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Roche's Gazyvaro approved in Europe in combination with bendamustine for people with previously treated follicular lymphoma

On June 16, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Commission has approved Gazyvaro (obinutuzumab) in combination with bendamustine chemotherapy followed by Gazyvaro maintenance in people with follicular lymphoma who did not respond or who progressed during or up to six months after treatment with MabThera (rituximab) or a MabThera-containing regimen (Press release, Hoffmann-La Roche , JUN 15, 2016, View Source [SID:1234513393]).

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The approval is based on results from the pivotal phase III GADOLIN study which showed that Gazyva/Gazyvaro plus bendamustine, followed by Gazyva/Gazyvaro alone resulted in a 52 percent reduction (HR=0.48, 95 percent CI 0.34-0.68, p<0.0001) in the risk of disease worsening or death (progression-free survival, PFS), compared to bendamustine alone, as evaluated by an independent review committee (IRC). As assessed by investigator review, median PFS with the Gazyva/Gazyvaro regimen was more than double that with bendamustine alone (29.2 months vs. 13.7 months; HR=0.48, 95 percent CI 0.35-0.67, p<0.0001). People who received the Gazyva/Gazyvaro regimen also showed a 38 percent reduction (HR=0.62, 95 percent CI 0.39-0.98) in the risk of death (OS) compared to those who received bendamustine alone.

"Today’s approval is a significant milestone in the treatment of people with follicular lymphoma in Europe," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "For those who fail to achieve durable disease control with MabThera-based treatment, Gazyvaro plus bendamustine is an important new treatment option that has been shown to reduce the risk of disease progression or death by more than half."

Every day, more than 50 people in Europe are diagnosed with follicular lymphoma, the most common type of indolent (slow-growing) non-Hodgkin lymphoma (NHL).1,2 During initial therapy, response rates to MabThera-based treatment, the current standard of care, are greater than 90 percent, but there is no cure and people will eventually relapse.3,4 The disease becomes more difficult to treat at each relapse, and if a patient does not respond or relapses during or within 6 months of MabThera -containing treatment, they will likely need a different treatment. These people often have a poor prognosis and few treatment options.5

With this approval, Gazyvaro is now approved in Europe to treat two common types of blood cancer. Gazyvaro was previously approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia (CLL) and comorbidities that make them unsuitable for full-dose fludarabine based therapy. That approval was based on data from the pivotal CLL11 study, where the combination of Gazyva/Gazyvaro plus chlorambucil showed superior efficacy when compared head-to-head with MabThera/Rituxan plus chlorambucil and chlorambucil alone.

Gazyvaro is marketed as Gazyva outside of the EU and Switzerland. As announced in February this year, Gazyva received approval by the US Food and Drug Administration in combination with bendamustine followed by Gazyva alone as a treatment for people with follicular lymphoma who did not respond to a Rituxan-containing regimen, or whose follicular lymphoma returned after such treatment, based on the results of the GADOLIN study.

About the GADOLIN study
GADOLIN (NCT01059630; GA04753g) is a phase III open-label, multicentre, randomised two-arm study evaluating Gazyva/Gazyvaro plus bendamustine followed by Gazyva/Gazyvaro alone until disease progression or for up to two years compared to bendamustine alone. GADOLIN included 396 patients with indolent (slow-growing) non-Hodgkin lymphoma (NHL), including 321 patients with follicular lymphoma, whose disease progressed during or within six months of prior MabThera/Rituxan-based therapy. The primary endpoint of the study is progression-free survival (PFS) as assessed by an independent review committee (IRC), with secondary endpoints including PFS as assessed by investigator review, best overall response (BOR), complete response (CR), partial response (PR), duration of response, overall survival (OS) and safety profile. Results in follicular lymphoma showed:
The Gazyva/Gazyvaro regimen improved PFS compared to bendamustine alone, as assessed by IRC (HR=0.48, 95 percent CI 0.34-0.68, p<0.0001). Median PFS was not reached in those receiving the Gazyva/Gazyvaro regimen versus 13.8 months in those receiving bendamustine alone.

