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Five Prime Therapeutics Completes Phase 1 Safety Lead-In and Initiates Phase 3, Global Registrational Trial of Bemarituzumab in Front-Line Advanced Gastric and Gastroesophageal Junction Cancers

On September 10, 2018 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a biotechnology company discovering and developing innovative immuno-oncology protein therapeutics, reported that the company completed the Phase 1 safety lead-in portion and has initiated the Phase 3 portion of the FIGHT Phase 1/3 clinical trial of bemarituzumab (FPA144), an isoform-selective anti-FGF receptor 2b antibody, in combination with chemotherapy in patients with previously untreated, advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer (Press release, Five Prime Therapeutics, SEPT 10, 2018, View Source [SID1234529372]).

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"We are very pleased to have completed the safety lead-in and move into the Phase 3 registrational portion of the bemarituzumab trial in patients with gastric cancer," said Helen Collins, M.D., Senior Vice President and Chief Medical Officer of Five Prime. "Patients with advanced gastric cancer are in dire need of new treatment options. Bemarituzumab is a targeted therapy and we are using state-of-the-art diagnostic tools to help us identify patients with FGFR2b overexpression, which is associated with a worse prognosis. Bemarituzumab has demonstrated encouraging monotherapy activity as a late-line treatment for gastric cancer and we believe that combining with chemotherapy in the front-line setting should provide the greatest patient benefit."

In December 2017, Five Prime initiated the Phase 1 portion (NCT03343301) of the Phase 1/3 FIGHT (FGFR2b Inhibition in Gastric and Gastroesophageal Junction Cancer Treatment) global registrational trial. The Phase 1 portion tested bemarituzumab doses of 6 mg/kg and 15 mg/kg in combination with modified FOLFOX6 (mFOLFOX6) with no overlapping toxicities identified.

The randomized, controlled, double-blinded Phase 3 portion of the FIGHT trial will evaluate bemarituzumab plus mFOLFOX6 versus placebo plus mFOLFOX6 in approximately 550 patients with gastric cancer (GC) or gastroesophageal junction (GEJ) cancer whose tumors overexpress FGFR2b. The Phase 3 trial will include approximately 250 sites in the U.S., Europe and Asia, including China, South Korea and Japan, where the incidence of gastric cancer is high. Zai Lab will manage the Phase 3 portion of the FIGHT trial in China.

The primary endpoint of the FIGHT trial is overall survival (OS) with secondary endpoints of progression-free survival (PFS), objective response rate (ORR), safety and pharmacokinetic (PK) parameters.

Unmet Need in GC and GEJ

GC, including GEJ cancer, is the fifth most common cancer worldwide and third leading cause of cancer death.

Current first-line chemotherapy treatment delays progression by approximately 6 months compared to best supportive care, but median OS remains poor with literature-reported ranges of approximately 10 to 11 months and PFS of approximately 6 months. The presence of FGFR2b overexpression is present in approximately 10% of patients with GC/GEJ and is associated with a worse prognosis. Few treatment options following progression are available after first-line chemotherapy and a significant unmet need remains in the treatment of GC/GEJ.

Five Prime is developing companion diagnostics to identify FGFR2b overexpression using an IHC test and FGFR2 gene amplification using ctDNA analysis. Five Prime will use both assays to select patients for the FIGHT trial.

About Bemarituzumab

Bemarituzumab is a first-in-class, isoform-selective, humanized monoclonal antibody in clinical development as a targeted immunotherapy for tumors that overexpress FGFR2b, a splice variant of a receptor for some members of the fibroblast growth factor (FGF) family. Bemarituzumab blocks FGFs 7, 10 and 22 from binding to FGFR2b, and has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) to increase direct tumor cell killing by recruiting natural killer (NK) cells. Clinical results to date suggest that the specificity of bemarituzumab avoids the dose-limiting toxicities that have been seen with less selective pan-FGFR tyrosine kinase inhibitors that act on multiple FGFRs, including FGFR2.

In December 2017, Five Prime and Zai Lab announced a strategic collaboration for the development and commercialization of bemarituzumab in Greater China.

