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Servier and Taiho Oncology Present Latest LONSURF® (trifluridine/tipiracil) Data at ASCO 2019 Gastrointestinal Cancers Symposium (ASCO GI)

On January 17, 2019 Servier and Taiho Oncology, Inc. (U.S.), a subsidiary of Taiho Pharmaceutical Co., Ltd. (Japan), jointly reported that the safety and efficacy data in the gastrectomy patient subgroup of the global Phase III trial TAGS evaluating LONSURF (trifluridine/tipiracil, TAS-102) in patients with metastatic gastric cancer (mGC) are consistent with the overall study results published in The Lancet Oncology (Press release, Servier, JAN 17, 2019, View Source [SID1234532712]). These data were highlighted in an oral presentation at the ASCO (Free ASCO Whitepaper) 2019 Gastrointestinal Cancers Symposium (ASCO-GI) on Thursday 17 January.

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In TAGS, 221 (44%) of the 507 randomized mGC patients had undergone prior gastrectomy (147 LONSURF, 74 placebo), which is reflective of the real-world patient population diagnosed with mGC. The results confirmed that trifluridine/tipiracil prolonged survival versus placebo regardless of prior gastrectomy. The overall results of TAGS demonstrated that patients treated with oral trifluridine/tipiracil showed a clinically meaningful and statistically significant improvement in overall survival (OS) compared with placebo and a 31 percent risk reduction of death (HR 0.69 one sided p=0.00029), which translated into a prolonged median survival of 2.1 months (5.7 months for trifluridine/tipiracil versus 3.6 months for placebo).

Additional data investigating trifluridine/tipiracil in metastatic colorectal cancer (mCRC) patients will be presented during a poster session on Saturday 19 January:

Health-related quality of life in the early-access phase IIIb study of trifluridine/tipiracil in pretreated metastatic colorectal cancer (mCRC): Results from PRECONNECT study (abstract 638)
Validation of cost-effectiveness of trifluridine/tipiracil versus best supportive care and regorafenib for previously treated metastatic colorectal cancer in the UK using phase IIIb PRECONNECT early access clinical trial data in the real world setting (abstract 639)
QoL from TASCO1: Health related quality of life of trifluridine/tipiracil-bevacizumab and capecitabine-bevacizumab as first-line treatments in metastatic colorectal cancer patients not eligible for intensive chemotherapy: results from the TASCO1 phase II study (abstract 676)
Trifluridine/tipiracil and regorafenib in patients with metastatic colorectal cancer (mCRC): A single institution retrospective study (abstract 592)
Exploratory analysis of the effect of trifluridine/tipiracil in patients treated in RECOURSE by prognostic factors (abstract 677)
Trifluridine/tipiracil is indicated in European Union for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan- based chemotherapies, anti-VEGF agents, and anti-EGFR agents.1 Applications for an additional indication in mGC for LONSURF are currently under review by health authorities in Japan, the United States and the European Union.

About TAGS

TAGS (TAS-102 Gastric Study) is a Taiho-sponsored pivotal Phase III, multinational, randomized, double-blind study evaluating trifluridine/tipiracil, also known as TAS-102, plus best supportive care (BSC) versus placebo plus BSC in patients with metastatic gastric cancer, including gastroesophageal junction cancer, refractory to standard treatments. The primary endpoint in the TAGS trial is OS, and the main secondary endpoint measures include progression-free survival (PFS), and safety and tolerability, as well as quality of life.

TAGS enrolled 507 adult patients with metastatic gastric cancer who had previously received at least two prior regimens for advanced disease. The study was conducted in Belarus, the European Union, Israel, Japan, Russia, Turkey and the United States.

For more information on TAGS, please visit www.ClinicalTrials.gov (View Source). The ClinicalTrials.gov Identifier is NCT02500043.

About Metastatic Gastric Cancer

Gastric cancer, also known as stomach cancer, is a disease in which malignant cells form in the lining of the stomach. It is the fifth most common cancer worldwide and the third most common cause of cancer-related death (after lung and liver cancer), with an estimated 723,000 deaths annually.2　

When cancer spreads it is called advanced cancer. Locally advanced cancer is when the cancer has grown outside the organ it started in but hasn’t spread to other parts of the body. When the cancer spreads to other parts of the body, this is called metastatic cancer. In the last two decades, the proportion of patients with gastric cancer who present with metastases has risen to over 40%.3

Standard chemotherapy regimens for advanced gastric cancer include fluoropyrimidines, platinum derivatives, and taxanes (with ramucirumab), or irinotecan. The addition of trastuzumab to chemotherapy is standard of care for patients with HER2-neu-positive advanced gastric cancer. However, after failure of first- and second-line therapies, standard third-line treatments are limited.

