On September 26, 2016 ERYTECH Pharma (Paris:ERYP) (ADR:EYRYY) (Euronext Paris: ERYP), a French biopharmaceutical company developing ‘tumor starvation’ treatments for acute leukemia and other oncology indications with unmet medical needs, reported the final patient has been enrolled in its Phase 2 trial of eryaspase, also known as ERY-ASP or GRASPA, for the treatment of pancreatic cancer (Press release, ERYtech Pharma, SEP 26, 2016, View Source [SID:SID1234515415]).

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!

The multicenter, randomized Phase 2 trial is evaluating eryaspase as a second-line treatment of patients with metastatic pancreatic cancer. In the study conducted in France, eryaspase was added to the standard of care (currently Gemcitabine or FOLFOX regimen) and then compared to the standard of care alone in a 2-to-1 randomization. The primary endpoint of the trial is progression-free survival (PFS) at four months.

The trial has completed enrollment of 139 patients and we expect to report primary results from this trial by early 2017.

"The Phase 2 trial of eryaspase for pancreatic cancer is, to our knowledge, the largest cohort of solid tumor patients treated with an asparaginase-based product to date," said Gil Beyen, Chairman and CEO of ERYTECH. "Previously, deprivation of asparagine has shown to limit growth of pancreatic and other solid tumors in preclinical models, but clinical proof of concept has not yet been established. We believe a positive efficacy signal in this trial could open a potentially large application area for asparagine depletion in certain solid tumors."

About pancreatic cancer:

Pancreatic cancer is a disease in which malignant (cancer) cells are found in the tissues of the pancreas. Every year there are about 150,000 new cases of pancreatic cancer diagnosed in Europe and the United States. Pancreatic cancer is a particularly aggressive cancer, with a five-year survival rate of less than 10% and is currently the fourth most common cause of cancer death in the EU for men and women. Pancreatic cancer could be a suitable indication for eryaspase because it involves a large proportion of tumors that are believed to be sensitive to asparagine depletion, allowing it to potentially have an impact.

On September 26, 2016 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform, reported that it has today presented new preclinical data demonstrating in vivo efficacy of its lead 4-1BB (CD137)-based bispecific cancer immunotherapeutic drug candidate, PRS-343, at the 2016 CRI-CIMT-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) – Translating Science into Survival, taking place in New York City (Press release, Pieris, SEP 26, 2016, View Source [SID:SID1234515414]).

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!

The in vivo data show that treatment of HER2-positive tumor-bearing animals with PRS-343 provided dose-dependent, dual anti-tumor activity by increasing the frequency of tumor-infiltrating lymphocytes via bispecific targeting of 4-1BB and HER2, as well as mediating tumor growth inhibition by direct antagonism of HER2 on tumor cells. In contrast, an agonistic anti-4-1BB benchmark monoclonal antibody (mAb) displayed neither tumor growth inhibition nor enhanced lymphocyte infiltration into tumors compared to an isotype control mAb, but preferentially activated T cells systemically, resulting in significant toxicity. A copy of the poster can be viewed and downloaded by clicking View Source

Louis Matis, M.D., Pieris SVP and Chief Development Officer, commented, "These new data support a differentiated mode of action for PRS-343 and demonstrate the potential benefits of tumor microenvironment-localized costimulatory T cell activation for both reduced systemic toxicity and higher efficacy in comparison to conventional agonistic anti-4-1BB mAbs. We look forward to the initiation of our phase 1 clinical trial of PRS-343 for the treatment of cancer patients planned for the first half of 2017."

About PRS-343
PRS-343 is a bispecific monoclonal antibody/Anticalin fusion protein comprised of a HER2 tumor-targeting mAb genetically linked to a potent anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). 4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes (TILs), and is therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.

On September 26, 2016 Kite Pharma, Inc., (Nasdaq:KITE) reported positive topline results from a pre-planned interim analysis of ZUMA-1 for its lead product candidate, KTE-C19, in patients with chemorefractory diffuse large B-cell lymphoma (DLBCL) (Press release, Kite Pharma, SEP 26, 2016, View Source [SID:SID1234515409]). KTE-C19 met the primary endpoint of objective response rate (ORR), p < 0.0001, with ORR of 76 percent, including 47 percent complete remissions (CR).

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!

ZUMA-1 enrolled patients with chemorefractory aggressive NHL into two cohorts. Cohort 1 included patients with DLBCL, and Cohort 2 enrolled patients with transformed follicular lymphoma (TFL) and primary mediastinal B-cell lymphoma (PMBCL). Kite’s intent is to seek regulatory approval of KTE-C19 in DLBCL, TFL and PMBCL based upon the combined data of both cohorts.

The interim analysis of ZUMA-1 evaluated the ORR in the first 51 patients in Cohort 1 with at least three months of follow-up. This analysis also included an additional 11 patients in Cohort 2. The table below summarizes the response rates from this interim analysis together with the previously reported results from the Phase 1 portion of ZUMA-1 (Neelapu ASCO (Free ASCO Whitepaper) 2016).