Investigator-assessed PFS was consistent with IRC-assessed PFS. As assessed by investigator review, median PFS with the Gazyva/Gazyvaro regimen was more than double that with bendamustine alone (29.2 months vs. 13.7 months; HR=0.48, 95 percent CI 0.35-0.67, p<0.0001).

The Gazyva/Gazyvaro regimen reduced the risk of death (OS) by 38 percent compared to bendamustine alone based on a post-hoc analysis eight months after the primary analysis (HR=0.62, 95 percent CI 0.39-0.98). The median OS has not yet been reached in either study arm.

The most common Grade 3-4 adverse events that occurred more often (at least 2 percent or greater) in those receiving the Gazyva/Gazyvaro regimen compared to those receiving bendamustine alone were low white blood cell count (33 percent vs. 26 percent), infusion-related reactions (11 percent vs. 6 percent) and urinary tract infection (3 percent vs. 0 percent), respectively.

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system. Gazyva/Gazyvaro is currently approved in more than 70 countries in combination with chlorambucil, for people with previously untreated chronic lymphocytic leukaemia. The approval was based on the CLL11 study, showing significant improvements with Gazyva/Gazyvaro plus chlorambucil across multiple clinical endpoints, including PFS, overall response rate (ORR), complete response rate (CR), and minimal residual disease (MRD) when compared head-to-head with MabThera/Rituxan plus chlorambucil and chlorambucil alone. Gazyva was also recently approved by the U.S. Food and Drug Administration in combination with bendamustine followed by Gazyva alone for people with follicular lymphoma who did not respond to a Rituxan-containing regimen, or whose follicular lymphoma returned after such treatment based on the results of the GADOLIN study. Gazyvaro is marketed as Gazyva outside of the EU and Switzerland.

As recently announced, the phase III GALLIUM study in people with previously untreated follicular lymphoma met its primary endpoint early. GALLIUM compared the efficacy and safety of Gazyva/Gazyvaro plus chemotherapy (CHOP, CVP or bendamustine) followed by Gazyva/Gazyvaro alone, head-to-head with MabThera/Rituxan plus chemotherapy followed by MabThera/Rituxan alone. Results from a pre-planned interim analysis showed that Gazyva/Gazyvaro-based treatment resulted in superior progression-free survival compared to MabThera/Rituxan-based treatment. Adverse events with either Gazyva/Gazyvaro or MabThera/Rituxan were consistent with what was seen in previous clinical trials when each was combined with various chemotherapies. Data from the GALLIUM study will be presented at an upcoming medical meeting and submitted to health authorities for approval consideration.
Gazyva/Gazyvaro is being studied in a large clinical programme, including the phase III GOYA study. GOYA is comparing Gazyva/Gazyvaro head-to-head with MabThera/Rituxan plus CHOP chemotherapy in first line diffuse large B-cell lymphoma (DLBCL). Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers.

About Follicular Lymphoma
Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL1. It is considered incurable and relapse is common. Every day, more than 50 people in Europe are diagnosed this type of NHL2. It is estimated that each year, more than 75,000 people are diagnosed with follicular lymphoma worldwide2.

Loxo Oncology Accepts Invitation to Present LOXO-101 to the FDA’s Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee

On June 15, 2016 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the company has accepted an invitation from the U.S. Food and Drug Administration (FDA) to participate in a meeting of the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee on June 29, 2016 (Press release, Loxo Oncology, JUN 15, 2016, View Source [SID:1234513370]). The purpose of the meeting is to improve and encourage the development of oncology and hematology drugs for pediatric use. These meetings are held regularly by the FDA, with various invited sponsors. At the meeting, Loxo Oncology plans to present an overview of LOXO-101, with an emphasis on opportunities for pediatric development.

Background material for this meeting will be available on the FDA website approximately 2 days prior to the meeting.

