On December 1, 2014 Calithera Biosciences presented the corporate presentation (Presentation, Calithera Biosciences, DEC 1, 2014, View Source [SID1234535305]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On December 1, 2014 Unum Therapeutics, a company developing a universal cellular immunotherapy to treat multiple cancers, announced today that recruitment has begun in the first clinical trial of the ATTCK20 therapy (Press release, Unum Therapeutics, DEC 1, 2014, View Source!2014dec01-unum-starts-phase-1/cyn5 [SID:1234505419]). The Phase I study will examine the feasibility, safety and potential efficacy of infusing the ATTCK20 combination therapy in patients with B-cell malignancies and persistent disease following standard therapy. The clinical program commences shortly after the company’s official launch in October 2014.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Despite recent advances in cancer treatments, there are still far too many individuals with B-cell malignancies who die from their disease," said Chuck Wilson, PhD, President & CEO of Unum Therapeutics. "With these unmet medical needs fueling our efforts, we are excited to see the start of clinical testing for ATTCK20. This novel therapy leverages two of the strongest immunotherapy technologies in modern medicine – engineered T-cells and monoclonal antibodies – to target cancer."

ATTCK20 Clinical Trial

Antibody-Targeted Tumor Cell Killing (ATTCK) happens when T-cells expressing an antibody-coupled T-cell receptor (ACTR) engage a tumor-targeting antibody on the surface of a cancer cell. ATTCK20 is a combination of a patient’s ACTR T-cells administered with rituximab, a monoclonal antibody targeting CD20. The first Phase I dose escalation study for ATTCK20 is taking place in Singapore at National University Hospital (NUH) and Singapore General Hospital (SGH). T-cells from patients in the study are processed at the Tissue Engineering & Cell Therapy (TECT) Laboratory at NUH. The Hematology-Oncology Research Group Trial Unit within the National University Cancer Institute, Singapore (View Source) manages and supports all aspects of the clinical trial. At present, the unit is conducting over 60 clinical trials, many of which are Phase I and II studies. The Hematopoietic Progenitor Cell Transplant Program is the only one in Asia accredited by the Foundation for the Accreditation of Cellular Therapy (FACT).

"This study is designed to translate recent laboratory findings into clinical application," said Unum’s Scientific Founder Dario Campana, MD, PhD. "The efficacy of ACTR T-cells shown in our preclinical studies, together with the demonstrated feasibility of infusing autologous T-cells, forms a compelling rationale for the clinical testing of this novel approach. We look forward to enrolling patients in the ATTCK20 study and will continue to plan for additional clinical studies to leverage our ACTR technology with tumor-targeting antibodies in other types of cancer."

ACTR AND ATTCK20

ACTR is a chimeric protein that combines components from receptors normally found on two different human immune cell types – natural killer (NK) cells and T-cells – to create a novel cancer cell killing activity. As reported earlier this year in the journal Cancer Research[1], T-cells bearing the ACTR receptor can be armed to attack a tumor by combining with a monoclonal antibody that binds antigens on the cancer cell surface. CD20 is expressed on cancer cells from many patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Rituximab, an antibody specific for CD20, is currently part of standard therapy for these indications. Studies carried out in Dr. Campana’s laboratory show remarkable enhancement in the activity of rituximab when it is armed with ACTR T-cells.

Unum has built a platform for cancer treatment based upon ACTR. In contrast to other approaches that are limited to a single target and treat a narrow set of tumors, Unum’s approach is not restricted by antigen and may have applications for treating many types of cancers. The ATTCK20 study will be the first clinical trial to assess clinical candidates engineered with the ACTR technology.

On December 1, 2014 Exelixis reported top-line results from the final analysis of COMET-2 (NCT01522443), a randomized, double-blind, controlled trial of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC) who are suffering from moderate to severe pain despite optimized narcotic medication, and whose disease has progressed following treatment with docetaxel as well as abiraterone and/or enzalutamide (Press release Exelixis, DEC 1, 2014, View Source;p=RssLanding&cat=news&id=1993605 [SID:1234501037]). The trial did not meet its primary endpoint of alleviation of bone pain, as determined by comparing the percentage of patients in the two treatment arms who achieved a pain response at Week 6 that was confirmed at Week 12 without increase in narcotic medication. Fifteen percent of patients in the cabozantinib arm reported a pain response, compared to 17 percent of patients in the control arm receiving mitoxantrone/ prednisone. The difference in pain response between the arms was not statistically significant. The safety profile of cabozantinib in the trial was consistent with that observed in previous studies in mCRPC.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Following the COMET-1 top-line results announced in September, we deprioritized the cabozantinib development program in mCRPC; at that time, we also initiated a significant workforce reduction in order to focus our development efforts and financial resources on the pivotal phase 3 studies of cabozantinib in metastatic renal cell carcinoma (RCC) and advanced hepatocellular carcinoma (HCC)," said Michael Morrissey, Ph.D., president and chief executive officer of Exelixis. "With target enrollment in the METEOR study in RCC recently achieved, we anticipate top-line results in the second quarter of 2015. We also look forward to Roche and Genentech’s continued regulatory progress with cobimetinib for metastatic melanoma. The EU review is underway and the U.S. filing is expected before year-end, which could ultimately lead to our opportunity to co-promote cobimetinib in the U.S. if it is approved for this indication."