About Metastatic Colorectal Cancer

Colorectal cancer is the third most common cancer worldwide with approximately 1.4 million new diagnoses in 2012.4 Each year there are over 690,000 deaths making it the fourth biggest cancer killer worldwide (after lung, liver and gastric cancer).5 Those with metastatic disease (where the cancer has spread from the primary site) the average five-year survival is approximately 11%.6 Standard chemotherapy regimens for advanced metastatic colorectal cancer include fluoropyrimidines, oxaliplatin, irinotecan or targeted treatments, such as those that target vascular endothelial growth factors (VEGF) or endothelial growth factor receptors (EGFR).

Over the last decade, clinical outcomes for patients with mCRC have improved considerably due to the advent of novel treatment agents, predictive biomarkers, and a more strategic approach to the delivery of systemic therapies. Currently, the median overall survival for patients with mCRC being treated both in phase III trials and in large observational series or registries is 30 months – more than double that of 20 years ago.7,8,9

About LONSURF

LONSURF (trifluridine/tipiracil) is an oral anticancer drug, which utilizes the combination of trifluridine (FTD) and tipiracil (TPI), whose dual mechanism of action is designed to maintain clinical activity and differs from conventional fluoropyrimidines. Trifluridine is an antineoplastic nucleoside analogue, which is incorporated directly into the DNA, thereby interfering with the function of DNA. The blood concentration of trifluridine is maintained via tipiracil, which is an inhibitor of the trifluridine-degrading enzyme, thymidine phosphorylase.

In Japan, Taiho Pharmaceutical Co., Ltd. has been marketing LONSURF for the treatment of unresectable advanced or recurrent colorectal cancer since 2014. In the United States, beginning in 2015, Taiho Oncology, Inc., a U.S. subsidiary of Taiho Pharmaceutical, began marketing the drug for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In June 2015, Taiho Pharmaceutical and Servier entered into an exclusive license agreement for the co-development and commercialization of LONSURF in Europe and other countries outside of the United States, Canada, Mexico and Asia. In parts of Asia outside of Japan, Taiho Pharmaceutical’s business partner TTY Biopharm launched LONSURF in Taiwan in July 2018, and Jeil Pharmaceutical is preparing to bring the drug to market in South Korea.

As of December 2018, LONSURF has been approved as a treatment for advanced mCRC in 62 countries and regions worldwide.

Adaptive Biotechnologies Announces Medicare Coverage of the clonoSEQ® Assay for MRD Testing in Patients with Multiple Myeloma and Acute Lymphoblastic Leukemia at Multiple Timepoints Throughout Treatment and Remission

On January 17, 2019 Adaptive Biotechnologies, an immune driven-medicine company, reported that Palmetto GBA, a Medicare Administrative Contractor (MAC) and leader in assessing diagnostic technologies through its MolDX program, has established coverage of the clonoSEQ Assay for Medicare patients with multiple myeloma and B-cell acute lymphoblastic leukemia (ALL) (Press release, Adaptive Biotechnologies, JAN 17, 2019, View Source [SID1234532711]). clonoSEQ is the first and only test authorized by the U.S. Food and Drug Administration (FDA) to detect and monitor minimal residual disease (MRD) in myeloma and ALL using DNA from a patient’s bone marrow sample. The Medicare coverage for clonoSEQ is aligned with the assay’s FDA label and with clinical practice guidelines in myeloma and ALL and includes assessing MRD at multiple time points throughout therapy to monitor treatment response and help predict patient outcomes. The article, also posted by the MAC Noridian, is effective immediately and enables national coverage of Medicare patients undergoing clonoSEQ testing.

"Availability of sensitive, specific and standardized MRD testing is increasingly crucial to the delivery of optimal patient care in both multiple myeloma and ALL," said Nikhil Munshi, M.D., Director of Basic and Correlative Science at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. "Medicare coverage for the clonoSEQ Assay will help ensure that eligible patients across the U.S. have access to a highly advanced option for MRD assessment to support more personalized treatment decisions across their course of care."

