On May 15, 2019 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported that the U.S. Food and Drug Administration (FDA or Agency) has lifted the partial clinical hold on AIM2CERV, the company’s Phase 3 clinical trial of axalimogene filolisbac (AXAL) for the treatment of patients with high-risk locally advanced cervical cancer (Press release, Advaxis, MAY 15, 2019, View Source [SID1234536303]). In its letter, the FDA acknowledged that the company satisfactorily addressed all hold questions.

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As announced on January 23, 2019, the FDA placed a partial clinical hold on this study relating to the Agency’s requests for additional information pertaining to certain AXAL chemistry, manufacturing and controls (CMC) matters. The Agency did not cite any safety issues related to the trial and all enrolled patients continued to receive treatment, per the trial protocol. However, no new patients were permitted to enroll in AIM2CERV during this partial hold.

"The Advaxis team worked diligently to provide a comprehensive response back to the FDA’s requests for additional CMC information, and through constructive dialogue, we successfully resolved the partial clinical hold," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "Our AXAL product has demonstrated a manageable safety profile in the over 400 patients we have dosed to date, and we look forward to working with our clinical research organization to reopen enrollment at AIM2CERV sites. We remain focused on our mission of developing innovative therapies to address unmet needs and improving the lives of people with cancer."

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack. In a Phase 2 trial evaluating axalimogene filolisbac for the treatment of persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), the drug candidate showed a 12-month overall survival rate of 38% in 50 patients. This is a 52% improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors.

Axalimogene filolisbac has received Fast Track designation for adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. The immunotherapy has also received orphan drug designation in three clinical indications.

On May 15, 2019 Eli Lilly and Company (NYSE: LLY) reported that it will participate in the Bank of America Merrill Lynch 2019 Health Care Conference on Wednesday, May 15, 2019 (Press release, Eli Lilly, MAY 15, 2019, View Source [SID1234536333]). Enrique Conterno, senior vice president of Lilly and president of Lilly Diabetes and Lilly USA, will participate in a fireside chat at 9:20 a.m. PDT (12:20 p.m. EDT).

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A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s Investor website at View Source A replay of the presentation will be available on this same website for approximately 90 days.

On May 15, 2019 X4 Pharmaceuticals, Inc. (Nasdaq:XFOR), a clinical-stage biopharmaceutical company focused on the development of novel therapeutics for the treatment of rare diseases, and The Leukemia & Lymphoma Society (LLS) reported a collaboration to accelerate the development of X4’s lead product candidate, mavorixafor (X4P-001) for the treatment of Waldenström’s macroglobulinemia (WM), a rare form of non-Hodgkin lymphoma (Press release, X4 Pharmaceuticals, MAY 15, 2019, View Source [SID1234536349]).

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Mavorixafor was selected for LLS’s Therapy Acceleration Program (TAP), a strategic initiative where LLS builds business alliances and collaborations with biotechnology companies and academic researchers to speed the development of new therapies for blood cancers. Under the collaboration, X4 will conduct a multi-national Phase 1/2 clinical trial to evaluate the safety and assess the preliminary anti-tumor activity of mavorixafor in combination with ibrutinib in WM patients. The trial is planned to commence this year. Lee Greenberger, Ph.D., chief scientific officer of LLS, will also serve as a member of an advisory board to X4, providing important strategy and partnership guidance throughout the trial.

"LLS’s selection of mavorixafor for TAP collaboration and investment reinforces its potential as a novel therapy for Waldenström’s macroglobulinemia. Approximately 30 to 40 percent of WM patients have a CXCR4 mutation, and a number of these patients do not respond well to current therapies," said Paula Ragan, Ph.D., president and chief executive officer of X4 Pharmaceuticals. "We look forward to working closely with Dr. Greenberger and the LLS TAP team to gain valuable data and insights throughout the upcoming clinical trial as we work to bring a new therapeutic option to patients with this rare form of cancer."

Mavorixafor is a first-in-class, oral, small molecule allosteric antagonist of the chemokine receptor CXCR4 and is designed to address certain rare primary immunodeficiency diseases and certain cancers, including lymphomas, in which genetic mutations in CXCR4 create abnormal trafficking of white blood cells and play a role in disease process.

"Through TAP, LLS is committed to advancing the development of promising investigational therapies that we believe have potential to improve standards of care for patients, especially in disease areas with high unmet medical need, such as Waldenström’s macroglobulinemia," said Dr. Greenberger. "Mavorixafor has demonstrated early promise in other disease areas with CXCR4 mutations, including solid tumors, and its potential application among CXCR4-mutant WM patients makes it an excellent fit and an important asset within our program as we work with innovative companies like X4 to uncover and develop cutting-edge therapies for patients with blood cancers."

