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Phase III data shows Sandoz’ proposed biosimilar pegfilgrastim has similar safety and efficacy as the reference product

On December 2015 Sandoz, a Novartis company and global leader in biosimilars, reported results from the PROTECT 2 study which compared the safety and efficacy of proposed biosimilar pegfilgrastim with the reference product, Neulasta* (Press release, Novartis, DEC 7, 2015, View Source [SID:1234508469]). The study met its primary endpoints – showing it to be both equivalent and non-inferior to the reference product. Data was presented at the American Society of Hematology (ASH) (Free ASH Whitepaper), Orlando, Florida.

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Additional data from the study showed that there were no clinically meaningful differences between the proposed biosimilar pegfilgrastim and the reference product. Adverse events were similar and consistent with the known safety profile of pegfilgrastim, and no neutralizing anti-pegfilgrastim antibodies were detected.

"The positive data from the PROTECT 2 study is promising in that it will add to the body of evidence being developed on biosimilars. These findings could lead to another high-quality supportive care treatment option for physicians and oncology patients" said Kimberly Blackwell, MD, Professor of Medicine, Assistant Professor of Radiation Oncology, Duke University School of Medicine and primary investigator for the study.

Malte Peters, Head Biopharmaceutical Clinical Development, Sandoz said "The PROTECT 2 data is yet another demonstration of the substantial progress we are making with our biosimilar programs and the commitment we have made to improve patient access to these important medicines."

Sandoz has an unwavering commitment to increasing patient access to high-quality biosimilars. It is the pioneer and global market leader in biosimilars and was the first to launch biosimilars in the United States, Europe and Japan. Sandoz has a leading biosimilar pipeline with programs in various stages of development – the company plans to make 10 regulatory filings over a three year period (2015-2017) having already announced two. On November 18, 2015, Sandoz announced that the FDA accepted its regulatory filing for the proposed biosimilar pegfilgrastim. As part of the Novartis Group, Sandoz is well-positioned to lead the biosimilars industry based on its deep experience and capabilities in development, manufacturing and commercialization.

About PROTECT 2
The PROTECT 2 study was a global, randomized, double-blind trial involving 308 patients carried out in the United States, Latin America, Asia and Europe. The safety and immunogenicity of the proposed biosimilar was assessed for four weeks after the final study drug administration. The study analyzed the duration of severe neutropenia (DSN), which was also the primary endpoint.

About PROTECT 1
PROTECT 1 was a randomized, double-blind trial comparing the efficacy and safety of the proposed biosimilar pegfilgrastim (LA-EP2006) with reference pegfilgrastim in patients with breast cancer. PROTECT 1 data will be presented at San Antonio Breast Cancer Symposium, December 9, 2015 at 5 PM CST (SABCS Abstract #P1-10-01).

Kite Pharma Presents Phase 1 Results From ZUMA-1 at the 57th American Society of Hematology (ASH) Annual Meeting

On December 7, 2015 Kite Pharma, Inc. (Nasdaq:KITE) reported clinical results and biomarker data for the phase 1 portion of Kite’s ZUMA-1 trial of KTE-C19 in patients with refractory, aggressive non-Hodgkin lymphoma (NHL) (Press release, Kite Pharma, DEC 7, 2015, View Source [SID:1234508467]). KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a chimeric antigen receptor (CAR) designed to target the antigen CD19, a protein expressed on the cell surface of B cell lymphomas and leukemias.

David Chang, M.D., Ph.D., Kite Pharma’s Executive Vice President, Research and Development, and Chief Medical Officer, commented, "We are encouraged by these early clinical findings from our first company-sponsored, multi-center clinical trial in this highly refractory patient population. The overall safety, efficacy, and biomarker data were generally consistent with previously published data from the National Cancer Institute (NCI) and supported advancing ZUMA-1 to the pivotal phase. We look forward to providing interim data from the pivotal phase 2 portion of the study in 2016."

