On October 23, 2018 Humanetics Corporation (Humanetics) reported that it has been invited to present at the annual meeting of the American Society for Radiation Oncology (ASTRO) being held October 21st through the 24th in San Antonio, Texas. Dr. Michael Kurman, M.D., Chief Medical Officer for Humanetics, will be presenting an overview of the study design and providing an update on the status of the Company’s on-going, multi-site, Phase 1b/2a trial in non-small cell lung cancer patients (Press release, Humanetics, OCT 23, 2018, View Source [SID1234530068]). The trial is investigating the safety and efficacy of BIO 300, a new drug candidate focused on mitigating toxicities to normal tissues resulting from cancer radiotherapy.

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Lung cancer is the most common cause of cancer-related deaths in the United States and affects more than 230,000 individuals per year. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, comprising approximately 87% of all cases. A common treatment for NSCLC is radiotherapy, which is often accompanied by chemotherapy. Radiation can cause unwanted side-effects to otherwise healthy tissue surrounding the tumor or in the path of the radiation beam. These effects include esophagitis, pulmonary pneumonitis and fibrosis, all of which can contribute to lasting health problems and in severe cases can be fatal.

"Drugs that can prevent the unwanted side effects of radiotherapy are an urgent need for patients," said Dr. Charles Simone, Associate Professor of Radiation Oncology and Medical Director of the Maryland Proton Therapy Center in Baltimore, Maryland. "Radiotherapy is an important standard of care and its use is forecast to grow. Drugs such as BIO 300 have the potential to significantly improve the quality of life and outcomes for our patients." Dr. Simone is serving as a Principal Investigator for the BIO 300 clinical trial.

BIO 300 is an oral medication, taken once daily by the patient prior to their radiation treatment. Its properties as a radioprotectant were discovered by researchers at the U.S. Department of Defense, where it was studied as a potential agent to be used by warfighters to prevent injury from radiation on the battlefield. Humanetics acquired the rights to the drug and has active development programs ongoing in both oncology and for biodefense.

On October 23, 2018 NextCure, Inc., a privately-held biopharmaceutical company discovering and developing next generation immunomedicines for cancer and other diseases, reported the initiation of a Phase 1/2 clinical trial for NC318, a Siglec-15 (S15) antibody (Press release, NextCure, OCT 23, 2018, View Source [SID1234530067]).

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The Phase 1 dose-escalation portion of this open-label trial will evaluate the safety and tolerability of NC318 in patients with advanced or metastatic solid tumors and determine its pharmacologically active and/or maximum tolerated dose. After a recommended dose for the Phase 2 portion of the trial is determined, the efficacy of NC318 will be evaluated in select tumor types. The trial is being conducted at five clinical sites in the United States. Details can be found at clinicaltrials.gov – NCT03665285.

"NC318 is the first antibody drug candidate developed at NextCure to enter clinical trials, marking an exciting milestone for our company," says Michael Richman, CEO of NextCure. "The trial marks a major advancement in our plan to develop our pipeline of next generation immunomedicines for cancer patients who do not respond to currently approved therapies."

S15 is a novel immunomodulatory target expressed on a restricted set of myeloid cells in the tumor microenvironment and on certain tumor types including lung, ovarian and head and neck cancers. Preclinical research shows that S15 promotes the survival and differentiation of suppressive myeloid cells and negatively regulates T cell function, allowing cancer growth. In preclinical studies, NC318 blocks the negative effects of S15. NC318 is a first-in-class immunomedicine that has the potential to treat multiple cancer types.

"Immunotherapies targeting T cell function have significantly improved patient outcomes; however, a substantial proportion of patients do not respond to currently approved PD-1 or PD-L1 antibody therapies," said Kevin N. Heller, M.D., CMO of NextCure. "Laboratory studies demonstrate that Siglec-15 modulates immune suppression in a manner independent of the PD-1/PD-L1 pathway, suggesting that NC318 may have the potential to be used in patients who do not express PD-L1. Blocking S15 with NC318 is expected to diminish immunosuppression and normalize the immune response, resulting in a clinically relevant anti-tumor immune response. A goal of our trial is to test that hypothesis."