ZUMA-1 Phase 1 ZUMA-1 Phase 2
DLBCL (n=7)
DLBCL (n=51) TFL/PMBCL (n=11) Combined (n=62)

ORR
(%)
CR
(%)

ORR
(%)
CR
(%)
ORR
(%)
CR
(%)

ORR
(%)
CR
(%)
ORR 71 57 76 47 91 73 79 52
Month 3 43 43 39 33 64 64 44 39
Months 6 and 9 43 43 Data Pending

Across the combined 62 patients, the most common grade 3 or higher adverse events included neutropenia (66 percent), anemia (40 percent), febrile neutropenia (29 percent), thrombocytopenia (29 percent), and encephalopathy (26 percent). Grade 3 or higher cytokine release syndrome (CRS) and neurological toxicity was observed in 18 percent and 34 percent of patients, respectively. Two patients died from KTE-C19 related adverse events (hemophagocytic lymphohistiocytosis and cardiac arrest in the setting of CRS).

The Phase 2 interim outcomes in ZUMA-1 are largely consistent with results from the Phase 1 portion of the study and the National Cancer Institute (NCI) study based on the same CAR construct, a low-dose cyclophosphamide-fludaribine conditioning regimen, and Kite’s proprietary manufacturing process (Kochenderfer ASCO (Free ASCO Whitepaper) 2016).

"ZUMA-1 enrolled patients with chemorefractory aggressive NHL, a disease that is very difficult to treat. The combined CR rate of 39 percent at three months is very exciting as it represents nearly a five-fold increase from the CR rate of 8 percent seen in the SCHOLAR-1 study in a similar patient population," said Jeff Wiezorek, M.D., Senior Vice President of Clinical Development. "ZUMA-1 is the largest CAR-T study reported in NHL. We were able to manufacture KTE-C19 for 99 percent of patients enrolled in the study, and successfully handle the study logistics and adverse event management at over 20 sites, most of which had no prior experience in CAR-T therapy."

Additional data from this interim analysis will be submitted for presentation at an upcoming scientific meeting. The primary analysis of 101 patients with chemorefractory aggressive NHL (DLBCL, TFL and PMBCL) will include approximately six months of follow-up and is expected in the first quarter of 2017.

"We are grateful to the study participants and investigators who have made this important research possible. What started at the NCI over a decade ago with the pioneering work of Steven A. Rosenberg, M.D., Ph.D., has evolved into a technology that has the potential to fundamentally change the outlook of patients with cancer. For patients with aggressive NHL, every day matters and a new treatment option like KTE-C19 is desperately needed," said Arie Belldegrun, M.D., FACS, Chairman, President and Chief Executive Officer of Kite. "I am proud of what we have achieved to date and excited to apply our advanced learnings from ZUMA-1 to our ongoing clinical development programs to bring continued innovation to patients and the scientific community at large."

ZUMA-1 is supported in part by funding from The Leukemia & Lymphoma Society (LLS) Therapy Acceleration Program.

About KTE-C19

Kite Pharma’s lead product candidate, KTE-C19, is an investigational therapy in which a patient’s T-cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T-cells to kill cancer cells. KTE-C19 has been granted Breakthrough Therapy Designation status for DLBCL, TFL, and PMBCL by the U.S. Food and Drug Administration and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

On September 26, 2016 Mateon Therapeutics, Inc. (Nasdaq:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported a collaboration under which sites affiliated with US Oncology Research will participate in the FOCUS Study, Mateon’s recently initiated phase 2/3 clinical trial in platinum-resistant ovarian cancer (Press release, Mateon Therapeutics, SEP 26, 2016, View Source [SID:SID1234515403]).

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 to work with US Oncology Research, an outstanding organization that has had tremendous success in oncology-related clinical trials," stated William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "US Oncology Research is selective regarding the studies in which it participates. So we are pleased they recognize the importance of developing CA4P for women with platinum-resistant ovarian cancer."

US Oncology Research is a premier organization in the United States dedicated to bringing physicians, clinics and patients together for innovative cancer research in the community setting. One of the largest community-based oncology research programs in the U.S., US Oncology Research has nearly 150 affiliated locations as well as more than 900 affiliated investigators. The organization has played a role in the development of more than 60 FDA-approved cancer therapies, which represents about one-third of all cancer therapies approved by the FDA to date, and manages about 300 active clinical trials at any given time.

"Inhibition of tumor-related angiogenesis provides an important therapeutic option for women with recurrent ovarian cancer," stated Michael A. Bookman, M.D., Director, Gynecologic Oncology Research, US Oncology Research. "Strategies to combine Mateon’s CA4P, a novel vascular disrupting agent, with other agents, including bevacizumab, appear promising, and we are excited to offer our patients the opportunity to participate in this high-priority randomized trial."

About FOCUS
The FOCUS Study is a randomized, double-blind, 2-arm, parallel-group, phase 2/3 study to evaluate the efficacy and safety of physician’s choice chemotherapy (PCC) plus bevacizumab and CA4P versus PCC plus bevacizumab in patients with platinum-resistant ovarian cancer. The primary endpoint of the FOCUS Study is progression free survival (PFS). The Study will also evaluate CA4P’s effect on objective response rate (ORR), overall survival (OS) and other parameters. For additional information on the FOCUS Study, please visit www.clinicaltrials.gov, study identifier NCT02641639.