On October 18, 2017 XBiotech Inc. (NASDAQ:XBIT) reported enrollment of the first patient into a Phase I single arm study evaluating the maximum tolerated dose of OnivydeⓇ (Irinotecan liposome injection) and 5-fluorouracil/folinic acid in combination with MABp1 in a cohort of patients with advanced pancreatic adenocarcinoma and cachexia (Press release, XBiotech, OCT 18, 2017, View Source [SID1234521016]). The patient has begun treatment at Cedars-Sinai Medical Center under the care of Dr. Andrew Hendifar, the Study’s Principle Investigator, Medical Oncology lead for the Gastrointestinal Disease Research Group and Co-Director of Pancreas Oncology at Cedars-Sinai. A total of 16 patients are expected to be enrolled in the study.

Dr. Hendifar commented, “We are excited to enroll our first patient in this novel combinatorial therapy for the treatment of advanced pancreatic cancer and cachexia. This is the first attempt to add an anti-inflammatory therapy to standard chemotherapy in an effort to improve the performance, quality of life, and survival in patients with this disease.”

The study will also assess overall and progression free survival as well as evaluate the relationship between treatment tolerance and patient functional status. Various secondary measures, including changes in lean body mass, weight stability and levels of systemic inflammation will also be monitored. Onivyde will be given intravenously with MABp1 and 5-fluorouracil/folinic acid every two weeks until disease progression.

The prognosis for advanced pancreatic cancer remains poor despite decades of studies [1]. The 5-year survival has remained close to 5%, unchanged despite improvements in chemotherapeutics, surgical outcomes, and diagnostic techniques [1, 2]. Other than multi-agent cytotoxic therapy there have been no treatment advances for pancreatic cancer or its associated cachexia.

MABp1 was found to improve clusters of symptoms that included reduced pain, fatigue, improved appetite and increased lean body mass in advanced cancer patients. Patients that had these improvements were found to have less tumor progression, substantial reduced serious adverse events related to disease, and about a three-fold improvement in survival [3].

About True Human Therapeutic Antibodies
XBiotech’s True Human antibodies are derived without modification from individuals who possess natural immunity to certain diseases. With discovery and clinical programs across multiple disease areas, XBiotech’s True Human antibodies have the potential to harness the body’s natural immunity to fight disease with increased safety, efficacy and tolerability.

On October 18, 2017 Radius Health, Inc. (“Radius” or the “Company”) (Nasdaq:RDUS), reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for elacestrant, an investigational oral selective estrogen receptor down-regulator/degrader (SERD) as a treatment of women with ER+ and HER2- advanced or metastatic breast cancer (Press release, Radius, OCT 18, 2017, View Source [SID1234521010]). Fast Track designation is a process designed to facilitate the development and expedite the review of new therapies to treat serious conditions and fill unmet medical needs.

“It is estimated that about 1 in 8 women will develop invasive breast cancer over the course of their lifetime,” said Jesper Høiland, President and Chief Executive Officer of Radius Health. “If approved, elacestrant could offer a hormonal therapy alternative and potentially delay the use of chemotherapy in patients with estrogen receptor positive breast cancer. Early results of our Phase 1 trial show an encouraging efficacy and safety profile. We look forward to working closely with the FDA as we rapidly advance the development of elacestrant.”

The elacestrant clinical development program is currently ongoing with two Phase I studies in patients with ER+, HER2- advanced or metastatic breast cancer who have been heavily pre-treated (median of three prior lines of therapy) and have evaluable disease.

“The Company will provide updates on both Phase 1 studies and present two preclinical posters at the 2017 San Antonio Breast Cancer Symposium in December,” said Gary Hattersley, PhD, Chief Scientific Officer. “The FDA has indicated that, depending on the Phase 2 study results, the single-arm Phase 2 trial could be considered a pivotal study with a confirmatory study on-going at the time of NDA submission. We expect to enroll the first patient in the Phase 2 study in early 2018.”

For more information on ongoing clinical trials of elacestrant, visit www.clinicaltrials.gov.

On October 18, 2017 (GLOBE NEWSWIRE) — Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that the U.S. Food and Drug Administration (FDA) has accepted its supplementary premarket approval (sPMA) application for BRACAnalysis CDx to be used as a companion diagnostic with AstraZeneca’s PARP inhibitor Lynparza (olaparib) in patients with HER2-negative metastatic breast cancer (Press release, Myriad Genetics, OCT 18, 2017, View Source [SID1234521008]). Myriad expects the FDA’s priority review process to conclude in the fiscal third-quarter 2018.

Myriad’s sPMA filing follows positive results from the Phase III OlympiAD trial, which demonstrated that Lynparza significantly reduced the risk of disease progression or death in patients with BRCA-mutated, HER2-negative metastatic breast cancer by 42 percent compared to standard therapy. The results of the OlympiAD trial were published in the New England Journal of Medicine in June.

“The acceptance of the sPMA for BRACAnalysis CDx is a significant step towards enabling personalized medicine for patients with metastatic breast cancer,” said Mark C. Capone, president and CEO, Myriad Genetics. “As the pioneer in companion diagnostics for PARP inhibitors, we are excited to once again partner with AstraZeneca and broaden access to Lynparza for even more patients.”