MRD refers to the remaining number of cancer cells that are present in a patient’s body during and after treatment and may eventually lead to recurrence of the disease. Cancer treatment guidelines for myeloma and ALL call for MRD testing to assess disease burden throughout the course of care to help monitor for remission, detect relapse, determine response to treatment and predict patient outcomes. Controlled trials have shown that even the smallest amounts of residual disease significantly predict a patient’s long-term clinical outcomes.

"This is great news for patients. The establishment of favorable Medicare coverage for clonoSEQ soon after FDA authorization further demonstrates the clinical relevance of MRD assessment and underscores the benefit that this test delivers in the management of myeloma and ALL patients," said Charles Sang, senior vice president, Adaptive Diagnostics. "clonoSEQ is a highly sensitive and standardized MRD test that enables more cost-effective care by assessing the effectiveness of therapy, monitoring remission and identifying relapse in lymphoid blood cancers, serving as a critical tool to help clinicians decide if a patient should initiate, pause or discontinue a potentially costly treatment regimen."

clonoSEQ testing has been used in 25 of the 28 of the National Comprehensive Cancer Network (NCCN) centers in the U.S., and Adaptive is working diligently with community practice leaders to increase use in the community setting. As MRD assessment becomes standard practice for patient management across a range of blood cancers, it is essential that clinicians and patients have access to a highly accurate, sensitive and standardized MRD assessment tool. Having satisfied the analytical and clinical validation requirements of the FDA and met the bar for clinical utility required by Medicare, the clonoSEQ Assay addresses this need.

Adaptive continues to work closely with third-party payers to obtain coverage of clonoSEQ for eligible patients in need. With Medicare coverage in place, Adaptive is strongly positioned to expand commercialization of clonoSEQ in 2019. The company is committed to pursuing regulatory approval for additional potential indications for clonoSEQ in other blood cancers and sample types, including blood-based MRD assessment.

The clonoSEQ coverage decision can be found here.

About the clonoSEQ Assay

The Adaptive Biotechnologies clonoSEQ Assay has been granted De Novo designation by the FDA as an in vitro diagnostic (IVD) to detect and monitor minimal residual disease (MRD) in patients with multiple myeloma (MM) and B-cell acute lymphoblastic leukemia (ALL) using DNA from bone marrow samples. It identifies and quantifies specific DNA sequences found in malignant cells, allowing clinicians to monitor patients for changes in disease burden during and after treatment. This robust assay provides sensitive and accurate measurement of residual disease that allows physicians to predict patient outcomes, assess response to therapy over time, monitor patients during remission and detect potential relapse. The clonoSEQ Assay is a single-site assay performed at Adaptive Biotechnologies. It is also available as a CLIA-regulated laboratory developed test (LDT) service for use in other lymphoid cancers.

clonoSEQ was reviewed under the FDA’s De Novo premarket review pathway, a regulatory pathway for some low- to moderate-risk novel devices for which there is no legally marketed predicate device.

For important information about the FDA-cleared uses of clonoSEQ, including the full intended use, limitations, and detailed performance characteristics, please visit www.clonoSEQ.com/technical-summary

Zymeworks Reports Second Investigational New Drug (IND)-Submission Milestone Achieved in Lilly Collaboration

On January 17, 2019 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported the achievement of a new development milestone in its collaboration with Eli Lilly and Company ("Lilly") (Press release, Zymeworks, JAN 17, 2019, View Source;Submission [SID1234532710]). In accordance with Zymeworks’ 2014 licensing and collaboration agreement with Lilly, Zymeworks will receive a milestone payment of US$8.0 million for Lilly’s submission of an IND application for an immuno-oncology bispecific antibody enabled by Zymeworks’ proprietary Azymetric platform.

"We believe that Lilly’s submission of a second IND on an Azymetric bispecific drug candidate within a six-month period is further evidence that Zymeworks’ platform technologies are enabling our global pharmaceutical partners to accelerate drug development into the clinic," said Ali Tehrani, Ph.D., President and Chief Executive Officer of Zymeworks. "As one of our first collaborators, Lilly’s successes demonstrate the ease of use, productivity and promise of our proprietary platforms, especially for advancing therapeutic programs into the clinical setting."

