On October 31, 2017 Geron Corporation (Nasdaq:GERN) reported that the United States Food and Drug Administration (FDA) has granted Fast Track designation to imetelstat for the potential treatment of adult patients with transfusion-dependent anemia due to Low or Intermediate-1 risk myelodysplastic syndromes (MDS) who are non-del(5q) and who are refractory or resistant to treatment with an erythropoiesis stimulating agent (ESA) (Press release, Geron, OCT 31, 2017, View Source [SID1234521343]). Imetelstat is a telomerase inhibitor initially developed by Geron and exclusively licensed to Janssen Biotech, Inc. (Janssen) on a worldwide basis. Janssen sponsored the application for Fast Track designation utilizing preliminary data from IMerge, the ongoing clinical trial being conducted by Janssen in lower risk MDS.

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The FDA’s Fast Track Program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious conditions and supported by data that demonstrate the potential to address an unmet medical need. Fast Track designation provides opportunities for frequent interactions with FDA review staff, including meetings to discuss the drug’s development plan and to ensure the collection of appropriate data needed to support approval. Through the Fast Track Program, a product candidate may be eligible for priority review, if supported by the clinical data, and for the ability to submit completed sections of a New Drug Application (NDA) on a rolling basis as data become available prior to completion of the full application.

Imetelstat Clinical Development in MDS

Imetelstat is being evaluated in an ongoing Phase 2/3 clinical trial (IMerge) in transfusion dependent patients with Low or Intermediate-1 risk MDS who have relapsed after or are refractory to prior treatment with an ESA. IMerge is designed in two parts: Part 1 is a Phase 2, open-label, single-arm design and Part 2 is designed to be a Phase 3, randomized, controlled trial.

As previously announced, 32 patients were enrolled in Part 1 of IMerge, of which a subset of 13 patients had not received prior treatment with either a hypomethylating agent (HMA) or lenalidomide and did not have a del(5q) chromosomal abnormality. As of May 2017, the 13-patient subset showed an increased durability and rate of red blood cell (RBC) transfusion independence (TI) compared to the overall trial population (≥8-week RBC-TI: 53.8% vs 34.4%). Based on these data, Part 1 is being expanded to enroll approximately 20 additional patients who are non-del(5q) and naïve to HMA and lenalidomide treatment to increase the experience and confirm the benefit-risk profile of imetelstat in this refined target patient population. Janssen has opened the expanded Part 1 for patient enrollment. For more information about IMerge, please visit View Source

Results for the original 32 patients in Part 1 of IMerge, including hematologic improvement and rate of RBC-TI lasting at least 24 weeks, as well as duration of response and safety information, are expected to be presented at an upcoming major medical conference.

About Imetelstat

Imetelstat (GRN163L; JNJ-63935937) is a potent and specific inhibitor of telomerase that is administered by intravenous infusion. This first-in-class compound, discovered by Geron, is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Preliminary clinical data suggest imetelstat might have disease-modifying activity by inhibiting the progenitor cells of the malignant clones associated with hematologic malignancies in a relatively select manner. Most commonly reported adverse events in imetelstat clinical studies include fatigue, gastrointestinal symptoms and cytopenias. Imetelstat has not been approved for marketing by any regulatory authority.

About the Collaboration with Janssen

On November 13, 2014, Geron entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc., to develop and commercialize imetelstat for oncology, including hematologic myeloid malignancies, and all other human therapeutics uses. Under the terms of the agreement, Geron received an upfront payment of $35 million and is eligible to receive additional payments up to a potential total of $900 million for the achievement of development, regulatory and commercial milestones, as well as royalties on worldwide net sales. All regulatory, development, manufacturing and promotional activities related to imetelstat are being managed through a joint governance structure, with Janssen responsible for these activities.

On October 31, 2017 Minneapolis-based Humanetics Corporation (Humanetics) reported data at the annual meetings of the American Society for Radiation Oncology (ASTRO) and the Radiation Research Society (RRS) (Press release, Humanetics, OCT 31, 2017, View Source [SID1234521342]). The annual ASTRO meeting was held September 24th through the 27th in San Diego, California and the annual RRS meeting was held October 15th through the 18th in Cancun, Mexico. Dr. Zeljko Vujaskovic, M.D., Ph.D., a professor of radiation oncology at the University of Maryland School of Medicine (UMSOM) and director of the school’s Division of Translational Radiation Sciences, and Michael Kaytor, Ph.D., vice president of research and development at Humanetics, respectively, presented data related to Humanetics’s new drug candidate, BIO 300, which is being evaluated as a potential treatment to prevent erectile dysfunction in patients undergoing radiotherapy for prostate cancer.

