit with PHP Therapy beyond the 6-8 months seen with other therapies in this patient population. The most common serious side effects following treatment were anemia, thrombocytopenia and neutropenia; these were expected and the majority managed with supportive care. The preliminary data provide confidence that our Phase 3 clinical trial in ocular melanoma liver metastases can provide the evidence necessary to support an application for a labeled indication in this tumor type, and we look forward to the publication of the full study results."

PHP Therapy with Melphalan/HDS was developed by Delcath Systems as a targeted, whole organ therapy for the liver. It is commercially available as a device in Europe, where it is marketed as CHEMOSAT. The system has not been approved by the U.S. Food and Drug Administration, and is undergoing Phase 3 clinical testing in the U.S. as an investigational product.

IMBRUVICAÂ® (ibrutinib) Plus Rituximab Phase 3 iNNOVATE Trial in Rare WaldenstrÃ¶m’s Macroglobulinemia Met Primary Endpoint

On December 5, 2017 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported the Phase 3 iNNOVATE (PCYC-1127) trial evaluating IMBRUVICA (ibrutinib) in combination with rituximab in patients with treatment-naïve and previously-treated Waldenström’s macroglobulinemia (WM) successfully met its primary endpoint and demonstrated improvement of progression-free survival (PFS) compared to rituximab alone (Press release, AbbVie, DEC 5, 2017, View Source [SID1234522376]). The Independent Data Monitoring Committee (IDMC) recommended that the study be unblinded based on the positive outcome from the pre-specified interim analysis data. IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

"IMBRUVICA is the first and only treatment approved in Waldenström’s macroglobulinemia. We continue to be committed to exploring the full potential of IMBRUVICA, and are pleased to add the results of iNNOVATE to our growing scientific understanding of its use as a combination therapy in WM and other blood cancers," said Thorsten Graef, M.D., Ph.D., Head of Clinical Development at Pharmacyclics LLC, an AbbVie company.

Pharmacyclics and Janssen are planning to share the interim analysis data from the study with regulatory authorities and plan to present the data in a future publication or medical congress. In January 2015, the U.S. FDA granted approval for IMBRUVICA for adult patients with WM. The approval was supported by the FDA’s Breakthrough Therapy Designation.

"This is a first-of-its-kind prospective randomized trial in Waldenström’s macroglobulinemia," said Meletios A. Dimopoulos, M.D., Professor and Chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine. "The full report of this study will be of important clinical significance regarding the benefits of the combination of ibrutinib with rituximab in patients with WM."

WM is a rare form of non-Hodgkin’s lymphoma, and roughly 1,000 to 1,500 people are diagnosed each year in the U.S.1

Zymeworks Presents Results of the Completed Dose Escalation Portion of the Ongoing Phase 1 Study of ZW25 at the San Antonio Breast Cancer Symposium

On December 5, 2017 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company dedicated to the development of next-generation multifunctional biotherapeutics, reported the completed dose escalation portion of its Phase 1 study of ZW25, a novel Azymetric bispecific antibody targeting two distinct domains of the HER2 receptor (Press release, Zymeworks, DEC 5, 2017, View Source [SID1234522372]). The HER2–mediated signaling pathway is believed to contribute to tumor growth in a number of cancers.

A total of 22 patients have been enrolled in the study, including 11 with breast cancer, eight with gastric, gastroesophageal junction, or esophageal (GE) cancer, and three with other HER2-expressing cancers. Part one of the multi-part study was a standard dose escalation where patients received ZW25 either weekly at 5 mg/kg (n=3), 10 mg/kg (n=6), or 15 mg/kg (n=7) or bi-weekly (once every two weeks) at 20 mg/kg (n=6) in cycles of four weeks each.

Study Highlights:

Six Partial Responses (PR) were observed across all dosing groups including two new PRs from the 20 mg/kg bi-weekly cohort.

Clinical benefit (Confirmed PR or stable disease (SD) ≥ 6 months) of single agent ZW25 observed in heavily pretreated HER2-high breast and GE cancer patients.

Breast cancer patients received a median of six prior HER2-targeted regimens for metastatic disease; partial response in 56% (5/9) of breast cancer patients with measurable disease, with 89% (8/9) experiencing a decrease in target lesions.

Three HER2-high GE cancer patients with measurable disease showed tumor shrinkage, including one Confirmed PR (71% decrease in target lesions) and one SD for > 6 months.

ZW25 was well-tolerated at all doses and schedules, with the most common adverse events being diarrhea, infusion reactions, or nausea, all Grade 1 or 2 in severity.