Clinical Development of LOXO-101 in Pediatric Cancers

Loxo Oncology is conducting an ongoing Phase 1 multicenter, open-label clinical trial in pediatric patients with advanced solid or primary CNS tumors. In order to meet the criteria for enrollment, patients must be between one year of age and 21 years of age with a locally advanced or metastatic solid tumor or primary CNS tumor that has progressed, or was nonresponsive to available therapies, and for which no standard or available curative therapy exists. Patients at least one month old are eligible for enrollment if they have a diagnosis of infantile/congenital fibrosarcoma or congenital mesoblastic nephroma, with a documented NTRK fusion that has progressed, or was nonresponsive to available therapies, and for whom no standard or available curative therapy exists. The primary endpoint of the trial is to explore the safety of LOXO-101. Secondary endpoints include the characterization of pharmacokinetic properties, the identification of the maximum tolerated dose and/or the Phase 2 dose, a description of antitumor activity and a description of pain and health related quality of life impact.

In April 2016, Loxo Oncology announced the publication of a case report in the online edition of Pediatric Blood and Cancer, co-authored with Nemours Children’s Hospital, Northwestern University and St. Jude Children’s Research Hospital, describing a partial response in the first patient with a TRK fusion cancer enrolled in the pediatric Phase 1 dose-escalation trial of LOXO-101. The 16-month old female patient with advanced infantile fibrosarcoma (IFS), a rare pediatric cancer, experienced a 90 percent tumor regression, and repeat scans showed continued decrease in tumor volume. As of the preparation of the manuscript, the patient was in study cycle 5 with a RECIST confirmed partial response, and was beginning to achieve normal developmental milestones.

LOXO-101 has shown objective partial responses in adult patients with tumors harboring TRK gene fusions in a Phase 1 trial. LOXO-101 is also being evaluated in a global Phase 2 multi-center basket trial in adult patients with solid tumors that harbor TRK gene fusions.

About LOXO-101
LOXO-101 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an ongoing Phase 1 clinical trial, LOXO-101 has demonstrated encouraging preliminary efficacy. LOXO-101 is also being evaluated in a global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions and a Phase 1 trial in pediatric patients. For additional information about the LOXO-101 clinical trials, please refer to www.clinicaltrials.gov or www.loxooncologytrials.com. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123.

Argos Therapeutics Enters into Strategic Research Agreement with Adaptive Biotechnologies

On June 15, 2016 Argos Therapeutics, Inc. (Nasdaq:ARGS), an immuno-oncology company focused on the development and commercialization of truly individualized immunotherapies for the treatment of cancer based on the Arcelis technology platform, reported that it is partnering with Adaptive Biotechnologies Corporation, based in Seattle, Washington, to study precise response patterns to Argos’ investigational immunotherapies (Press release, Argos Therapeutics, JUN 15, 2016, View Source [SID:1234513356]).

Under the agreement, Adaptive will use its patented immune profiling immunoSEQ Assay to enable a more in-depth characterization of the immune response induced by Argos’s lead product candidate, AGS-003, which is currently being studied in the treatment of metastatic renal cell carcinoma, non-small cell lung cancer, and bladder cancer. In addition, Argos is developing its second Arcelis product candidate, AGS-004, for the treatment and the possible eradication of human immunodeficiency virus (HIV) in patients with HIV-infection or acquired immune deficiency syndrome (AIDS). The application of Adaptive’s immune profiling technology in this setting will enable Argos to further characterize with greater precision the transfer of specific genetic signatures from each patient’s HIV, through AGS-004, to a specific immune response against each patient’s unique virus population.

"We are very excited to be entering into this important research agreement with Adaptive Biotechnologies," said Dr. Charles Nicolette, Argos’s chief scientific officer. "Adaptive is our preferred partner because of their established expertise in offering high-throughput immune receptor repertoire characterization and advanced bioinformatics that are ideally suited to analyze precision of target-specific immune activation enabled by Arcelis administration with higher resolution."

"Argos is on the cutting edge of precision immunotherapy with their advanced Phase 3 immuno-oncology agent, and platform extension into individualized HIV treatment," said Chad Robins, Adaptive’s president, chief executive officer and co-founder. "As the leader in immunosequencing, Adaptive’s technology is well-suited to uncover the dynamics of the adaptive immune system response to Argos’ therapies."