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Prostate cancer is the most common non-skin cancer affecting men in the U.S. According to the National Cancer Institute (NCI), nearly 162,000 men will be diagnosed with prostate cancer in the U.S. in 2017, representing approximately 20% of all new cancers in men. While survival rates are high, radiation-induced erectile dysfunction (ED) is a common and lingering side effect associated with prostate radiotherapy. Nearly half of all men undergoing radiation treatment for prostate cancer will experience some level of ED.

Data presented included the results of nonclinical studies that were conducted at UMSOM. These studies demonstrated the potential of BIO 300 to both mitigate radiation-induced ED and also to improve the effectiveness of radiation therapy to kill tumors. “These compelling results show the promise of BIO 300 to enhance a prostate cancer patient’s quality of life, while also directly impacting the ability of radiation therapy to kill the tumor,” said Dr. Vujaskovic. “If this result can be translated to the clinical treatment of prostate cancer, it would represent a breakthrough in prostate cancer treatment outcomes.”

At present, there are no FDA-approved drugs to mitigate radiation-induced ED. “BIO 300’s potential to enhance radiation’s killing effect on the tumor while reducing treatment-related side effects is unparalleled,” said Dr. Kaytor. “These findings support the advancement of BIO 300 into a human efficacy study, which is anticipated to begin in 2018.”

BIO 300 is in development for prevention and mitigation of toxicities associated with radiation exposure for the treatment of multiple cancers and is currently in a Phase Ib/IIa clinical trial in patients with non-small cell lung cancer who are receiving chemoradiotherapy.

On October 31, 2017 Immunocore Limited, the world’s leading TCR company developing biological drugs to treat cancer, infectious diseases and autoimmune diseases, reported that overall survival data from two Phase I clinical trials of its wholly owned, lead programme, IMCgp100, in metastatic uveal melanoma will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 32nd Annual Meeting (Press release, Immunocore, OCT 31, 2017, View Source [SID1234521335]). This year’s SITC (Free SITC Whitepaper) is taking place 8 – 12 November, 2017, at the Gaylord National Resort & Convention Center in National Harbor, Maryland in USA.

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Poster Presentation Information:
Title: Safety, efficacy and biology of the gp100 TCR-based bispecific T cell redirector, IMCgp100 in advanced uveal melanoma in two Phase 1 trials
Authors: Richard Carvajal, Takami Sato, Alexander N. Shoushtari, Joseph Sacco, Paul Nathan, Marlana Orloff, Pippa Corrie, Neil Steven, Jeff Evans, Jeffrey Infante, Mario Sznol, Clive Mulatero, Omid Hamid, Leonel Hernandez-Aya, Nicola Little, Cheryl McAlpine, David Krige, Namir J. Hassan, Sanjay Patel, Ann-Marie Hulstine, Christina M. Coughlin, Mark R. Middleton
Category: Clinical Trials (Completed)
Date: Saturday 11 November 2017
Time: 12:30 – 14:00 & 18:30 – 20:00
Abstract Number: P208

The details of the clinical trial can be found on clinicaltrials.gov.

Furthermore, a poster presenting findings from a study mapping the treatment pathway for patients with metastatic uveal melanoma in England will be presented.

Title: Mapping the treatment pathway for metastatic uveal melanoma (mUM) patients in England: A qualitative pilot study
Authors: Elisabeth Adams, Chih-Yuan Cheng, Joseph Sacco, Sarah Danson, Pippa Corrie, Paul Nathan, Peter Szlosarek, Joanne Upton, Abolore Amuludun, Toby Toward
Category: Best Practices for Improving Cancer Immunotherapy Treatment Administration and Polypharmacy Management
Date: Friday 10 November 2017
Time: 12:30 – 14:00 & 18:30 – 20:00
Abstract: P437

To view the posters, please visit the SITC (Free SITC Whitepaper) website at View Source

SITC is the world’s leading member-driven organisation specifically dedicated to improving cancer patient outcomes by advancing the science and application of cancer immunotherapy.

