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Cascadian Therapeutics’ Lead Candidate, Tucatinib, Receives Orphan Drug Designation from FDA for Treatment of Breast Cancer Patients with Brain Metastases

On June 8, 2017 Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported that tucatinib, an investigational oral, small molecule kinase inhibitor that is highly selective for HER2 and the Company’s lead product in development, has been granted orphan drug designation by the U.S. Food and Drug Administration ("FDA") for the treatment of breast cancer patients with brain metastases (Press release, Cascadian Therapeutics, JUN 8, 2017, View Source [SID1234519473]).

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"Brain metastases arise in up to 50 percent of women with HER2-positive metastatic breast cancer and these metastases can compromise quality of life and survival," explained Eric P. Winer, MD, of Boston’s Dana-Farber Cancer Institute.

Winer’s colleague, Nancy U. Lin, MD, added, "Treatments for patients with brain metastases have been limited, and we urgently need new and more effective approaches."

"There remains an unmet medical need for patients with HER2-positive metastatic breast cancer, including patients whose disease has metastasized to the brain," said Scott Myers, President and CEO of Cascadian Therapeutics. "New treatment options are clearly needed and tucatinib is being developed to fit within the current and emerging treatment paradigm. Our ongoing registrational trial of tucatinib known as HER2CLIMB is enrolling patients with all types of brain metastases, including untreated, previously treated stable or progressing brain metastases. Approximately half of patients enrolled in HER2CLIMB to date have had brain metastases at study entry, which will allow us to assess activity in that subpopulation in a statistically meaningful way. We are encouraged by results from our ongoing Phase 1b combination study of tucatinib plus capecitabine and/or trastuzumab, which showed a 42 percent response rate in patients with HER2-positive brain metastases."

The FDA’s Orphan Drug Designation program provides orphan status to drugs defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the U.S. Orphan designation qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemption and 7-year marketing exclusivity upon FDA approval.

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 directed agents such as trastuzumab.1,2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, ovarian and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tumors that overexpress HER2 are more aggressive and historically have been associated with poor overall survival, compared with HER2-negative cancers.

About HER2CLIMB Pivotal Trial

HER2CLIMB is a randomized (2:1), double-blind, placebo-controlled pivotal clinical trial comparing tucatinib vs. placebo in combination with capecitabine and trastuzumab in patients with locally advanced or metastatic HER2-positive breast cancer who have had prior treatment with a taxane, trastuzumab, pertuzumab and ado-trastuzumab emtansine, also known as T-DM1. The primary endpoint is progression-free survival (PFS) based upon independent radiologic review. Key objectives related to assessing activity in brain metastases include a key secondary endpoint of PFS in a subset of patients with brain metastases. All patients will be followed for overall survival. HER2CLIMB is currently enrolling patients in the United States and Canada. Clinical sites in Western Europe, Australia and Israel are expected to open in the first half of 2017.

About HER2-Positive Metastatic Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. The American Cancer Society estimates that 20-25 percent of the approximately 246,660 annual new cases of breast cancer diagnoses in the U.S. are HER2-positive. Historically, HER2 disease has been associated with shorter survival times as well as a higher risk of recurrence and CNS disease (brain metastases). Approximately 30 to 50 percent of HER2-positive breast cancer patients develop brain metastases over time.3,4 Over the past two decades, the approvals of four targeted treatments (trastuzumab, pertuzumab, lapatinib, and T-DM1) have led to improved time to progression and survival rates of patients with HER2-positive breast cancer. Despite these advances, there is still a significant need for new therapies that can impact metastatic disease, including brain metastases, and be tolerated for longer periods of time.

AVEO Oncology Announces Phase 1/2 TiNivo Trial of Tivozanib and Opdivo® (nivolumab) in RCC Advances to Phase 2

On June 8, 2017 AVEO Oncology (NASDAQ:AVEO) reported that its Phase 1/2 AVEO-sponsored TiNivo trial evaluating tivozanib in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, Opdivo (nivolumab), in subjects with advanced renal cell carcinoma (RCC) has progressed to the Phase 2 portion of the trial (Press release, AVEO, JUN 8, 2017, View Source [SID1234519472]).

Advancement of the study into the Phase 2 expansion follows the successful completion of the Phase 1 dose escalation portion of the trial, where tivozanib was administered in two escalating dose cohorts in combination with nivolumab at a constant 240 mg every 2 weeks (n=6). The combination was well tolerated to the full dose and schedule of single agent tivozanib, with no dose limiting toxicities. The full dose tivozanib regimen of 1.5 mg daily for 21 days, followed by a 7 day rest period, is the recommended Phase 2 dose (RP2D) for the expansion portion of the trial, which is expected to enroll up to an additional 20 subjects. The TiNivo study is being led by the Institut Gustave Roussy in Paris under the direction of Bernard Escudier, MD, Chairman of the Genitourinary Oncology Committee. Phase 1 results from the ongoing study will be submitted for presentation at an upcoming scientific meeting.