LTX-315 in two oral presentations at WPC in Boston 14-16 June 2016

On June 14, 2016 Lytix Biopharma In collaboration with Adaptive Biotechnologies (Seattle, USA), reported that they have investigated changes in T cell clonality before and after treatment of murine B16 melanomas with LTX-315 (Press release, Lytix Biopharma, JUN 14, 2016, View Source [SID:1234514841]). At the World Preclinical Congress to be held in Boston this week, Sharon Benzeno from Adaptive Biotechnologies will present data showing that LTX-315 significantly enhances T cell infiltration and T cell clonality in B16 melanomas. The results indicate that LTX-315 has the potential to convert non-T cell inflamed tumors into T-cell inflamed tumors. Since immunotherapy normally is more effective in subsets of patients with a T cell inflamed tissue, LTX-315 may increase the number of patients responding to immunotherapy. In collaboration with Oncodesign (Dijon, France) Lytix has shown promising results by combining LTX-315 and the immune checkpoint blockade inhibitor anti-PD-L1. Phillippe Slos from Oncodesign will present data demonstrating that LTX-315 in combination anti-PD-L1 enhance the delay of tumor growth compared to each compound alone in the murine mammary carcinoma model EMT-6.

World Preclinical Congress (WPC) is a key networking event for those involved in preclinical research and features conferences, training seminars and short courses that cover the very latest in preclinical strategies and technologies, to enable better and faster decisions in drug discovery.

Transgenomic Accelerates Commercialization of ICE COLD-PCR (ICP) amid Plans to Expand Cancer Product Line Ten-Fold

On June 14, 2016 Transgenomic, Inc. (TBIO), (NASDAQ: TBIO), reported plans to expand its ICE COLD-PCR (ICP)-powered cancer assays ten-fold over the next 18 months, targeting a portfolio of more than 200 exons/mutations expected to be available to partners, cancer researchers, drug developers and clinicians by 2018 (Press release, Transgenomic, JUN 14, 2016, View Source [SID:1234513324]). Multiplexed ICP technology’s ultra-high sensitivity down to 0.01% makes it possible to run ICP assays using either tissue, blood or serum samples on any sequencing platform. Recently-released studies indicate high concordance between ICP detection tests and assays produced using conventional technology, with the added benefit that the ICP tests detected mutations in both plasma and tissue samples that were missed by conventional methods.

The expanded ICP cancer test menu will be released over the course of the next 18 months, with about 10 new exons/mutations expected to be issued every 6-8 weeks. The new tests will available in several formats–for use by TBIO’s partners and licensees, through TBIO’s Biomarker Discovery Services group and Oncology CLIA laboratory, as well as through its ICEme kits, which customers can run on Sanger, NGS and other platforms in their own laboratories. The focus, as with TBIO’s current menu of detection tests and panels, will be on actionable mutations relevant to cancer treatment decisions, with priority given to mutations requested by customers along with those newly validated by cancer researchers. The company also intends to incorporate some of the added mutations into panels for use with specific cancers and tumor types.

TBIO President and CEO Paul Kinnon commented, "The rapidly growing use of genomic testing as an essential part of cancer treatment makes this a good time to build on the foundation we have created over the past year and to exponentially expand the menu of tumor exons/mutations that can be tested using our ICP technology. We have refined and industrialized the development of new tests, as we demonstrated with the recent rapid development and release of our EGFR C797S ICP assay. We therefore believe that our ambitious goal of offering more than 200 exons/mutations by 2018 is achievable. We are optimistic that the accuracy, versatility, ease of use and rapid turnaround of ICP cancer testing, along with its availability in multiple formats and on a variety of platforms, will generate strong demand as we expand the test menu. We look forward to working with a range of customers and diagnostic laboratory partners to apply the power of TBIO’s expanded ICP product line to accelerate cancer research and improve patient outcomes."

ICE COLD-PCR achieves its ultra-high sensitivity through selective amplification of mutant DNA. The result is up to a 500-fold increase in sensitivity in identifying mutations with the most precise sequence alteration detection rates available. ICP was originally developed by the laboratory of Dr. Mike Makrigiorgos at the Dana-Farber Cancer Institute, which has exclusively licensed rights to the technology to Transgenomic.