On October 31, 2017 Hutchison China MediTech Limited (“Chi‑Med”) (AIM/Nasdaq: HCM) reported that it has initiated FRUTIGA, a pivotal Phase III clinical trial of fruquintinib in combination with paclitaxel (Taxol) for the treatment in advanced gastric or gastroesophageal junction (“GEJ”) adenocarcinoma patients in China (Press release, Hutchison China MediTech, OCT 31, 2017, http://www.chi-med.com/initiates-frutiga-phase-iii-trial/ [SID1234521334]). Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors (“VEGFR”) 1, 2 and 3. This randomized, double-blind, placebo-controlled, multicenter trial is being conducted in patients with advanced gastric cancer who have progressed after first-line standard chemotherapy. Advanced gastric cancer is a major medical need, particularly in Asian populations, with limited treatment options for patients who have failed first-line standard chemotherapy with 5-fluorouracil (5-FU) and platinum doublets. For gastric cancer, there are approximately 679,100 new cases and 498,000 deaths in China each year.[i]

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“Fruquintinib was designed to be a highly selective inhibitor of VEGFR 1, 2 and 3, which has shown the potential ability to combine with chemotherapy – a novel approach in the treatment of advanced gastric cancer,” said Christian Hogg, Chief Executive Officer of Chi-Med. “With fruquintinib’s New Drug Application (“NDA”) in third-line colorectal cancer (“CRC”) under review and its Phase III trial in third-line non-small cell lung cancer nearing full enrollment, we are excited to now also enter the final phase of development in second-line gastric cancer, a very large indication in which there is significant patient need for new treatment options in China.”

About FRUTIGA
Over 500 patients will be enrolled into FRUTIGA, a randomized, double-blind, Phase III trial to evaluate the efficacy and safety of fruquintinib combined with paclitaxel compared with paclitaxel monotherapy for second-line treatment of advanced gastric or GEJ adenocarcinoma. The trial will enroll patients with disease that has been confirmed through histology or cytology and who did not respond to first-line standard chemotherapy containing platinum and fluorouracil. All subjects will receive fruquintinib or placebo combined with paclitaxel. Patients will be randomized at a 1:1 ratio and stratified according to factors such as stomach vs. GEJ tumors and ECOG performance status. An Independent Data Monitoring Committee (IDMC) will be established to review safety and efficacy data.

The Primary efficacy endpoint is overall survival (“OS”). Secondary efficacy endpoints include progression-free survival (“PFS”, as defined by RECIST 1.1), objective response rate (“ORR”), disease control rate (“DCR”), duration of response, and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers related to the antitumor activity of fruquintinib will also be explored.

Additional details about this study can be found at clinicaltrials.gov, using identifier NCT03223376.

FRUTIGA was initiated following the results of an open label, multi-center Phase Ib dose finding/expansion study of fruquintinib in combination with paclitaxel (Taxol) in second-line patients with advanced gastric cancer (clinicaltrials.gov identifier NCT02415023). Results were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2017. A total of 32 patients were enrolled in the study and 28 of 32 patients were evaluable for efficacy, with an ORR rate of 36% and a DCR of 68%. At the fruquintinib recommended Phase II dose (“RP2D”), ≥16 week PFS rate was 50% and ≥7 month OS was 50%. Tolerability of the RP2D combination was as expected with common treatment related Grade ≥3 adverse events (AEs) being neutropenia (41%), leukopenia (28%), decreased hemoglobin (6%), and hand-foot syndrome (6%).

About Gastric Cancer
Every year, it is estimated that approximately one million new patients around the world are diagnosed with gastric cancer, according to Frost & Sullivan, and in 2015 China represented approximately 44% of all newly diagnosed gastric cancer cases worldwide. In 2015, there were an estimated 679,100 incidence gastric cancer cases and 498,000 mortality cases in China, according to the National Central Cancer Registry of China.

Gastric cancer is the third most lethal cancer worldwide. As it is often diagnosed at an advanced stage, prognosis is poor with a median OS of less than 12 months. Although targeted therapy is under development in China, chemotherapy remains the mainstay of treatment for gastric cancer patients and confers only a moderate survival advantage. Accordingly, we see a high medical need for new targeted treatment options.

About Fruquintinib
Fruquintinib (HMPL-013) is a highly selective small molecule drug candidate that has been shown to inhibit VEGFR 24 hours a day via an oral dose, with lower off-target toxicities compared to other targeted therapies. Its tolerability, along with its clean drug-drug interaction profile demonstrated to date, may enable rational combination with other cancer therapies such as in our ongoing clinical trials of fruquintinib in combination with chemotherapy and targeted therapy.