Selecta Biosciences to Present at the Janney Healthcare Conference on September 17, 2018

On September 10, 2018 Selecta Biosciences, Inc. (Nasdaq: SELB), a clinical-stage biopharmaceutical company focused on unlocking the full potential of biologic therapies by mitigating unwanted immune responses, reported that CFO and Head of Corporate Strategy John Leaman, M.D., will present at the Janney Healthcare Conference in New York City at 9:05 a.m. ET on Monday, September 17, 2018 (Press release, Selecta Biosciences, SEPT 10, 2018, View Source [SID1234529371]). A live webcast of the presentation can be accessed via the Investors & Media section of the company’s website, View Source

Alkermes Initiates Clinical Evaluation of Novel Immuno-Oncology Drug Candidate ALKS 4230 in Combination With PD-1 Inhibitor Pembrolizumab

On September 10, 2018 Alkermes plc (Nasdaq : ALKS ) reported that it has expanded its ongoing phase 1 study for ALKS 4230, the company’s immuno-oncology drug candidate, to evaluate its safety and anti-tumor activity when administered in combination with the FDA-approved PD-1 inhibitor KEYTRUDA (pembrolizumab) in patients with advanced solid tumors (Press release, Alkermes, SEPT 10, 2018, View Source [SID1234529370]). ALKS 4230 is an engineered fusion protein designed to preferentially bind and signal through the intermediate affinity interleukin-2 (IL-2) receptor complex, thereby selectively activating and increasing the number of immunostimulatory tumor-killing immune cells while avoiding the expansion of immunosuppressive cells that interfere with anti-tumor response. Pembrolizumab is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.

"The emergence of therapeutics targeting the PD-1 pathway has revolutionized the field of oncology, yet there remains significant opportunity to improve the clinical benefit of checkpoint inhibitors for the treatment of solid tumors. There is strong scientific rationale supporting the combination of PD-1 pathway inhibition with cytokine therapy such as ALKS 4230 to activate the body’s own immune system to fight cancer, and the potential synergies of ALKS 4230 and pembrolizumab on anti-tumor activity may expand treatment options for patients in a variety of tumor settings," said Craig Hopkinson, M.D., Chief Medical Officer and Senior Vice President of Medicines Development and Medical Affairs at Alkermes. "We’ve accelerated clinical evaluation of ALKS 4230 in combination with pembrolizumab based on data from our ongoing monotherapy dose-escalation stage of the phase 1 study, where ALKS 4230 demonstrated dose-dependent pharmacodynamic effects on circulating natural killer cells and CD8+ T cells, and minimal and non-dose dependent effects on immunosuppressive regulatory T cells. These data validate our design rationale for ALKS 4230, and we look forward to sharing initial data from our dose-escalation cohorts at a medical meeting later this year."

Evaluation of the safety and anti-tumor activity of ALKS 4230 in combination with pembrolizumab will be assessed in certain PD-1 approved tumor types in both refractory and treatment naïve patients, including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, gastric cancer, urothelial carcinoma and microsatellite instability-high cancers. Melanoma and renal cell carcinoma will also be evaluated in the cohort of treatment naïve patients. The combination of ALKS 4230 and pembrolizumab will also be assessed in certain PD-1 unapproved tumor types, including colorectal cancer, triple-negative breast cancer, ovarian carcinoma, soft tissue sarcomas, and patients with metastatic NSCLC whose tumors express low or undetectable PD-L1 (tumor proportion score <1%).

About the Phase 1 Study

The Alkermes-sponsored phase 1 study for ALKS 4230 includes three distinct stages: the ongoing monotherapy dose-escalation stage, the planned monotherapy dose-expansion stage and the newly initiated combination therapy stage with pembrolizumab. The dose-escalation stage is designed to determine a maximum tolerated dose of ALKS 4230 in a monotherapy setting and to identify the optimal dose range of ALKS 4230 based on measures of immunological-pharmacodynamic effects. Upon completion of the dose-escalation stage, the company expects to initiate the monotherapy dose-expansion stage in up to 42 patients with renal cell carcinoma or melanoma. The newly initiated combination therapy stage of the phase 1 study will assess the safety profile and anti-tumor activity of ALKS 4230 with pembrolizumab in up to 148 patients with select advanced solid tumors. This combination therapy stage will be run independent of, and concurrently with, the monotherapy dose-escalation and dose-expansion stages of the trial.

Anti-tumor response and duration of response assessments in the dose-expansion and combination stages of the phase 1 study will be based on investigator-assessed, immune-related response (irRC) criteria and independent, central, blinded radiographic review per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.

