On October 23, 2018 Context Therapeutics reported Phase 1 data for its investigational new drug, Apristor (Onapristone extended release), an oral progesterone receptor antagonist that is being developed for progesterone receptor-positive (PR+) cancers (Press release, Context Therapeutics, OCT 23, 2018, View Source [SID1234530069]). Data from the study showed that Apristor, a novel extended release formulation of onapristone, was well tolerated and provided a clinical benefit in patients with previously treated recurrent or metastatic progesterone receptor-driven breast, ovarian and endometrial cancers. These findings were published in the medical journal PLOS One and can be accessed here.

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"I’m encouraged by the early data seen in this Phase 1 study of Apristor. Apristor appears to be well tolerated, with responses seen across a broad range of PR+ cancers," commented Paul Cottu, M.D., Ph.D., Deputy Head, Department of Oncology, Institute Curie, and lead investigator for the trial. "Many hormonally-driven malignancies are difficult to treat, and new agents are clearly needed. Targeted therapies, including Apristor, have the potential not only to add therapeutic options for our patients but also to reduce or delay the need for chemotherapy, possibly changing the way many of these malignancies are treated."

"Context is pleased with the Phase 1 Apristor study results demonstrating clinical efficacy across PR+ cancers in heavily pretreated patients who are typically unresponsive to currently approved hormonal treatments," stated Martin Lehr, CEO of Context Therapeutics. "We believe Apristor has the potential to be the first anti-progestin approved to treat cancer and we are rapidly advancing Apristor into multiple Phase 2 trials with a goal of addressing significant medical needs."

Apristor Phase 1 Data in Patients with PR+ Breast, Ovarian, or Endometrial Cancer

Design
52 patients were randomized to five cohorts of Apristor (onapristone extended release tablets 10, 20, 30, 40 or 50 mg BID; n=46), or immediate release onapristone 100 mg QD (n=6) until progressive disease or intolerability. Primary endpoint was to identify the recommended phase 2 dose. Secondary endpoints included safety, clinical benefit and pharmacokinetics.

Results
Tumor diagnosis includes: endometrial carcinoma 12; breast cancer 20; ovarian cancer 13; and other 7. Median age was 64 (36-84). No dose limiting toxicity was observed with reported liver function test elevation related only to liver metastases. The recommended Phase 2 dose (RP2D) was 50mg BID. For patients on Apristor (n=46), dose responsive activity was noted, and 20% (9 of 46) patients had clinical benefit ≥24 weeks. The most common side effects were asthenia and low-grade, transient gamma-glutamyl transferase elevations.

Clinical Activity
Tumor assessments strongly suggested anti-cancer efficacy, even in heavily pretreated patients. In Apristor treated patients, 20 of 46 patients experienced stable disease as best response and 9 of 46 patients had durable disease stabilization.

The new extended release formulation of Onapristone (Apristor) was well tolerated and resulted in clinical benefit in heavily pretreated patients with ovarian, breast and uterine endometrial cancers. The recommended Phase 2 dose for Apristor is 50mg BID. There were no grade 3-4 LFT elevations in the absence of progressive liver metastases, no new safety signals were observed, and dose limiting toxicity was not observed. The data support the development of Apristor in PR+ cancers.

About Apristor

Apristor, an investigational new drug, is an oral progesterone receptor (PR) antagonist. PR is an oncogene that is enriched in up to 70% of all breast, ovarian, and endometrial cancers. Apristor is being developed to treat metastatic breast, ovarian and endometrial cancers.

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.