Exelixis will submit the results from the COMET program for potential presentation at a future medical meeting.

On December 1, 2014 Celator Pharmaceuticals reported that the independent Data and Safety Monitoring Board (DSMB) for the Company’s Phase 3 clinical study of CPX-351 (cytarabine:daunorubicin) Liposome for Injection versus the conventional cytarabine and daunorubicin treatment regimen (commonly referred to as 7+3) as first-line therapy in older patients with high-risk (secondary) acute myeloid leukemia (AML), has completed a planned safety review and recommended that the study continue as planned without any modifications (Press release Celator Pharmaceuticals, DEC 1, 2014, View Source [SID:1234501036]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased with the DSMB recommendation to continue with the pivotal Phase 3 study of CPX-351 following this safety analysis of the first 225 randomized patients, out of a total of 309 patients who were enrolled in the study," said Arthur Louie, Chief Medical Officer of Celator Pharmaceuticals. "With the Phase 3 study having recently completed enrollment ahead of schedule, we look forward to the induction response rate analysis, which we expect in the second quarter of 2015."

The DSMB assessment was based on a pre-planned safety analysis on the first 225 randomized patients included in the study with a minimum of 60 days of follow-up. The DSMB will conduct an additional review after all patients become evaluable for safety review.

The Phase 3 study is being conducted in partnership with The Leukemia & Lymphoma Society (LLS) through its Therapy Acceleration Program (TAP), which has supported the development of CPX-351 beginning in Phase 2.

"We are excited with the progress of the Phase 3 study," said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals. "In addition to the induction response rate data, a secondary endpoint, from the study in the second quarter of next year, we expect the overall survival data, the primary endpoint, in the first quarter of 2016. We also continue to work with investigators to study CPX-351 in other AML patient populations, as well as in other hematologic malignancies, with the hope of providing improved clinical benefits to these patients."

The study (Protocol NCT01696084) enrolled patients between the ages of 60 and 75 who have pathological diagnosis of AML according to WHO criteria with confirmation of:

Therapy-related AML,
AML with a history of myelodysplasia (MDS),
AML with a history of chronic myelomonocytic leukemia (CMMoL), or
De novo AML with karyotypic abnormalities characteristic of MDS.

Patients were randomized 1:1 to receive either CPX-351 (100u/m2; days 1, 3, and 5 by 90 minute infusion) or 7+3 (cytarabine 100mg/m2/day by continuous infusion for 7 days and daunorubicin 60mg/m2 on days 1, 2, and 3). Patients are monitored for all clinical adverse events as well as laboratory evaluations. The primary efficacy endpoint of the study is overall survival. The study is being conducted in the United States and Canada, with more than 40 leading cancer centers participating.

On December 1, 2014 Pharmacyclics reported the acceptance of a Type II variation application for IMBRUVICA (ibrutinib) by the European Medicines Agency (EMA) (Press release Pharmacyclics, DEC 1, 2014, View Source [SID:1234501035]). This submission, filed by strategic partner Janssen-Cilag International NV (Janssen), represents a potential label expansion for IMBRUVICA in the European Union (EU) for the treatment of adult patients with Waldenstrom’s macroglobulinemia (WM), a rare type of B-cell lymphoma for which treatment options are limited in the EU. If approved, IMBRUVICA would be the first label specifically authorized to treat WM.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

IMBRUVICA is a first-in-class, oral, once-daily, therapy being jointly developed and commercialized in the United States (U.S.) by Pharmacyclics and Janssen Biotech, Inc. Janssen affiliates will hold the marketing authorization and market IMBRUVICA in EMEA (Europe, Middle East, Africa), as well as the rest of the world, outside the U.S.

"This additional application in the EU shows the priority and urgency with which we, and our collaboration partner Janssen, pursue the ongoing potential for IMBRUVICA," said Thorsten Graef, M.D., Ph.D., Vice President of Clinical Science, Pharmacyclics. "If approved, IMBRUVICA could address a very important unmet need for patients with WM in Europe, who currently have limited treatment options."

The acceptance of the WM Type II variation submission for IMBRUVICA triggers a $20 million milestone payment to Pharmacyclics under its collaboration agreement with Janssen Biotech, Inc.

The EMA WM filing follows the supplemental New Drug Application submission for IMBRUVICA to the U.S. Food and Drug Administration (FDA), which was submitted by Pharmacyclics in October 2014, for its use in the treatment of patients with WM. Both the FDA and EMA filings were based on data from a Phase II study evaluating the use of IMBRUVICA in WM patients, which was led by Dr. Steven Treon from the Dana-Farber Cancer Institute.

WM is a slow-growing, currently incurable, rare type of B-cell lymphoma for which there are no EU-wide approved drugs. The median age at diagnosis is 63-68 years of age and incidence rates among men and women in the EU are approximately 7.3 and 4.2 per million persons, respectively. WM begins with a malignant change to the B cell, a type of white blood cell (lymphocyte), during its maturation so that it continues to reproduce more malignant B cells.