About Waldenström’s Macroglobulinemia
Waldenström’s macroglobulinemia (WM) is a rare form of non-Hodgkin lymphoma and B-cell lymphoproliferative disorder. According to the American Cancer Society, approximately three per one million people are diagnosed each year, including 1,400 new cases in the United States annually. Recent advancements in whole-genome sequencing have identified genetic mutations in the disease similar to WHIM syndrome, a rare congenital primary immunodeficiency characterized by warts, hypogammaglobulinemia, infection and myelokathexis. Approximately 30 to 40 percent of WM cases express mutations in the CXCR4 gene in the cancer cells. In WM, somatic mutations of CXCR4 are associated with active tumor cells and possible drug resistance, including resistance to anti-CD20 monoclonal antibodies and Burton tyrosine kinase (BTK) inhibitors, such as ibrutinib, the current standard of care. WM patients with this somatic mutation have a dramatically reduced median progression-free survival, or mPFS, of approximately two years, whereas patients without the mutation have a mPFS of well over five years.

About the Therapy Acceleration Program
The Leukemia & Lymphoma Society’s Therapy Acceleration Program (TAP) identifies and funds innovative projects related to therapies, supportive care or diagnostics that have the potential to change the standard of care for patients with blood cancer, especially in areas of high unmet medical need. TAP funding assists both clinical investigators and companies in gaining critical clinical proof of concept data that better enables them to obtain the resources they need or a partner to complete the testing, registration and marketing of new treatments, supportive care and diagnostics for leukemia, lymphoma and myeloma. TAP funding is different from the traditional grant at LLS. The TAP review process is separate from the grant process and LLS’s TAP staff play an active advisory role and closely monitor each approved project. To learn more about how TAP works, please click here.

On May 15, 2019 Bayer reported findings from new analyses and data for Vitrakvi (larotrectinib), which is approved for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic tropomyosin receptor kinase (NTRK) gene fusion without a known acquired resistance mutation that are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment (Press release, Bayer, MAY 15, 2019, View Source [SID1234536366]).5 This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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In the analysis of children with TRK fusion cancer, there was an ORR of 94% as per investigator assessment using RECIST 1.1, with median DOR not reached at the time of data cut-off of July 30, 2018. In the analysis of adult patients with TRK fusion cancer, a response rate of 68% as per independent assessment and 76% as per investigator assessment was seen using RECIST 1.1, and with median follow up of 17.5 and 17.2 months, respectively, the median DOR had not been reached at time of data cut-off (July 30, 2018). New data on patients with primary central nervous system (CNS) tumors of various histologies or brain metastases will be presented as part of an oral presentation. An analysis on quality of life (QoL) with Vitrakvi treatment was also conducted in both children and adults with TRK fusion cancer. Adverse events seen with the new data for adults and children were mostly grade 1-2.1,2,3,4 The full data from these analyses will be presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2019, taking place in Chicago, Illinois from May 31 – June 4, 2019.

"These data further confirm the efficacy and safety of larotrectinib in patients with TRK fusion cancer, regardless of tumor type and age, including those who present with brain metastases or primary CNS tumors," said Douglas S. Hawkins, M.D., hematology/oncology division chief at Seattle Children’s Hospital and professor of pediatrics at the University of Washington School of Medicine. "It underscores the urgency for widespread genomic testing to identify patients."

"These latest data add to the body of evidence for larotrectinib in patients with TRK fusion cancer," said Scott Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer’s Pharmaceutical Division. "With our commitment to developing treatments like larotrectinib as well as the investigational TRK inhibitor BAY 2731954, we are demonstrating our commitment to researching and advancing the future of cancer care, while providing true value for patients and physicians."

Vitrakvi Presentations and Posters

Data from pediatric patients from the expanded dataset show an ORR of 94% (n=32/34) with Vitrakvi as per investigator assessment using RECIST 1.1, including 12 complete responses (CR), 18 confirmed partial responses (PR) and 2 PR pending confirmation.1 At the time of data cut-off (July 30, 2018), the median DOR had not been reached (range 1.6+ to 26.7+ months). (Oral Presentation 10010, Session: Pediatric Oncology II; Sunday, June 2, 8:12AM – 8:24AM (CDT), Room: S504)