A summary of the ZUMA-1 Poster Presentations at ASH (Free ASH Whitepaper):

"Phase 1 Clinical Results of the ZUMA-1 (KTE-C19-101) Study: A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of Anti-CD19 CAR T Cells (KTE-C19) in Subjects with Refractory Aggressive Non-Hodgkin Lymphoma (NHL)." Abstract #3991; Presenter: Frederick Locke M.D., Moffitt Cancer Center; Monday, December 7, 2015: 6:00-8:00pm Eastern.

Phase 1 of the ZUMA-1 study treated a total of 7 patients with refractory, aggressive diffuse large B cell lymphoma (DLBCL)
KTE-C19 was administered at a target dose of 2 x 106 (minimum 1 x 106) anti-CD19 CAR T cells/kg body weight after a fixed-dose conditioning chemotherapy regimen

KTE-C19 was successfully manufactured for all leukapheresed subjects

KTE-C19 related adverse events consisted predominantly of cytokine release syndrome (CRS) and neurotoxicity, which were self-limited and generally reversible

One subject experienced dose-limiting toxicities of grade 4 encephalopathy and CRS, and grade 5 intracranial hemorrhage. The grade 5 event was deemed unrelated to KTE-C19 per the study investigator

Four complete remissions (CRs) and one partial remission (PR) were observed, representing an overall objective response rate of 71% (5/7)

All CRs were observed at one month

Three subjects had ongoing CRs at three months.

"Phase 1 Biomarker Analysis of the ZUMA-1 (KTE-C19-101) Study: A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of Anti-CD19 CAR T Cells (KTE-C19) in Subjects with Refractory Aggressive Non-Hodgkin Lymphoma (NHL)." Abstract number #2730; Presenter: Sattva S. Neelapu, M.D., The University of Texas MD Anderson Cancer Center; Sunday, December 6, 2015: 6:00-8:00pm Eastern.

In vitro and in vivo characteristics of KTE-C19 from 7 subjects in the Phase 1 portion of ZUMA-1 study were evaluated by flow cytometry, co-culture, and a panel of cytokines, chemokines and immune effector related markers

KTE-C19 contains naïve and central memory T cells. CAR T cells peaked within 2 weeks post infusion and were detectable at 1-3+ months post-infusion

Select homeostatic, pro-inflammatory/regulatory cytokines, tumor homing chemokines and effector molecules peaked within 1-2 weeks post-infusion and generally decreased within 3 weeks

The overall product characteristics and pharmacodynamic profile of KTE-C19 in ZUMA-1 phase 1 subjects were consistent with what has been observed with anti-CD19 CAR T cell therapy in the ongoing NCI study.

Kite Pharma Announces Clinical Biomarker Results of Anti-CD19 CAR T Cell Therapy at the 57th American Society of Hematology Annual Meeting (ASH)

On December 7, 2015 Kite Pharma, Inc. (Nasdaq:KITE) reported clinical biomarker data and product characteristics for anti-CD19 chimeric antigen receptor (CAR) T cell therapy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) enrolled in an ongoing phase 1-2 clinical trial at the National Cancer Institute (NCI), which is being conducted under a Cooperative Research and Development Agreement (CRADA) between Kite and the NCI (Press release, Kite Pharma, DEC 7, 2015, View Source [SID:1234508466]). In this clinical trial, patients with a range of B cell cancers were conditioned with cyclophosphamide and fludarabine prior to receiving anti-CD19 CAR T cell therapy.

Two posters were presented at the ASH (Free ASH Whitepaper) meeting from the NCI trial:

"Pharmacodynamic Profile and Clinical Response in Patients with B-Cell Malignancies of Anti-CD19 CAR T-Cell Therapy." Abstract #2042; Presenter: Dr. Adrian Bot, Kite Pharma; Saturday, December 5, 2015: 5:30 – 7:30 PM Eastern.

This study analyzed the product characteristics and biological activity of the anti-CD19 CAR T cells and concluded that anti-CD19 CAR T cells are polyfunctional, capable of producing a broad range of immune modulating cytokines, chemokines and effector molecules that peak sequentially.

This analysis included 17 patients treated with a low dose conditioning chemotherapy regimen (cyclophosphamide 300-500 mg/m2/day and fludarabine 30 mg/m2/day for 3 days) of which 10 received anti-CD19 CAR T cells that were manufactured under a new process, which was co-developed with Kite. The objective response rate was 71% (35% complete remission (CR)) overall and 70% (40% CR) among those treated with cells manufactured using the new process. Grade 3 or 4 cytokine release syndrome or neurotoxicity was observed in 59% of patients and was generally reversible.