The immune regulatory function of S15 was initially discovered in the lab of Lieping Chen, M.D., Ph.D., Founder of NextCure and United Technologies Endowed Professor of Cancer Research, Professor of Immunobiology, Dermatology, and Medicine at the Yale University School of Medicine. Dr. Chen is a renowned leader in immuno-oncology and has discovered many novel immune-related targets, including the PD-1/PD-L1 pathway. "The discoveries made by our group and others have paved the way for the first generation of immunotherapies, leading to major breakthroughs in cancer treatment. Building upon these early discoveries, and in collaboration with NextCure, we continue our research to identify new targets for modulating the immune system," stated Dr. Chen. "We expect that S15, one of the first new targets identified, will be the first in a series of next generation immunomedicines. Through a comprehensive and streamlined process, NextCure has efficiently brought NC318 to the clinic."

On October 23, 2018 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported financial results for the three and nine months ended September 30, 2018 (Press release, Odonate Therapeutics, OCT 23, 2018, View Source [SID1234530066]).

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As of September 30, 2018, Odonate had $161.0 million in cash, compared to $198.1 million as of December 31, 2017. This decrease in cash resulted primarily from net cash used in operating and investing activities of $45.3 million and $1.6 million, respectively, less net cash provided by financing activities of $10.1 million, which includes $9.8 million from the exercise of the underwriters’ option to purchase additional shares of common stock in our initial public offering. Odonate’s net loss for the three and nine months ended September 30, 2018 was $23.9 million and $60.2 million, or $0.98 per share and $2.47 per share, respectively, compared to $10.4 million and $17.0 million, or $0.74 per share and $1.37 per share, for the same periods in 2017, respectively.

About Tesetaxel

Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer. Tesetaxel has several pharmacologic properties that make it unique among taxanes, including: oral administration with a low pill burden; a long (~8-day) terminal plasma half-life in humans, enabling the maintenance of adequate drug levels with relatively infrequent dosing; no history of hypersensitivity (allergic) reactions; and significant activity against chemotherapy-resistant tumors. More than 500 patients have been treated with tesetaxel in clinical studies. In patients with metastatic breast cancer, tesetaxel was shown to have significant, single-agent antitumor activity in two multicenter, Phase 2 studies.

About CONTESSA

CONTESSA is a multinational, multicenter, randomized, Phase 3 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC). CONTESSA is comparing tesetaxel dosed orally at 27 mg/m2 on the first day of a 21-day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally on days 1-14 of a 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day dosed orally on days 1-14 of a 21-day cycle) in approximately 600 patients randomized 1:1 with HER2 negative, hormone receptor (HR) positive LA/MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in LA/MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. The primary endpoint is progression-free survival (PFS) assessed by an Independent Radiologic Review Committee (IRC). CONTESSA’s secondary efficacy endpoints are overall survival, objective response rate (ORR) assessed by IRC and disease control rate assessed by IRC. To learn more, please visit www.contessastudy.com.

On October 23, 2018 Incyte Corporation (Nasdaq: INCY) reported that it has released updated data from its ongoing Phase 2 FIGHT-202 trial for the evaluation of pemigatinib (INCB54828), its selective inhibitor of fibroblast growth factor (FGFR), in patients with metastatic or surgically unresectable cholangiocarcinoma in an advanced stage (cancer of the bile ducts) that did not respond to at least one previous treatment (Press release, Incyte, OCT 23, 2018, View Source [SID1234530065]). In patients with translocations of FGFR2 who were followed for at least eight months, the results of the intermediate study show a global response rate (ORR) of 40 percent, the main endpoint, and a progression-free survival (PFS) average of 9.2 months, a secondary endpoint.

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These results will be presented at the European Oncology Congress (ESMO) (Free ESMO Whitepaper) 2018, which is being held in Munich, Germany, in a poster presentation on Sunday, October 21 at 12:45 p.m., Spanish Peninsular Time, at 1:45 p.m. Spanish peninsular (6:45 am East Coast time at 7:45 am East Coast time). (Location: Hall A3 – Poster Area Networking Hub, summary # 756P)

"We are delighted to share with ESMO (Free ESMO Whitepaper) the updated intermediate results of our ongoing FIGHT-202 study, which underscore the potential of pemigatinib as a new effective treatment option for patients with advanced cholangiocarcinoma who have translocations of FGFR2," Steven Stein said. MD, medical director, Incyte. "If the full data set supports this, we hope to send a new application for new drug registration to the FDA in 2019 and obtain authorization for pemigatinib as the first selective inhibitor of FGFR of its kind to treat patients with advanced cholangiocarcinoma, a disease devastating ».

