On December 19, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported that the U.S. Food and Drug Administration (FDA) has approved FoundationFocus CDxBRCA for use as a companion diagnostic to aid in identifying women with ovarian cancer for whom treatment with Rubraca (rucaparib), a therapy developed by Clovis Oncology, Inc., is being considered (Press release, Foundation Medicine, DEC 19, 2016, View Source [SID1234517130]). FoundationFocus CDxBRCA is an FDA-approved tissue-based, genomic assay that uniquely detects tumor BRCA1 and BRCA2 mutations (may include both germline (inherited) and somatic (acquired)) in ovarian cancer. FoundationFocus CDxBRCA may help identify more women who could benefit from Rubraca therapy as compared to conventional testing methods that only identify germline BRCA1/2 mutations. Germline-only BRCA1/2 testing identifies approximately half of all BRCA1/2 mutations.i,ii

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Rubraca is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies, and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

"These simultaneous approvals by the FDA represent a step forward for women with advanced ovarian cancer, an area where there is a tremendous need for effective therapeutic approaches and efficient ways to identify those most likely to respond to PARP inhibitor therapy," said Michael Pellini, M.D., chief executive officer of Foundation Medicine. "This approval also represents a significant milestone for Foundation Medicine, one that underscores the quality and value of our molecular information solutions to inform patient care and to accelerate and streamline the therapeutic development programs of our biopharmaceutical partners."

Foundation Medicine and Clovis Oncology closely collaborated on a regulatory strategy to develop FoundationFocus CDxBRCA in parallel with the development of Rubraca. Tissue samples taken from individuals with ovarian cancer who enrolled in rucaparib clinical trials were analyzed by Foundation Medicine utilizing comprehensive genomic profiling (CGP) to identify biomarkers associated with a response to therapy. These molecular signatures of response informed the development of FoundationFocus CDxBRCA, which was utilized in Clovis’ pivotal trial, ARIEL2, to identify patients and accelerate recruitment into the study. The companies filed concurrent pre-market approval (PMA) and new drug application (NDA) submissions with the FDA earlier this year.

With this FDA approval, FoundationFocus CDxBRCA is the first validated, tissue-based assay developed from the Quality Systems Regulations (QSR)-compliant version of Foundation Medicine’s CGP assay, providing uniform analysis of all BRCA1/2 coding exons.

Dr. Pellini continued, "FDA approval of our first companion diagnostic assay also represents an important advance in our efforts to utilize our rigorously validated CGP approach to deliver a universal companion diagnostic assay. We believe this approach may enable the efficient delivery of personalized cancer care by eliminating the guesswork for physicians through a comprehensive view of companion diagnostic claims, as well as potential treatment options based on guidelines, peer reviewed literature and clinical trials."

As part of the company’s effort to develop a universal companion diagnostic, earlier this year, Foundation Medicine announced that FoundationOne, the company’s CGP assay for solid tumors, was accepted by the FDA and the Centers for Medicare and Medicaid Services (CMS) for Parallel Review. The FDA also granted Foundation Medicine’s request for review as part of its Expedited Access Pathway for breakthrough devices. If approved, FoundationOne would be an FDA-approved CGP assay that incorporates multiple companion diagnostics to support precision medicine in oncology, including an indication for use as a companion diagnostic across a diverse range of solid tumors, which is anticipated to include ovarian cancer.

More than 22,000 women will potentially be diagnosed with ovarian cancer in the U.S. during 2016.iii Ovarian cancer is the leading cause of female gynecologic cancer-related deathsiv and one in four women with ovarian cancer have a germline or somatic BRCA mutation.ii

About FoundationFocus CDxBRCA

Intended Use: FoundationFocus CDxBRCA is a next generation sequencing test for qualitative detection of BRCA1 and BRCA2 (BRCA1/2) alterations in formalin-fixed paraffin-embedded (FFPE) ovarian tumor tissue. The FoundationFocus CDxBRCA assay detects sequence alterations in BRCA1/2 genes. Results of the test are used as an aid in identifying ovarian cancer patients for whom treatment with Rubraca (rucaparib) is being considered. If a patient is positive for any of the deleterious alterations specified in the BRCA1/2 classification, the patient may be eligible for treatment with Rubraca. This assay is to be performed at Foundation Medicine, Inc., a single laboratory site located at 150 Second Street, Cambridge, MA 02141. For more information about FoundationFocus CDxBRCA assay, visit View Source

On December 18, 2016 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported updated results from its adult Phase 1 open-label, dose-escalation trial of larotrectinib (LOXO-101), a selective inhibitor of tropomyosin receptor kinase (TRK) (Press release, Loxo Oncology, DEC 18, 2016, View Source [SID1234517096]). The data were presented today at the 2016 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress in Singapore. Data from this ongoing Phase 1 trial were last reported at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2016.