"Cyclophosphamide and Fludarabine Conditioning Chemotherapy Induces a Key Homeostatic Cytokine Profile in Patients Prior to CAR T Cell Therapy." Abstract #4426; Presenter: Dr. Adrian Bot, Kite Pharma; Monday, December 7, 2015: 6:00 – 8:00 PM Eastern.

The clinical researchers found that the conditioning regimen of cyclophosphamide and fludarabine triggered changes in several key cytokines and chemokines that could drive expansion, activation, and trafficking of CAR T cells. Preliminary results suggest that the magnitudes of rise in interleukin-15 and reduction in perforin are associated with objective responses.

David Chang, M.D., Ph.D., Kite’s Executive Vice President, Research and Development, and Chief Medical Officer, commented, "The results being reported at ASH (Free ASH Whitepaper) provide meaningful insight into the importance of an optimized conditioning chemotherapy regimen, as well as the impact of the manufacturing approach on the effect of CAR T cell therapy. These findings have guided the design of Kite’s ongoing program for KTE-C19 (anti-CD19 CAR T cell therapy), which is currently enrolling patients in multiple clinical trials to support product registration."

Threshold Pharmaceuticals Announces Its Two Phase 3 Studies Evaluating Evofosfamide Did Not Meet Primary Endpoints

On December 7, 2015 Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) reported the outcomes of two Phase 3 cancer studies (MAESTRO and TH-CR-406/SARC021) of evofosfamide (previously known as TH-302), an investigational hypoxia-activated prodrug, which is being evaluated for first-line treatment of advanced pancreatic adenocarcinoma and advanced soft tissue sarcoma, in combination with chemotherapy (Press release, Threshold Pharmaceuticals, DEC 7, 2015, View Source [SID:1234508463]). The Phase 3 studies are being conducted under Threshold’s collaboration with Merck KGaA, Darmstadt, Germany.

In the Phase 3 MAESTRO study, patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma treated with evofosfamide in combination with gemcitabine did not demonstrate a statistically significant improvement in overall survival (OS) compared with gemcitabine plus placebo (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.71 – 1.01; p=0.0589).

In the Phase 3 TH-CR-406/SARC021 study being conducted in collaboration with the Sarcoma Alliance for Research through Collaboration (SARC), patients with locally advanced unresectable or metastatic soft tissue sarcoma treated with evofosfamide in combination with doxorubicin did not demonstrate a statistically significant improvement in OS compared with doxorubicin alone (HR: 1.06; 95% CI: 0.88 – 1.29).

Patient safety was monitored in MAESTRO and TH-CR-406/SARC021 by independent data monitoring committees throughout the conduct of each study. No new clinically significant safety findings were observed.

Detailed results from both studies will be submitted for presentation at upcoming international scientific meetings and for publication in peer-reviewed journals. Threshold will not be pursing further development of evofosfamide in soft tissue sarcoma and pancreatic cancer.

"We are surprised and disappointed that these studies did not show that evofosfamide could extend the lives of patients with these two difficult-to-treat diseases," said Barry Selick, Ph.D., Chief Executive Officer at Threshold. "Threshold has been pursuing evofosfamide for over ten years in collaboration with world-class scientists and investigators throughout the world. While we believe there remains substantial data to support the role of hypoxia in cancer treatment resistance, we are deeply frustrated with our inability in these trials to impact that in a meaningful way. I would like to thank all of the patients and their families, and the physicians, nurses, and support staff who participated in these studies."

Conference Call and Webcast
At 8:30 a.m. Eastern Time on Monday December 7, 2015, Threshold’s management will host a conference call and a simultaneous webcast. The webcast can be accessed on the company’s website in the Investors/Webcasts section View Source Alternatively, please call 1- (888) 767-9745 (U.S) or (440) 996-5547 (international). The conference ID number is 99761325. The webcast will be archived on Threshold’s website for at least 30 days.

