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 19, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, and Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported that they have entered into a staged collaboration to evaluate, develop, and commercialize next-generation T-cell therapies (Press release, Adaptimmune, DEC 19, 2016, View Source [SID1234631816]).

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Under the agreement, the companies will evaluate Bellicum’s GoTCR technology (inducible MyD88/CD40 co-stimulation, or iMC) with Adaptimmune’s affinity-optimized SPEAR T-cells for the potential to create enhanced TCR product candidates. Depending on results from the preclinical proof-of-concept phase, the companies expect to progress to a two-target co-development and co-commercialization phase.

"We are committed to advancing our clinical pipeline of proprietary cell therapies and to entering strategic collaborations that can further leverage the unique potential of our controllable T-cell technologies," commented Tom Farrell, President and Chief Executive Officer of Bellicum. "We’re looking forward to working with the Adaptimmune team to create and advance potentially best-in-class TCR therapies."

"As we advance our deep pipeline of second- and third-generation SPEAR T-cell therapies, we are excited by the potential of Bellicum’s iMC switch to complement the activity of our affinity enhanced T-cell therapies, as part of our continuing initiative to assess novel cell therapy enhancement technologies," said James Noble, Adaptimmune’s Chief Executive Officer. "This is an innovative field that requires broad, industry-wide collaborations, such as our relationship with Bellicum and its strong leadership position in switch technology."

About Bellicum’s iMC Technology
Bellicum’s Chemical Induction of Dimerization (CID) technology platform was designed to address the challenges of current cellular immunotherapies by enabling control over cellular activities and functions, such as growth, activation, proliferation, persistence and survival. Bellicum’s CID platform consists of molecular switches—modified forms of signaling proteins—which are triggered inside the patient by infusion of small molecule rimiducid, instead of by natural upstream signals. Current product candidates incorporate either the CaspaCIDe safety switch, or iMC activation switch. After rimiducid is administered, CaspaCIDe is designed to trigger programmed cell death, or apoptosis, and iMC is designed to drive proliferation, activation and/or persistence of T-cells.

About Adaptimmune’s TCR Technology
Adaptimmune’s proprietary SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell receptor (TCR) technology enables the Company to genetically optimize TCRs in an effort to equip them to recognize and bind cancer antigens that are presented in small quantities on the surface of a cancer cell, whether of intracellular or extracellular origin, thus initiating cell death. The Company’s differentiated, proprietary technology allows it to reliably generate parental TCRs to naturally presented targets, affinity optimize its TCRs to bind cancer proteins from solid and hematologic cancers that are generally unavailable to naturally occurring TCRs, and to significantly reduce the risk of side effects resulting from off-target binding of healthy tissues.

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 Celsion Corporation (NASDAQ:CLSN) reported an update on its Phase III OPTIMA program for ThermoDox, Celsion’s proprietary heat-activated liposomal encapsulation of doxorubicin in combination with radiofrequency ablation (RFA) in primary liver cancer, also known as hepatocellular carcinoma (HCC) (Press release, Celsion, DEC 16, 2016, View Source [SID1234517095]). The Phase III OPTIMA Study is expected to enroll up to 550 patients at up to 75 clinical sites in the United States, Europe, China and Asia Pacific, and will evaluate ThermoDox in combination with optimized RFA, which will be standardized to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimeters, versus standardized RFA alone.

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The Company recently met with the China Food and Drug Administration (CFDA) to discuss the ongoing Phase 3 OPTIMA program and regulatory pathway for ThermoDox in China. During the meeting, Celsion presented the final overall survival data from the Chinese patient cohort of the HEAT study, which demonstrated a survival benefit in patients treated with ThermoDox plus optimized RFA versus optimized RFA alone. The CFDA informed Celsion that if the ongoing Phase 3 OPTIMA trial is successful, the trial could serve as the basis for a direct regulatory filing in China without the need to file for prior approval in the U.S. or European Union which is currently required for foreign company application. This would allow the Company to accelerate its plans for a regulatory filing in China and, if approved, provide for a significantly earlier launch date in China than originally expected.

"We are building momentum with our efforts for ThermoDox in the Asia Pacific region, particularly China, which represents a significant market opportunity with over 50% of new diagnosed cases of this devastating cancer," stated Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "All Chinese sites will be fully activated by early 2017, enrollment is on pace to meet our objective of fully enrolling the trial by the first quarter of 2018, and we have advanced our manufacturing in China with Hisun to support a potential future launch in this region with impressive gross margins. We believe that the remarkable data from the Chinese cohort of the HEAT study underscores the potentially curative nature of ThermoDox in patients with primary liver cancer, and we are pleased that the CFDA has both recognized its potential and offered a straightforward path to a regulatory filing in China."

In support of its efforts in China, Celsion reported that recent bioequivalence studies of ThermoDox produced in China by Hisun are equivalent to batches of ThermoDox produced at its United States manufacturing site.

In addition, Celsion reported that the Company’s management team recently met with the Ministry of Health in Vietnam and based on that meeting, it will move forward with launching additional trial sites for the OPTIMA study in the country. Celsion expects to have approximately 5 additional clinical trial sites in Vietnam activated by early 2017. Vietnam represents a significant market for ThermoDox where HCC incidence rates are among the world’s highest.

About the OPTIMA Study
The Phase III OPTIMA Study is expected to enroll up to 550 patients in up to 75 clinical sites in the United States, Europe, China and Asia Pacific, and will evaluate ThermoDox in combination with optimized RFA, which will be standardized to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimeters, versus standardized RFA alone. The primary endpoint for the trial is Overall Survival, which is supported by post-hoc analysis of data from the Company’s 701 patient HEAT Study, where optimized RFA has demonstrated the potential to significantly improve survival when combined with ThermoDox. The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee (iDMC).

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