If approved, BRACAnalysis CDx would be the first and only FDA-approved companion diagnostic for use with a PARP inhibitor to identify HER2-negative metastatic breast cancer patients with a BRCA mutation who would benefit from a PARP inhibitor. The Company estimates there are approximately 125,000 patients with metastatic breast cancer who would immediately qualify for the BRACAnalysis CDx test, followed by 60,000 new patients per year on an ongoing basis.

The ongoing collaboration with AstraZeneca to develop a novel companion diagnostic test to identify candidates for treatment with olaparib began in 2007. In Dec. 2014, Myriad received FDA approval for BRACAnalysis CDx to help identify patients with advanced ovarian cancer who are eligible for fourth-line treatment with olaparib. BRACAnalysis CDx is Myriad’s first FDA-approved companion diagnostic and was the first-ever laboratory developed test approved by the FDA.

About BRACAnalysis CDx
BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR.

Results of the test are used as an aid in identifying ovarian cancer patients with deleterious or suspected deleterious germline BRCA variants eligible for fourth line treatment with Lynparza (olaparib). This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108.

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. Lynparza is currently approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It also is approved in the United States for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy and for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. Lynparza is currently being investigated in another separate non-metastatic breast cancer Phase III study called OLYMPIA. This study is still open and recruiting patients internationally. In July 2017, AstraZeneca and Merck & Co., Inc., announced a global strategic oncology collaboration to jointly develop and commercialize AstraZeneca’s Lynparza, the world’s first and leading PARP inhibitor.

On October 18, 2017 Moleculin Biotech, Inc., (NASDAQ: MBRX) (“Moleculin” or the “Company”), a clinical stage pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported that 14 qualified cancer clinics have requested to participate in its clinical trial to study Annamycin for the treatment of relapsed or refractory acute myeloid leukemia (“AML”) (Press release, Moleculin, OCT 18, 2017, View Source [SID1234521006]).

“We’ve had a very positive response from the hematology oncology community,” commented Walter Klemp, Chairman and CEO of Moleculin. “With little to no cardiotoxicity and a structure that has been shown to avoid the multidrug resistance mechanisms that often defeat the current first line standard of care for AML, a number of clinicians recognize that Annamycin could provide a second chance to patients who have run out of options.”
Mr. Klemp continued: “We are pleased to have so many sites express interest in this trial, as it should help improve our chances for timely patient recruitment. In addition, seven of these interested sites are in Poland where we believe we will have access to a higher percentage of patients who are what we call ‘treatment naive’, meaning they have not been subjected to any experimental therapies before entering our trial.

On October 18, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported top-line overall response rate (ORR) results from the independent review committee assessment of the larotrectinib dataset (Press release, Loxo Oncology, OCT 18, 2017, View Source [SID1234521005]). The full dataset is being reserved for a future publication. Consistent with prior guidance, Loxo Oncology expects to submit a New Drug Application (NDA) for evaluation by the U.S. Food and Drug Administration (FDA) in late 2017 or early 2018, and a Marketing Authorisation Application (MAA) for evaluation by the European Medicines Agency (EMA) in 2018.

“Today’s results have exceeded our expectations, and confirm the depth and breadth of response larotrectinib delivers to patients with TRK fusion cancers,” said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. “We are indebted to our investigators and team members, whose care and sophistication in the execution of the larotrectinib clinical development program have now been validated by independent review.”

The following table compares response determinations between the independent review committee and investigators, using a July 17, 2017 data cut-off date:

Independent Review
Committee Assessed
Response (n=55) Investigator Assessed
Response
(n=55)
Overall Response Rate
(ORR = PR+CR) 75%
(95% CI: 61% – 85%) 80%*
(95% CI: 67% – 90%)
Partial Response (PR) 62 % 64%*
Complete Response (CR) 13 % 16 %
Stable Disease 13 % 9 %
Progressive Disease 9 % 11 %
Not Evaluable 4 % 0 %
* Includes one unconfirmed partial response, as of July 17, 2017, which was subsequently confirmed.

Consistent with global written regulatory correspondence, the NDA/MAA dataset includes adult and pediatric tropomyosin receptor kinase (TRK) fusion patients enrolled in Loxo Oncology’s Phase 1 adult trial, Phase 2 trial (NAVIGATE), and Phase 1/2 pediatric trial (SCOUT). The dataset is based on the intent to treat (ITT) principle, using the first 55 TRK fusion patients with RECIST-evaluable disease enrolled to the three clinical trials, regardless of prior therapy or tumor tissue diagnostic method. The primary endpoint for the integrated analysis of efficacy is overall response rate (ORR) according to the independent review committee assessment, as measured by RECIST v1.1. A key secondary endpoint is ORR according to local investigator assessment, as measured by RECIST v1.1.

The larotrectinib adverse event profile is consistent with data previously presented publicly.

The larotrectinib program has continued to enroll and treat newly identified patients with TRK fusion cancers, beyond the 55 patients described above. The anti-tumor activity and safety of larotrectinib in these additional patients are consistent with data reported today and previously. Notably, no new patients with CNS metastases have been identified or treated in any setting.

About Larotrectinib (LOXO-101)
Larotrectinib 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 analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated a 75 percent independently-reviewed confirmed overall response rate (ORR) and an 80 percent investigator-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib has been granted Breakthrough Therapy Designation Rare Pediatric Disease Designation and Orphan Drug 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.

About TRK Fusion Cancer
TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.