About ALKS 4230

ALKS 4230 is an engineered fusion protein designed to preferentially bind and signal through the intermediate affinity interleukin-2 (IL-2) receptor complex, thereby selectively activating and increasing the number of immunostimulatory tumor-killing immune cells while avoiding the expansion of immunosuppressive cells that interfere with anti-tumor response. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects while overcoming limitations of existing IL-2 therapy, which activates both immunosuppressive and tumor-killing immune cells.

CCAB And Triumvira Immunologics Announce Triumvira’s License Agreement with University of Toronto for the Discovery of Antibody Drug Development Candidates

On September 10, 2018 The Centre for the Commercialization of Antibodies and Biologics (CCAB) and Triumvira Immunologics, Inc. (Triumvira), reported a new licensing agreement between the University of Toronto (U of T) and Triumvira (Press release, Triumvira Immunologics, SEP 10, 2018, View Source [SID1234529369]). The agreement provides Triumvira with an exclusive license for antibodies discovered at the U of T on specified therapeutic targets. Triumvira is a privately held biopharmaceutical company with R&D facilities in Hamilton, ON, that is developing a novel platform for engineering T cells to attack multiple cancer types.

CCAB is the assigned agent for the U of T for the commercialization of a large portfolio of human antibodies. Under the terms of the agreement, U of T will receive up-front fees, milestone payments and royalty payments on net sales of products on three therapeutic targets: BCMA, ROR1 and one undisclosed target.

"We are very pleased to be working with The Centre for the Commercialization of Antibodies and Biologics and the University of Toronto under this new licencing agreement," said Paul Lammers, MD, MSc, President and Chief Executive Officer of Triumvira. "This partnership is critical as we work to bring new treatments to patients in need through our proprietary T Cell-Antigen Coupler (TAC) technology."

Triumvira’s lead therapeutic candidate, TAC01-CD19, is a CD19-directed T cell product for the treatment of B cell malignancies and is anticipated to enter Phase I clinical trials in H1 2019 in patients with diffuse large B cell lymphoma (DLBCL). The company is also developing a series of products for solid tumors.

"Collaboration is a vital part in the development of new therapeutics. These types of agreements continue to strengthen the connection between academia and industry and help to translate the wealth of scientific knowledge from the laboratories at our world-class universities to the clinic," CCAB Chief Executive Officer Robert Verhagen said.

Xspray Pharma announces positive clinical data for its lead product candidate HyNap-Dasa

On September 9, 2018. Xspray Pharma reported positive data from a clinical bioequivalence study with the company’s lead product candidate HyNap-Dasa (Press release, Xspray, SEP 9, 2018, View Source [SID1234649534]). The study results confirmed its primary aim to show bioequivalence of an optimized formulation of HyNap-Dasa compared to Sprycel. The data will be instrumental in the design of the planned registration study for an ANDA application.
The completed clinical Phase I study examined HyNap-Dasa’s bioavailability compared to the dasatinib cancer drug, currently marketed as Sprycel for the treatment of chronic myeloid leukemia (CML). In the study, bioavailability of two different tablet formulations of HyNap-Dasa was tested in comparison with Sprycel tablets in 16 healthy subjects. The results are very positive and confirm the validity of Xspray’s patented formulation technology. The planned studies required to take HyNap-Dasa to final registration studies will now be performed as planned. The results also strengthen the potential for additional product candidates in the pipeline being developed with the same technology to reach the market.

"I am happy to see that the data so strongly confirm our technology. The outcome of this study represents an important milestone for Xspray Pharma as it means that we now can initiate the preparation of the pivotal phase of the clinical program, taking us closer to a commercial launch of HyNap-Dasa. Furthermore, the results pave the way also for additional product candidates in our pipeline. It signifies a new and important step in our development as a company" said Per Andersson, CEO of Xspray Pharma.

The clinical results in summary:

The study compared the pharmacokinetic parameters Cmax and AUC for the originator product Sprycel and two different HyNap tablet formulations of dasatinib. Sixteen healthy volunteers received single doses of each product in a cross-over design. Although this study was not powered to demonstrate formal bioequivalence, an analysis of preliminary data indicate that bioequivalence with Sprycel was achieved for one of the HyNap formulations. The results demonstrate a high likelihood that formal bioequivalence will be achieved in an adequately powered study.

Sprycel is a registered trademark of Bristol-Myers Squibb.