Cholangiocarcinoma is a cancer that arises from bile duct cells. It is often diagnosed late (phases III and IV) and the prognosis is unfavorable. It is more common in people older than 70 years, and more in men than in women. The FGFR2 fusion genes drive the onset of the disease, which occurs almost exclusively in patients with intrahepatic cholangiocarcinoma (iCCA), a subtype of the disease, and are present in up to 20% of iCCA patients. The incidence of cholangiocarcinoma with translocation of FGFR2 is growing and it is currently estimated that there are between 2,500 and 3,000 patients in the USA. UU., Europe and Japan.

Main results of FIGHT-202

The updated data, with longer-term follow-up, of the intermediate analysis presented today in the ESMO (Free ESMO Whitepaper) (with a cut-off date of July 24, 2018) show that, in advanced / metastatic or surgically unresectable iCCA patients with translocations of FGFR2 treated with pemigatinib that were followed up for at least eight months (cohort A, n = 47), the combined overall response rate (ORR) was 40%, including 19 patients (40%) with confirmed partial response and 21 patients ( 45%) with stable disease (SD). The combined disease control rate (CRD) was 85% (40/47). In addition, mean progression-free survival (PFS) was 9.2 months and mean overall survival (OS) was 15.8 months.

FIGHT-202: global response rates (ORR), disease control rates (DCR), response durability (DOR), progression-free survival (PFS), and overall survival (OS) per cohort of patients

Pemigatinib was tolerated well. The most common adverse events during treatment (TEAE) were hyperphosphatemia (61 percent), alopecia (42 percent), diarrhea (39 percent), decreased appetite (37 percent), and fatigue (36 percent). TEAEs of grade ≥ 3 (observed in> 5 percent of patients) were hyperphosphatemia (14 percent), hyponatremia (8 percent), abdominal pain (7 percent), and arthralgia (7 percent). Five patients experienced TEAE resulting in death, none of them related to the study treatment.

"I am greatly encouraged by the intermediate results of the FIGHT-202 study, which have shown significant clinical activity and a promising preliminary prediction of progression-free survival. As a practicing physician, I am excited about the potential of pemigatinib to provide a new treatment option for my patients with advanced cholangiocarcinoma, a deadly disease, "said Antoine Hollebecque, MD, Institute of Cancérologie Gustave Roussy, Villejuif, France.

About FIGHT-202

FIGHT-202 is a multicentre open-label study (NCT02924376) that evaluates the safety and efficacy of pemigatinib (INCB54828), a selective inhibitor of fibroblast growth factor receptor (FGFR), in the clinical research phase, potent and orally developed. by Incyte, in adult patients (age ≥18 years) with advanced / metastatic or surgically unresectable cholangiocarcinoma with known fibroblast growth factor (FGFR) / FGFR alterations and who have not responded to at least one previous treatment.

Patients were included in one of these three cohorts: cohort A (translocations of FGFR2), cohort B [other genetic alterations (GA) of FGF / FGFR] or cohort C (without GA of FGF / FGFR). All patients received 13.5 mg of pemigatinib orally once a day (QD) during a 21-day cycle (two weeks with treatment / one week without treatment) until the radiological progression of the disease or a level of toxicity unacceptable.

The main endpoint of FIGHT-202 is the overall response rate (ORR) in cohort A, independently assessed according to the RECIST v1.1 criteria. Secondary endpoints include ORR in cohorts B, C and A plus B, progression free survival (PFS), overall survival (OS), durability of response (DOR), disease control rate (DCR) and security.

Recruitment for the FIGHT-202 study was conducted entirely outside of Japan, and it is planned to present updated data for the second half of 2019. For more information on FIGHT-202, visit View Source show / NCT02924376 .