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As of a November 10, 2016 data cutoff, 59 patients with refractory solid tumors had been enrolled and treated with single agent larotrectinib, including eight patients with cancers harboring TRK fusions. Seven patients with TRK fusion cancers were on study sufficiently long for an efficacy assessment, while an eighth TRK fusion patient had been recently enrolled and was not yet evaluated for response. Six of the seven efficacy evaluable patients achieved a confirmed partial response, as defined by standard RECIST criteria. The seventh patient, as previously reported, demonstrated clear radiographic tumor regressions, including in the central nervous system, and remains on study, but had not met the threshold required for a RECIST response. All responders remained in response, with one patient in cycle 22, one patient in cycle 19, one patient in cycle 18, two patients in cycle 15 and one patient in cycle 11. Each cycle is 28 days, or approximately one month.

Larotrectinib has been well tolerated at doses that include and exceed the recommended Phase 2 dose of 100 mg BID. A maximum tolerated dose (MTD) has not been defined. The majority of adverse events reported by the investigators have been mild to moderate.

"The depth of responses and durability data with larotrectinib in patients with TRK fusion cancers are among the most promising that we see in oncology Phase 1 clinical trials," said Todd Bauer, M.D., associate director, drug development and principal investigator, Sarah Cannon Research Institute and presenter of the larotrectinib oral presentation. "We believe our patients would benefit from the addition of larotrectinib to the armamentarium of matched targeted therapies for our patients, as our continued utilization of molecular testing in clinical practice will naturally lead to the identification of patients with TRK fusions."

"We continue to be very pleased with the efficacy and safety data we are seeing across the larotrectinib program," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "We look forward to further evaluating larotrectinib in adults with TRK fusion cancers in our Phase 2 NAVIGATE study and in pediatric patients in the SCOUT Phase 1/2 study, and sharing those data publicly over time."

Larotrectinib (LOXO-101) Phase 1 Results
Larotrectinib is currently being evaluated in an ongoing dose-escalation Phase 1 trial in patients with solid tumors refractory to standard therapy. As of November 10, 2016, 59 patients with advanced cancer had been treated at six dose levels: 50 mg QD, 100 mg QD, 100 mg BID, 150 mg BID, 200 mg QD and 200 mg BID. The median age of these patients is 59 (ranging from 19-82) and the median number of prior treatments is three (ranging from 0-24).

Safety Analysis
Larotrectinib has been well tolerated in the 59 patients treated, including 34 patients at a dose of 100mg BID. Adverse events reported regardless of attribution to study drug are generally consistent with those previously presented. The most common adverse events, largely Grade 1 and 2, include fatigue (37 percent), dizziness (29 percent), anemia (25 percent) and dyspnea (25 percent). No individual Grade 3 or 4 adverse events occurred in more than three patients treated at 100mg BID or more than five patients in the entire study population. The frequency of toxicities did not correlate with dose level. The MTD has not yet been defined.

Efficacy Analysis
As of November 10, 2016, eight patients with cancers harboring TRK fusions had been enrolled, representing a broad range of tumor types, namely mammary analogue secretory cancer of the salivary glands (MASC, n=3), gastrointestinal stromal tumor (n=2), soft tissue sarcoma, thyroid carcinoma and non-small cell lung cancer. Seven patients with TRK fusion cancers were on study sufficiently long for an efficacy assessment, while an eighth TRK fusion patient had been recently enrolled and was not yet evaluated for response. Six of the seven efficacy evaluable patients achieved a confirmed partial response, as defined by standard RECIST criteria. A seventh patient, as previously reported, demonstrated clear radiographic tumor regressions, including in the central nervous system, and remains on study, but had not met the threshold required for a RECIST response. All responders remained in response, with one patient in cycle 22, one patient in cycle 19, one patient in cycle 18, two patients in cycle 15 and one patient in cycle 11. Each cycle is 28 days, or approximately one month.