"The promise of delivering synergistic activity by combining VEGF TKIs and PD-1s in renal cell carcinoma hinges on the tolerability of the combination," said Dr. Escudier. "Tivozanib has a uniquely favorable tolerability profile as demonstrated in past single agent and combination studies. These initial results are very promising in that we see both evidence of a uniquely tolerable combination as well as early and meaningful activity. I look forward to enrolling the expansion cohort and to establishing a broader understanding for the potential of this compelling combination."

"Together with the longest progression free survival from a Phase 3 first line RCC study, tivozanib’s tolerability is distinct from other VEGF TKIs, which we believe better position it for use in combination with immunotherapy and other agents," said Michael Bailey, president and chief executive officer of AVEO. "As our registration strategy for single agent tivozanib reaches key inflection points, with a European regulatory decision expected in the near-term and readout of our US registration-directed TIVO-3 study expected in the first quarter of 2018, our attention is increasing on tivozanib immuno-oncology combinations that have the potential to deliver significantly improved outcomes and tolerability to patients. The TiNivo trial is an important first step in this effort, and we share Dr. Escudier’s enthusiasm for the completion of this trial."

About Tivozanib

Tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.a

Midatech signs global license agreement to investigate panobinostat for treatment of brain cancers

On June 7, 2017 Midatech Pharma (AIM: MTPH; Nasdaq: MTP), the international specialty pharmaceutical company focused on commercialising and developing products in oncology, reported that it has signed a global licensing agreement with Novartis for the oncology compound panobinostat. Panobinostat will be developed by Midatech for the treatment of Diffuse Intrinsic Pontine Glioma (DIPG) as a continuation of its existing MTX110 program, and potentially for Glioblastoma (GBM) (Press release, Midatech Pharma, JUN 7, 2017, View Source [SID1234519676]).

In pre-clinical test models, panobinostat, which is a pan-HDAC inhibitor, demonstrated very high potency against DIPG tumour cell lines. In one such study panobinostat was the most effective of more than 80 anti-cancer agents tested.

Midatech’s MTX110 program is focused on the treatment of DIPG, a childhood brain cancer that is nearly always fatal, with a median survival of approximately 9 months. Using a technique called Convection Enhanced Delivery, MTX110 is infused directly into the brain tumour, and diffuses through and around it. This technique allows for elevated drug concentrations to be delivered to the tumour, while at the same time minimizing systemic toxicity and peripheral side-effects. MTX110 has been used to treat 5 patients to date in the USA and UK under its compassionate use program. In these patients MTX110 has been well tolerated thus far. We believe it holds promise as a potential therapeutic treatment for DIPG, for which there are currently no approved or effective therapies. Clinical studies in patients are planned to commence during 2017. Financial terms have not been disclosed.

Jim Phillips, CEO of Midatech Pharma, said: "In line with our strategy to focus on oncology and expand our product mix, we are pleased that Novartis recognises our unique capability to use their product panobinostat alongside our technology to treat orphan cancers. We look forward to driving it through development for treatment of DIPG, and make a real difference to the children suffering from this devastating and terminal disease."

MabVax Therapeutics ImmunoPET Imaging Agent MVT-2163 to be Featured in Two Presentations at the 2017 SNMMI Annual Meeting

On June 7, 2017 MabVax Therapeutics Holdings, Inc. (Nasdaq: MBVX), a clinical-stage biotechnology company with a fully human antibody discovery platform focused on the rapid translation into clinical development of products to address unmet medical needs in the treatment of cancer, reported that the Society of Nuclear Medicine and Molecular Imaging (SNMMI) has chosen MabVax’s immunoPET imaging agent, MVT-2163, for a podium presentation and a poster presentation at the upcoming annual meeting to be held in Denver, CO on June 10-14, 2017 (Press release, MabVax, JUN 7, 2017, View Source [SID1234519470]).

MabVax Therapeutics Logo (PRNewsfoto/MabVax Therapeutics Holdings, I)

The poster will be presented by Joseph O’Donoghue, Ph.D., Associate Attending Physicist, Department of Medical Physics at Memorial Sloan Kettering Cancer Center.