The dose escalation portion of the Phase 1 trial is complete and enrollment in the expansion cohorts is underway.
Seventy-nine percent of breast and GE cancer patients with measurable disease (11/14) had a decrease in target lesions per RECIST criteria. The best overall response (BOR) in 17 response-evaluable (defined as undergoing at least one tumor restaging) breast and GE cancer patients was six PR (35%), three SD (18%) and eight progressive disease (PD; 47%).

"The expanding dataset continue to show responses and durable disease control with both weekly and every other week dosing and demonstrate the potential of ZW25 to address unmet need across multiple indications," said Dr. Diana Hausman, Chief Medical Officer of Zymeworks. "We are seeing meaningful clinical benefit with single agent treatment in breast and gastric cancer patients who have progressive disease after numerous standard of care regimens. These early results, while impressive in their own right, are also distinct from other investigational agents being evaluated in refractory HER2-expressing cancer patients and support the continued evaluation of ZW25 both as a single agent and in combination with other cancer therapeutics."

Of the eleven breast cancer patients, all were HER2-high and had received a median of six prior HER2-targeted regimens for metastatic disease including trastuzumab (n=11), T-DM1 (n=11), pertuzumab (n=9), and lapatinib (n=7) as well as other investigational agents. The BOR in these heavily pretreated patients was five PR (45%), two SD (18%), and three PD (27%), for an overall disease control rate (Complete Response, PR, or SD) of 64%. At least one PR was observed in every dosing group.

Of the eight GE patients, six were evaluable for response, and had received a median of four prior systemic regimens, including trastuzumab in all patients. Three of five patients with measurable disease had a decrease in tumor size, including one patient continuing on treatment with a Confirmed PR and 71% decrease in target lesions, as well as a second patient with SD for over 6 months.

"There is an ongoing need for novel treatments for patients who have exhausted available options for their HER2-expressing cancers," said Dr. Erika Hamilton, Director of the Breast Cancer and Gynecologic Cancer Research Program at Sarah Cannon Research Institute in Nashville, Tennessee. "The preliminary anti-tumor activity and tolerability we have seen with single agent ZW25 has been encouraging. We are excited to be enrolling patients in the expansion cohort portion of this study."

Enrollment is underway for the second part of the study utilizing ZW25 every other week at 20 mg/kg in four expansion cohorts spanning HER2-high breast, HER2-high gastric, HER2-intermediate breast and other HER2-gene amplified cancers.

"The dose escalation portion of the Phase 1 trial has been a success, demonstrating the tolerability and single agent anti-tumor activity of ZW25," said Dr. Ali Tehrani, President and CEO of Zymeworks. "These data bring us one step closer to initiating a single agent registrational trial with the goal of submitting an initial Biologics License Application (BLA) for ZW25 in 2021. We plan to provide an update on the expansion cohort portion of the trial at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in 2018."

The poster will be formally presented on Friday December 8th from 5:00-7:00pm CT at the San Antonio Breast Cancer Symposium and is available through their website or through the Investor page of Zymeworks’ website at View Source

ZW25 Phase 1 Clinical Trial Details

The dose escalation portion of the study enrolled 22 patients with HER2-expressing cancers (either HER2 IHC 1+, 2+ or 3+, or FISH-positive) whose cancer had progressed after treatment with all therapies known to confer clinical benefit. HER2 status was assessed in archived or fresh biopsies locally and at a central laboratory. Patients with HER2-high breast cancer (HER2 IHC 3+ or IHC2+ and FISH-positive) had to have received previous treatment with trastuzumab, pertuzumab, and T-DM1. Patients with HER2-high gastric or gastroesophageal cancers had to have been previously treated with trastuzumab. Patients could have measurable or non-measurable tumor lesions per RECIST 1.1. Patients with known active brain metastases were excluded from the study. Patients were assessed during treatment for safety, including changes in cardiac function, tumor response per RECIST 1.1 every 8 weeks, ZW25 drug levels, and potential development of anti-drug antibodies. No dose-limiting toxicities were seen at any dose level or schedule. The most common adverse events were diarrhea, infusion reactions, or nausea, all Grade 1 or 2 in severity. There were no treatment-related serious adverse events, cardiac events or decreases in left ventricular ejection fraction.

About ZW25

ZW25 is Zymeworks’ lead product candidate currently being evaluated in a Phase 1 clinical trial in the United States. It is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function and has led to significant anti-tumor activity in preclinical models of HER2-expressing cancer. Zymeworks is developing ZW25 as a best-in-class HER2-targeted treatment option for patients with any solid tumor that expresses HER2.