At an advanced stage, tumors secrete large amounts of VEGF, a protein ligand, to stimulate formation of excessive vasculature (angiogenesis) around the tumor to provide greater blood flow, oxygen, and nutrients to the tumor. VEGF and VEGFR play pivotal roles in tumor-related angiogenesis, and fruquintinib inhibits the VEGF/VEGFR pathway. This represents an important therapeutic strategy in blocking the development of new blood vessels essential for tumors to grow and invade.

Fruquintinib is currently under joint development in China by Chi-Med and its partner Eli Lilly and Company.

About Fruquintinib Development in Other Cancer Types
The China Food and Drug Administration (“CFDA”) acknowledged acceptance of the NDA for fruquintinib for the treatment of patients with advanced colorectal cancer in June 2017, and was subsequently awarded priority review status in view of its significant clinical value, according to the CFDA announcement in September 2017. The NDA is supported by data from the successful FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with CRC in China, which was highlighted in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 5, 2017 (clinicaltrials.gov identifier NCT02314819).

In addition to the FRUTIGA and FRESCO Phase III trials, fruquintinib is being studied in China in a Phase III pivotal trial in non-small cell lung cancer (“NSCLC”), known as FALUCA (clinicaltrials.gov identifier NCT02691299); and a Phase II study using fruquintinib combined with Iressa (gefitinib) in the first-line setting for patients with advanced or metastatic NSCLC (clinicaltrials.gov identifier NCT02976116). Other studies currently being planned include new studies in the United States (clinicaltrials.gov identifier NCT03251378), and certain exploratory studies in combination with other oncology agents.

On October 31, 2017 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" and "the Company"), a biopharmaceutical company focused on the development of new cancer therapies, reported the presentation of new data at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) which was held October 26 -30, 2017 at the Pennsylvania Convention Center in Philadelphia (Press release, DelMar Pharmaceuticals, OCT 31, 2017, View Source [SID1234521333]).

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DelMar presented a poster entitled "DNA Damaging Agent Dianhydrogalactitol (VAL-083) Targets Homologous Repair (HR) Pathway and Suggests Combination Therapy with topoisomerase inhibitors and PARP inhibitors." A copy of this presentation can be viewed on the Company’s website. The poster summarizes recent research conducted by DelMar in collaboration with the University of Texas MD Anderson Cancer Center and the Vancouver Prostate Center. In these studies, VAL-083 was shown to rapidly introduce irreversible DNA interstrand crosslinks leading to persistent DNA double-strand breaks and cancer cell death. Treatment with VAL-083 induced S/G2 phase cell cycle arrest in all cancer cells tested, including ovarian, prostate, lung and glioma cells.

These results suggest the potential for synergy with treatments that depend on a cancer cell to be in the S-phase for activity. Such agents include topoisomerase inhibitors, commonly used in the treatment of brain cancer and other solid tumors, and PARP inhibitors, commonly used in the treatment of ovarian cancer. In combination studies, VAL-083 combined with either topoisomerase inhibitors or PARP inhibitors demonstrated synergy or super-additivity against a range of cancer cells. Topoisomerase inhibitors tested in combination with VAL-083 included etoposide and camptothecin. PARP inhibitors tested in combination with VAL-083 included olaparib, talazoparib and veliparib.

"We have previously demonstrated that VAL-083 maintains activity against cancer cells resistant to the most commonly used chemotherapies," stated Dr. Dennis Brown, DelMar’s Chief Scientific Officer. "The data presented here expand the opportunity to leverage VAL-083’s unique mechanism in combination with agents such as PARP inhibitors and topoisomerase inhibitors that are widely used the treatment of multiple cancers."

"Resistance to treatment can occur when cancer cells, or even a small group of cancer cells within a tumor, contain molecular alterations rendering them insensitive to a particular drug," continued Dr. Brown. "In other cases, cancer cells may adapt to the drug while it is being administered, acquiring molecular changes that allow them to escape its effects. We are enthusiastic about our results to date with VAL-083 as a single agent, but these data suggest the potential to further improve patient outcomes by combining VAL-083 with other anti-cancer agents that work by a different molecular mechanism. PARP inhibitors have recently gained significant interest in the treatment of ovarian cancer and are now being explored in multiple cancers. Topoisomerase inhibitors have been established as important components in the treatment of lung, ovarian, prostate and central nervous system tumors, but their utility can be limited by side effects. A synergistic combination with VAL-083 offers the potential to improve outcomes while minimizing toxic side-effects. We look forward to exploring potential combination therapy regimens especially through possible collaborations with companies currently marketing these agents."

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class", DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institutes.

VAL-083 has been granted an orphan drug designation by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas.

DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance in vitro. Further details regarding these studies can be found at View Source