Under its two licensing and collaboration agreements with Lilly, Zymeworks has granted Lilly worldwide licenses to research, develop, and commercialize multiple bispecific therapeutics directed towards Lilly’s targets. To date, Zymeworks has received multiple equity investments, an upfront licensing payment and multiple research and development milestone payments under these agreements. Zymeworks is also eligible to receive further development and commercial milestone payments and tiered royalties on global product sales.

About the Azymetric Platform

The Azymetric platform enables the transformation of monospecific antibodies into bispecific antibodies, giving the antibodies the ability to simultaneously bind two different targets. This unique technology enables the development of multifunctional biotherapeutics that can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering degradation, and increase tumor-specific targeting. These features are intended to enhance efficacy while reducing toxicities and the potential for drug resistance. Azymetric bispecifics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life and high stability. In addition, they are compatible with standard manufacturing processes with high yields and purity, potentially significantly reducing drug development costs and timelines.

Five Prime Therapeutics Presents Data from Safety Lead-in to Phase 3 FIGHT Trial of Bemarituzumab at 2019 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium

On January 17, 2019 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that a poster entitled "Phase 1 Results from the Phase 1/3 FIGHT Study Evaluating Bemarituzumab and mFOLFOX6 in Advanced Gastric/GEJ Cancer" was presented today at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancer Symposium in San Francisco (Press release, Five Prime Therapeutics, JAN 17, 2019, View Source [SID1234532709]). The poster (Board J1, Abstract #91) can be found online at Five Prime Therapeutics Scientific Publications.

"Gastric cancer with FGFR2b overexpression or FGFR2 gene amplification is associated with a poor prognosis for patients with advanced disease," said Helen Collins, M.D., senior vice president and chief medical officer of Five Prime. "We completed the Phase 1 safety lead-in and saw no dose-limiting toxicities with the combination of bemarituzumab and mFOLFOX6. Additionally, we are encouraged to see evidence of clinical activity with the combination. The FIGHT Phase 3 study is currently enrolling patients worldwide with newly diagnosed advanced gastric and gastroesophageal junction cancer whose tumors overexpress FGFR2b with the goal of providing a better first-line treatment option for these patients."

The Phase 1 portion of the study achieved the primary objective of determining a recommended dose of bemarituzumab in combination with mFOLFOX6 to initiate the Phase 3 portion of the FIGHT trial. Key inclusion criteria for the Phase 1 patient population included: adults with incurable GI cancer for whom mFOLFOX6 was an appropriate therapy, an ECOG score of 0-1, and evaluable disease by RECIST v1.1. The patient population was not selected for FGFR2b status or limited to patients without prior chemotherapy treatment for advanced or metastatic disease. At the time of publication, 2 patients with gastric/esophageal cancer were confirmed to be FGFR2 positive with 1 achieving a PR and the other demonstrating a complete metabolic response.

FIGHT Trial

In December 2017, Five Prime initiated the Phase 1 portion (NCT03343301) of the Phase 1/3 FIGHT (FGFR2b Inhibition in Gastric and Gastroesophageal Junction Cancer Treatment) global registrational trial. The Phase 1 safety lead-in portion of the trial was designed to identify a recommended dose of bemarituzumab in combination with the modified FOLFOX6 standard-of-care chemotherapy regimen (mFOLFOX6) to support the initiation of the Phase 3 portion of the trial.

The Phase 3 portion of the FIGHT trial will evaluate bemarituzumab in combination with mFOLFOX6 versus placebo plus mFOLFOX6 in approximately 550 patients with gastric cancer (GC) or gastroesophageal junction (GEJ) cancer whose tumors overexpress FGFR2b. The Phase 3 portion of the trial began in September 2018 and will include more than 250 sites in the U.S., Europe and Asia.

The primary endpoint of the FIGHT trial is overall survival (OS) with secondary endpoints of progression-free survival (PFS), objective response rate (ORR), safety and pharmacokinetic (PK) parameters.

Previous Bemarituzumab Trial Results

Data from a Phase 1 clinical trial of single-agent bemarituzumab were presented at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting. Bemarituzumab demonstrated single-agent activity and an acceptable safety profile in heavily pretreated patients with metastatic gastric cancer whose tumors overexpress FGFR2b.