On Monday, December 19, 2016, Loxo Oncology plans to file a Form 8-K with the U.S. Securities and Exchange Commission (SEC) containing the larotrectinib materials presented at the ESMO (Free ESMO Whitepaper) Asia meeting. These materials will also be posted to the Loxo Oncology website.

About Larotrectinib (LOXO-101)
Larotrectinib (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, larotrectinib has demonstrated encouraging preliminary efficacy. Larotrectinib is also being evaluated in the NAVIGATE global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions, and the SCOUT Phase 1/2 trial in pediatric patients, including patients with advanced cancer, TRK gene fusions and infantile fibrosarcoma. Larotrectinib has been granted Breakthrough Therapy Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

On December 16, 2016 Redx Pharma Plc is pleased to announce that it has presented the pre-clinical profile of its reversible Bruton’s tyrosine kinase (BTK) inhibitor RXC005 at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California, United States, on 5 December 2016 (Press release, Redx Pharma, DEC 16, 2016, View Source [SID1234524745]).

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Redx’s development candidate RXC005 is a novel, potent and selective, reversible BTK inhibitor with efficacy and equivalent potency against wild-type and cysteine-481 (C481) mutated BTK. First generation BTK inhibitors, such as Ibrutinib and Acalabrutinib, specifically target C481 within BTK and mutations at this site interfere with covalent drug binding. Several mutations have been reported and linked to cases of resistance that have emerged in patients with chronic lymphocytic leukaemia (CLL) progression following treatment with Ibrutinib. Redx’s reversible BTK inhibitor RXC005 aims to overcome this resistance mechanism by targeting both wild type and C481-mutated BTK.

The Company is progressing studies to prepare the RXC005 program for first-in-human clinical trials. The aim is to commence these trials late 2017.

Dr Neil Murray, CEO of Redx, said: We’re delighted to have presented the compelling pre-clinical profile of our reversible BTK inhibitor RXC005 at the ASH (Free ASH Whitepaper) 2016 meeting in San Diego.

RXC005 has the potential to become a potent therapy for chronic lymphocytic leukaemia patients by tackling the growing resistance to Ibrutinib treatment. We aim to initiate first-in-human clinical studies for RXC005 late 2017.

Further Details:
American Society of Hematology web site: View Source
Poster title: RXC005 (REDX08608), a Novel, Potent and Selective, Reversible BTK Inhibitor with Efficacy and Equivalent Potency Against Wild-Type and Mutant C481S BTK
Download the presentation poster: RXC005 (REDX08608) BTK Inhibitor

On December 13, 2016 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, and the Genome Institute of Singapore (GIS), a research institute under Singapore’s Agency for Science, Technology and Research (A*STAR), reported the execution of a research collaboration agreement to advance Atreca’s high-throughput, microfluidic technology for single-cell, sequence-based analyses of human immune responses, critical in the discovery and development of immuno-oncology therapeutics (Press release, Atreca, DEC 16, 2016, View Source [SID1234522959]).

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Co-funded by A*STAR and Atreca, and involving Atreca’s Singapore subsidiary, Atreca Pte. Ltd., this research effort will establish a joint lab at the GIS facility in Singapore’s Biopolis campus to add new capabilities to Atreca’s microfluidic technology for next-generation sequence analysis of expressed genes in single cells. These capabilities will include identification of genes for immunoglobulin superfamily members, such as antibodies and T cell receptors (TCRs), as well as other genes in B and T cells that play important roles in directing the body’s immune response towards cancer and pathogens, such as bacteria and viruses. The ability to analyze these genes is expected to pave the way for more targeted and effective immunotherapies. Yann Chong Tan, Ph.D., Co-Founder of Atreca, Inc., and an A*STAR scholar, will head the Atreca-GIS Joint Laboratory.