About TH-CR-406/SARC021
TH-CR-406/SARC021 is a randomized, open-label, global, multicenter Phase 3 study, that was designed to assess the efficacy and safety of evofosfamide (300 mg/m2) in combination with doxorubicin (75 mg/m2) compared with doxorubicin alone, in patients with locally advanced unresectable or metastatic soft tissue sarcoma previously untreated with chemotherapy. A total of 640 patients were randomized in the study. The primary endpoint of the study is OS. Secondary endpoints include progression-free survival (PFS), response rate, safety and pharmacokinetics.

About MAESTRO
MAESTRO (MetAstatic or unrESectable pancreaTic adenocaRcinOma) is a randomized, placebo-controlled, international, multicenter, double-blind Phase 3 study, that was designed to assess the efficacy and safety of evofosfamide (340 mg/m2) in combination with gemcitabine (1000 mg/m2), compared with gemcitabine and placebo, in patients with previously untreated, locally advanced, unresectable or metastatic pancreatic adenocarcinoma. A total of 693 patients were randomized in the study. The primary endpoint of the study is OS. Secondary endpoints include PFS, overall response rate, disease control rate, quality of life based on patient-reported outcomes, safety and tolerability, pharmacokinetics and biomarkers.

About Evofosfamide
Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic.

Evofosfamide is being studied in patients with locally advanced unresectable or metastatic soft tissue sarcoma and in patients with locally advanced unresectable or metastatic pancreatic cancer. Evofosfamide is also being investigated in a Phase 2 study designed to support registration for the treatment of non-squamous non-small cell lung cancer, and in earlier-stage clinical studies of other solid tumors and hematological malignancies.

Threshold has a global license and co-development agreement for evofosfamide with Merck KGaA, Darmstadt, Germany.

6-K – Report of foreign issuer [Rules 13a-16 and 15d-16]

On December 7, 2015 Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs being developed to treat inflammatory diseases, cancer and sexual dysfunction, reported that its subsidiary, OphthaliX (OTCQB:OPLI), has completed patient enrollment for its Phase II trial of CF101 in the treatment of glaucoma (Filing, 6-K, Can-Fite BioPharma, DEC 7, 2015, View Source [SID:1234508459]).

GlobalData estimates that the treatment market for glaucoma in the seven major markets was $2.4 billion in 2013 and will grow to approximately $3 billion by 2023. Most glaucoma drugs on the market today are generic eye drops. The key advantages of CF101 are its oral administration and excellent safety profile.

The Phase II trial is being conducted in Europe and Israel and full enrollment of 88 patients has been achieved. Top line results are expected in mid-2016. The study is being conducted with two cohorts. In the first cohort patients were treated with 1 mg CF101 and placebo. Blinded results from this cohort showed that the drug had a favorable safety profile and was well tolerated. In the second cohort, dosage was increased, with patients receiving 2 mg of CF101 and matching placebo, given orally every 12 hours for 16 weeks. The drug’s mechanism of action has been validated in an article by a leading researcher from University College London in the UK, Dr. Cordiero, who showed that the A3 adenosine receptor (A3AR) agonist has a neuroprotective effect in the eye via inhibition of retinal ganglion cell apoptosis resulting in a significant decrease in intraocular pressure (IOP).

"Glaucoma is a substantial global market in which CF101 is one of only a few oral drugs in development. Oral drugs like CF101 have the potential to increase patient compliance and be more convenient for the patient," stated Can-Fite CEO Dr. Pnina Fishman. "In prior human clinical studies, we’ve seen that CF101 reduced IOP, the most important and only modifiable risk factor for glaucoma."

CF101 has an issued patent in the U.S. for the reduction of IOP, which expires in 2030. Several similar applications are pending in major global markets. OphthaliX has licensed the exclusive rights for the use and development of CF101 in the field of ophthalmic diseases from Can-Fite.

About CF101

CF101, an A3 adenosine receptor (A3AR) agonist, is a novel, first in class small molecule orally bioavailable drug which binds with high affinity and selectivity to the A3AR, which is known to be over-expressed in inflammatory cells. The drug acts as a neuro-protective agent and prevents apoptosis of retinal ganglion cells.