Poster Title: Biodistribution and radiation dose estimates for 89Zr-DFO-HuMab-5B1 (MVT-2163) in CA19-9 positive cancer: first-in-man results
Location: Hall C in the Colorado Convention Center, Denver Colorado
Session Date: Sunday, June 11, 2017
Time: 7:00 PM to 8:30 PM (CDT)

The podium presentation will be given by Lars Guenter Christian Lohrmann, M.D., Assistant Member and Assistant Attending Radiologist at Memorial Sloan Kettering Cancer Center, and lead investigator in the MVT-2163 Phase 1 clinical trial.

Title of Presentation: First-in-Human Study of 89Zr-DFO-HuMab-5B1 (MVT-2163) PET/CT imaging with and without HuMab-5B1 (MVT-5873) in patients with pancreatic cancer and other CA 19-9 positive malignancies
Location: Room 601 in the Colorado Convention Center, Denver Colorado
Session Date: Tuesday, June 13, 2017
Time: 8:10 AM (CDT)

These presentations will discuss the results of the Company’s Phase 1a dose-escalation and safety trial conducted in 12 patients with advanced pancreatic cancer. Both presentations will include PET scan images illustrating the utility of this novel immunoPET imaging agent and its potential role in preoperative staging of patients with pancreatic cancer.

BeiGene to Present Data on BGB-3111 at the 14th International Conference on Malignant Lymphoma and to Host Conference Call

On June 7, 2017 BeiGene, Ltd. (NASDAQ:BGNE), a clinical-stage biopharmaceutical company developing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported that it will present updates on its BTK inhibitor BGB-3111 in three oral presentations and a poster at the upcoming 14th International Conference on Malignant Lymphoma (14-ICML) (Press release, BeiGene, JUN 7, 2017, View Source [SID1234519469]). 14-ICML will take place June 14-17, 2017, in Lugano, Switzerland. Following its presentations, BeiGene will host an investor call and webcast to discuss the presented data and development program.

Oral Presentation, Abstract # 059

Title: Bruton’s Tyrosine Kinase (BTK) Inhibitor BGB-3111 Demonstrates High Very Good Partial Response (VGPR) Rate in Patients with Waldenström Macroglobulinemia (WM)

Presenter: Dr. Judith Trotman

Session: Session 4 – Targeting the BCR Pathways
Date & Time: Thursday, June 15, 2017, 4:00 PM CEST
Location: Room A, Cinema Corso and Aula Magna (Lugano University)

Oral Presentation, Abstract # OT06

Title: A Head-to-Head Phase 3 Study Comparing BGB-3111 and Ibrutinib in Patients with Waldenström Macroglobulinemia

Presenter: Dr. Christian Buske

Session: Ongoing Trials
Date & Time: Thursday, June 15, 2017, 6:05 PM CEST
Location: Auditorium (Lugano University)

Oral Presentation, Abstract # 103

Title: Safety and Activity of the Highly Specific BTK Inhibitor, BGB-3111 Plus Obinutuzumab in Patients (Pts) with Follicular Lymphoma (FL) and Chronic Lymphocytic Leukemia (CLL)

Presenter: Dr. Constantine Tam

Session: Session 7 – Advances in CLL
Date & Time: Friday, June 16, 2017, 11:50 AM CEST
Location: Room A, B, Marquee, Cinema Corso and Aula Magna (Lugano University)

Poster, Abstract # 237

Title: High Overall Response Rate with the BTK Inhibitor BGB-3111 in Patients with Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma: An Update on Safety and Activity

Presenter: Dr. John Seymour

Session Dates & Times: Wednesday, June 14, 12:30-6:30 PM CEST; Thursday, June 15, 8:30-6:30 PM CEST; Friday, June 16, 8:30-6:30 PM CEST
Location: Marquee

Investor Conference Call

Date & Time: Friday, June 16, 2017, 2:00 PM CEST (8:00 AM EDT, 8:00 PM China Standard Time)

Dial-in Numbers: 1-845-675-0437 or 1-866-519-4004 (US), 400-620-8038 or 800-819-0121 (China), +852 30186771 (Hong Kong), or +65 67135090 (International)

Conference ID Number: 33044427

A live webcast and replay will be available on BeiGene’s investor website, View Source The dial-in replay will be available approximately two hours after the conference and will be available for two days following the event. It can be accessed by dialing 1-646-254-3697 (US), 400-632-2162 (China), +852 30512780 (Hong Kong), or +61 2 8199 0299 (International).

About BGB-3111

BGB-3111 is a potent and highly selective investigational small molecule inhibitor of BTK. BGB-3111 has demonstrated higher selectivity against BTK than ibrutinib (the only BTK inhibitor currently approved by the U.S. Food and Drug Administration and the European Medicines Agency) based on biochemical assays, higher exposure than ibrutinib based on their respective Phase I experience, and sustained 24-hour BTK occupancy in both the blood and the lymph node.