"This collaboration with GIS will facilitate advancing our state-of-the-art technology for analyzing human and model system immune responses, a capability that is central to Atreca’s therapeutic focus in immuno-oncology," commented Tito A. Serafini, Ph.D., Atreca’s President, Chief Executive Officer, and Co-Founder. "GIS offers a world-class research environment, bringing together leading expertise in next-generation sequencing, molecular cytogenetics, bioinformatics, and single cell genomics, and we are delighted to work with them on this effort."

Prof. Ng Huck Hui, Executive Director of GIS, stated, "We welcome the opportunity to partner with Atreca. This will see significant advancements in our research, including in precision medicine and infectious diseases, and further our collaborative work with the clinical community to offer therapeutic answers directly to patients."

On December 16, 2016 Aptevo Therapeutics Inc. (Nasdaq:APVO) a biotechnology company focused on developing novel oncology and hematology therapeutics, reported the publication of positive data from a Phase 2 clinical trial evaluating its proprietary humanized monospecific anti-CD37 protein therapeutic, otlertuzumab (Press release, Aptevo Therapeutics, DEC 16, 2016, View Source;p=irol-newsArticle&ID=2230353 [SID1234517094]). The results were recently published in the British Journal of Haematology (BJH).

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"We’re very encouraged by the Phase 2 data, which demonstrated a significant increase in median progression free survival, from approximately 10 to 16 months in patients receiving combination otlertuzumab/bendamustine therapy," said Marvin L. White, President and Chief Executive Officer. "These data, coupled with additional results from ongoing studies of otlertuzumab used in combination with current CLL therapies should help position otlertuzumab for a potential partnership to advance into Phase 3 clinical development."

The publication, entitled, "Randomized Phase 2 Study of Otlertuzumab and Bendamustine Versus Bendamustine in Patients with Relapsed Chronic Lymphocytic Leukemia," discusses the results of a multi-center Phase 2 clinical trial comparing the efficacy and safety of otlertuzumab in combination with bendamustine to bendamustine alone in patients with relapsed chronic lymphocytic leukemia (CLL). The data show an improved overall response rate and progression free survival with combination otlertuzumab/bendamustine therapy.

"While substantial advances in the treatment of CLL have been made over the last several years, there is still a significant unmet medical need for safe and effective new combination therapies to treat the many CLL patients that eventually will experience a relapse or discontinue therapy due to adverse events," remarked Dr. Scott Stromatt, Chief Medical Officer for Aptevo. "These latest data show the combination of otlertuzumab and bendamustine is well tolerated and significantly increases the response rate and PFS in patients with relapsed or refractory CLL. Consequently we are now exploring the utility of otlertuzumab in combination with additional CLL therapies to evaluate clinical benefit in distinct CLL patient subgroups."

The data published in BJH suggest that combination therapy with otlertuzumab may improve outcomes for CLL patients. In previous studies Aptevo has shown that otlertuzumab in combination with rituximab, obintuzumab or idelalisib is clinically active and appears to have a good safety and tolerability profile. Based on this promising body of data, Aptevo is further exploring its utility in subgroups of CLL patients who have either (i) not achieved a complete response after one year of therapy with ibrutinib, or (ii) in patients who are developing a resistant clone to ibrutinib but have not yet experienced a clinical relapse.

About the Phase 2 Clinical Trial
A total of 65 patients participated in the study with 32 receiving a combination of otlertuzumab and bendamustine and 33 receiving bendamustine alone. The primary endpoint in the clinical trial was overall response rate (ORR), as measured by the 2008 International Workshop on CLL. Secondary endpoints included an assessment of progression free survival (PFS) and safety.

Phase 2 Clinical Trial Results
The study demonstrated that otlertuzumab combined with bendamustine significantly increased overall response rate, which was 69% for the combination compared to 39% for bendamustine alone (p=0.025). In addition, the combination showed an improvement in median progression free survival, which was 15.9 months in the otlertuzumab/bendamustine combination treatment arm compared to 10.2 months in the bendamustine treatment arm (p=0.0192). Otlertuzumab in combination with bendamustine was generally well tolerated, although there was a higher incidence of pyrexia (34% vs. 12%) and neutropenia (59% vs. 39%) with the combination, however, this did not result in a higher incidence of severe (grade 3 or 4) infections.

The full publication in the British Journal of Haematology can be accessed online at View Source