About FIGHT

Phase 2 studies investigating the safety and efficacy of monotherapy with pemigatinib in various neoplasms motivated by FGFR are underway. The FIGHT clinical trial program (FIbroblast Growth factor receptor in oncology and Hematology Trials) currently comprises the FIGHT-201 study in patients with metastatic or surgically unresectable bladder cancer, including activating alterations of FGFR3; the FIGHT-202 study in patients with metastatic or surgically unresectable cholangiocarcinoma who did not respond to previous treatment, including activating translocations of FGFR2; and the FIGHT-203 study in patients with myeloproliferative neoplasms with activating translocations of FGFR1.NCT03656536 ).

About the FGFR and Pemigatinib (INCB54828)

Fibroblast growth factor receptors (FGFR) play an important role in the proliferation of tumor cells and in survival, migration and angiogenesis (formation of new blood vessels). The mutations, translocations and activating gene amplifications of the FGFRs are closely correlated with the development of various types of cancer.

Pemigatinib is a potent selective inhibitor of isoforms 1, 2 and 3 of FGFR that, in preclinical studies, has shown a selective pharmacological activity against cancer cells with alterations in FGFR.

On October 23, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported that it has initiated an open-label, multicenter, Phase 1b/2 study of rebastinib in combination with paclitaxel to assess safety, tolerability, pharmacokinetics and efficacy in patients with advanced or metastatic solid tumors (Press release, Deciphera Pharmaceuticals, OCT 23, 2018, View Source [SID1234530064]).

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"We are excited to initiate this Phase 1b/2 clinical trial of rebastinib, our small molecule switch control inhibitor of TIE2," said Michael D. Taylor, Ph.D., Deciphera’s President and Chief Executive Officer. "In preclinical testing rebastinib has shown activity as a single agent and when combined with paclitaxel, we observed synergistic reductions in circulating tumor cells and ablating distant metastases. As a result, we believe rebastinib has the potential to be an important new therapy for cancer patients when combined with chemotherapy. In addition to the Phase 1b/2 clinical trial with paclitaxel, we intend to initiate a second Phase 1b/2 clinical trial of rebastinib in combination with carboplatin in the coming months."

In this two-part Phase 1b/2 clinical trial, rebastinib will be evaluated for the treatment of patients with advanced or metastatic solid tumors in combination with paclitaxel. Part 1 is designed to evaluate the safety, tolerability and pharmacokinetics of 50 mg and 100 mg rebastinib twice daily (BID) when administered in combination with paclitaxel, and to determine the recommended phase 2 dose (RP2D) of rebastinib in combination with paclitaxel, in patients with advanced or metastatic solid tumors that are refractory to standard therapies. In part 2, the safety, tolerability and efficacy of the RP2D of rebastinib in combination with weekly paclitaxel will be assessed across multiple cohorts, including: breast cancer, ovarian cancer, and endometrial cancer. This trial will enroll up to 36 evaluable patients in part 1 and up to 132 evaluable patients in part 2. For more information about the clinical trial design please visit www.clinicaltrials.gov (NCT03601897).

"There is an increasing understanding of the mechanisms by which tumors co-opt the surrounding microenvironment to grow, survive and become more invasive. TIE2 kinase is involved in multiple mechanisms favoring a pro-tumoral microenvironment, including the regulation of a population of immunosuppressive macrophages, promotion of tumor angiogenesis, and participation in perivascular pumps that lead to tumor cell intravasation and distal metastasis," said Oliver Rosen, M.D., Chief Medical Officer at Deciphera. "Certain of these macrophages express TIE2 and we believe selective inhibition of this kinase with rebastinib in combination with paclitaxel is a promising approach to treating these patients."

About Rebastinib
Rebastinib is an investigational, orally administered, potent and selective inhibitor of the TIE2 kinase, the receptor for angiopoietins, an important family of vascular growth factors in the tumor microenvironment that also activate pro-tumoral TIE2 expressing macrophages. In a Phase 1 clinical trial, biomarker data have demonstrated rebastinib-induced increases in the TIE2 ligand angiopoietin 2, secondary to TIE2 inhibition. Rebastinib is currently being evaluated in a Phase 1b/2 clinical trial in combination with paclitaxel (NCT03601897) and an investigator sponsored Phase 1b trial in patients with metastatic breast cancer in combination with paclitaxel or eribulin (NCT02824575).