Data in adult patients from the expanded dataset show an ORR of 68% as per independent assessment (n=44/65), including a 17% CR and 51% PR, and 76% by investigator assessment (n=56/74) with a 9% CR, 57% confirmed PR, and 9% PR pending confirmation.2 At the time of data cut-off (July 30, 2018), the median DOR had not been reached. (Poster Presentation 3122, Session: Developmental Therapeutics and Tumor Biology (Nonimmuno); Saturday, June 1, 8:00AM – 11:00AM (CDT), Room: Hall A)

An analysis across clinical trials of TRK fusion cancer patients with evaluable brain metastases (n=5) shows an ORR of 60% per investigator assessment using RECIST 1.1.3 Additional data will be provided in an oral presentation at ASCO (Free ASCO Whitepaper) on June 3, 2019. (Oral Presentation 2006, Session: Central Nervous System Tumors; Monday, June 3, 3:15PM – 3:27PM (CDT), Room: S102)

An evaluation on patient-reported outcomes is also being presented.4 (Poster Presentation 6602, Session: Health Services Research, Clinical Informatics, and Quality of Care; Saturday, June 1, 1:15PM – 4:15PM (CDT), Room: Hall A)

About Vitrakvi (larotrectinib)
Vitrakvi is indicated for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation that are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.5 This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Research suggests that the NTRK gene can become abnormally fused to other genes, producing a TRK fusion protein that can act as an oncogenic driver, promoting cell growth and survival in tumor cell lines.5

Important Safety Information for VITRAKVI (larotrectinib)

Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurologic adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).5

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.5

Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of patients.5

Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.5

Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily.5

Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.5

Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).5

Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.5

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.5

Please see the full Prescribing Information for VITRAKVI (larotrectinib).

About TRK Fusion Cancer
TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein.5 The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade.5 These TRK fusion proteins act as oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer, regardless to where it originates in the body.5 TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body.5 TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).5,6

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes five marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On May 15, 2019 AnHeart Therapeutics (Hangzhou) Co., Ltd.. (hereinafter referred to as AnHeart) reported the completion of the series A round of financing raising about 100 million Chinese yuan (Press release, AnHeart Therapeutics, MAY 15, 2019, View Source [SID1234555758]). The financing was exclusively provided by Decheng Capital, an internationally known venture capital institution specializing in the biomedical industry. This round of financing will be used to establish the AnHeart team to carry out Phase 2 clinical trials of its leading asset AB-106 and to further enrich the company’s product pipeline.

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AnHeart is a clinical stage company, specialized in acquisition, development and commercializing innovative drugs that improve human health and quality of life. Its leading asset is AB-106, an oral, highly selective ROS1/NTRK small molecule inhibitor. This new anticancer drug was acquired from Japan’s Daiichi Sankyo Co., Ltd. in December 2018.

Early clinical trials have shown that AB-106 had satisfactory safety and efficacy and exhibits long progression-free survival in patients with non-small cell lung cancer with ROS1 fusion mutations. Currently, AB-106 has completed phase 1 clinical trials in the United States and Japan for the treatment of patients with solid tumors and neuroendocrine tumors containing ROS1 or NTRK fusion genes. The latest Phase 1 clinical trial results are expected to be reported in detail at the China Clinical Oncology Association Annual Meeting (CSCO) in September 2019.

"AnHeart is committed to the development of innovative drugs with unmet clinical needs," said Dr. Wang Yuyuan, co-founder and CEO of AnHeart. "With the strong support from Decheng Capital, we successfully acquired worldwide global rights for AB-106 from Japan Daiichi Sankyo and took over the long-term follow-up of the product in the US IND and Phase 1 clinical trials." Strategic collaborations are one of the strategies of Anheart. The company plans to establish and enhance clinically innovative product pipelines with near key value inflection points by working with large and medium-sized biopharmaceutical companies."

Dr. Yan Bing, Co-Founder and CMO of Anheart added: "Our team has very rich clinical development experience, and successful drug approval experience in Asia Pacific, Europe and America. We also have long term collaboration with top industry leaders as well. In fact, leveraging our global clinical development capabilities and interdisciplinary expert networks to optimize the clinical commercial value of assets is another strategy of AnHeart."

"Besides acquiring clinical assets by cooperation with large and medium-sized biopharmaceutical projects, we also consider introducing and developing assets that have not entered the clinical phase but have demonstrated good potential in animal experiments in order to build and consolidate an innovative product pipeline", Dr. Zheng Lihua, Co-Founder and CBO of AnHeart added.

"We are very glad we have the opportunity to support Anheart", said Dr. Cui Xiangmin, Managing Partner of Decheng Capital. "AnHeart has built a very successful clinical development team. We believe that AnHeart can use its strength in clinical development to bring a variety of innovative drugs to the market to meet the clinical needs of patients."