Efficacy:

In 21 treated patients with late-line GC/GEJ and high FGFR2b overexpression:
ORR was 19.0% with 4 confirmed PRs
Disease control rate at 6 weeks: 57.1%
Median duration of response was 15.4 weeks
Safety:

Bemarituzumab was well tolerated
There were no dose-limiting toxicities
Maximum tolerated dose was not reached during dose escalation
Unmet Need in GC and GEJ

GC, including GEJ cancer, is the fifth most common cancer worldwide and third leading cause of cancer death. The presence of FGFR2 gene amplification or FGFR2b overexpression is associated with a worse prognosis and is present in 10% of patients with GC/GEJ.

Current first-line chemotherapy treatments prolong survival by approximately 6 months compared to best supportive care, but median OS remains poor with literature-reported ranges of approximately 10 to 11 months and PFS from 5 to 5.6 months. An unmet medical need exists in the treatment for GC/GEJ since few treatment options following progression are available after first-line chemotherapy.

Companion Diagnostic Development for FGFR2b

Five Prime is using companion diagnostics to identify FGFR2b overexpression using an IHC test and FGFR2 gene amplification using ctDNA analysis. Five Prime will use both assays to select patients for the FIGHT trial to identify the estimated 10% of patients with gastric and GEJ tumors that would qualify for the trial.

About Bemarituzumab

Bemarituzumab is a first-in-class, isoform-selective, humanized monoclonal antibody in clinical development as a targeted immunotherapy for tumors that overexpress FGFR2b, a splice variant of a receptor for some members of the fibroblast growth factor (FGF) family. Bemarituzumab has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) to increase direct tumor cell killing by recruiting natural killer (NK) cells. Clinical results to date suggest that the specificity of bemarituzumab avoids the dose-limiting toxicities that have been seen with less selective pan-FGFR tyrosine kinase inhibitors that act on multiple FGFRs, including FGFR2.

Physicians’ Education Resource® to Host 15th Annual International Symposium on Melanoma and Other Cutaneous Malignancies®

On January 17, 2019 Physicians’ Education Resource (PER), a leading resource for continuing medical education (CME), reported that it will host its 15th annual International Symposium on Melanoma and Other Cutaneous Malignancies Saturday, Feb. 9, at the InterContinental New York Times Square in New York City. This educational conference will be co-chaired by Omid Hamid, M.D., chief of translational research and immunotherapy and director of melanoma therapeutics at The Angeles Clinic and Research Institute and Jeffrey S. Weber, M.D., Ph.D., deputy director of the Perlmutter Cancer Center at New York University Langone Health.

"We are looking forward to hosting our International Symposium on Melanoma and Other Cutaneous Malignancies once again in New York City," said Phil Talamo, president of PER. "Now in its 15th year, the symposium continues to provide physicians with the tools they need to personalize care for every patient they treat with skin and other cutaneous including some very exciting data in the adjuvant setting."

Throughout the international conference, world-renowned melanoma experts Hamid and Weber, along with distinguished skin cancer specialists, will host several sessions covering topics such as current advances in immunotherapy and targeted therapies, the benefits of regional therapy, how to use predictive and prognostic modeling and how to manage treatment-related adverse events associated with emerging strategies. This symposium will also feature a Medical Crossfire, in which the expert panel will address attendees’ questions and participate in a rigorous debate on pressing issues faced by the skin cancer treatment community.

This highly interactive symposium will also feature a special presentation, "We Are What We Eat: How the Microbiome Influences Responses to Immunotherapy in Cancer," by Thomas F. Gajewski, M.D., Ph.D., AbbVie Foundation professor of cancer immunotherapy at University of Chicago Medicine. Gajewski investigates and develops new treatments for patients with melanoma. He also serves as an editor for Cancer Research and the Journal for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).

The 15th annual International Symposium on Melanoma and Other Cutaneous Malignancies is a one-day conference, revolutionizing the presentation of emerging therapies and evolving standards of care in the management of patients with melanoma and other skin cancers. Attendees who attend this educational conference will gain insight on the latest strategies for the use of checkpoint inhibitors, current and emerging treatments for the BRAF gene as it affects mutant melanoma, and mitigating treatment-related toxicities with targeted therapy and immunotherapies.