On February 7, 2020 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has entered into an agreement with National Cancer Center Japan to support an investigator-initiated clinical study based on the patient-requested therapy system (Press release, Chugai, FEB 7, 2020, View Source [SID1234554000]).

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The clinical research program titled "the prospective trial of patient-proposed healthcare services with multiple targeted agent based on the result of gene profiling by multigene panel test" is led by National Cancer Center Hospital as a coordinating secretariat. The study aims to examine new therapeutic opportunities for patients with genetic alterations identified with comprehensive genomic profiling tests who have no treatment options available including approved drugs or clinical trials by utilizing the patient-requested therapy system. Advocating the objectives of the clinical study, Chugai will provide drugs in the study.

"The recent insurance coverage for the genomic analysis using next-generation sequencing (NGS) technology enabled allow us to select optimized cancer treatment for each patient. However, some patients cannot receive molecularly matched therapy due to lack of approved drugs even if gene alteration has been identified. We are very pleased that our products will help offer such patients therapeutic opportunities," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "Chugai will continue striving to promote advanced personalized healthcare to realize the optimal treatment for each patient as a leading company in oncology."

On February 7, 2020 Elios Therapeutics, a biopharmaceutical company developing innovative personalized therapeutic cancer vaccines, reported that the Company presented a subgroup analysis of the prospective, randomized, double-blind, placebo-controlled Phase IIb clinical trial evaluating its personalized tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine, in patients with Stage III and IV resected melanoma (Press release, Elios Therapeutics, FEB 7, 2020, View Source [SID1234554058]).

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In the study, 144 participants were randomized to receive either the vaccine or placebo to prevent recurrence. The vaccines were initiated within three months of completion of standard of care therapy at 0, 1, 2, 6, 12, and 18 months. The protocol was amended to allow concurrent treatment with checkpoint inhibitors once approved for the adjuvant setting. The primary endpoint was 24-month disease-free survival (DFS). This pre-specified sub-group analysis examined efficacy by stage, immunotherapy, and checkpoint inhibition. The analysis was performed on the intent-to-treat (ITT) population and per treatment (PT) population, which included all patients who completed the primary TLPLDC or placebo vaccine series at six months.

In the PT analysis, 24-month DFS improved among Stage IV patients in the TLPLDC vaccine group compared to placebo (73.0% vs. 0%; p=0.002) representing a statistically significant and clinically meaningful reduction in the relative risk of disease recurrence for these patients. An improvement was also seen in the ITT analysis (43.0% vs. 0%; p=0.098). Stage IV patients were more likely to receive checkpoint inhibitor therapy (50% vs. 26%, p=0.003). At the 24-month assessment, a difference in DFS between the vaccine and placebo arms was not observed in Stage III patients. Patients with Stage III disease often take longer to experience a recurrence than patients with Stage IV disease, therefore a 36-month assessment of DFS will determine the effect of treatment in this population.

Additionally, while not statistically significant due to the sample size, a clinically meaningful improvement in 24-month DFS was observed between patients receiving the vaccine in combination with standard-of-care checkpoint inhibitors versus checkpoint inhibitors alone.

"Patients with Stage III and IV melanoma who have completed initial treatment have a very high risk of having their disease return, representing a serious unmet medical need," said Mark B. Faries, M.D., co-director of the Melanoma Program and head of Surgical Oncology at The Angeles Clinic and Research Institute, an affiliate of Cedars-Sinai and principal investigator of the study. "Achieving a 73 percent disease-free survival rate in this extremely challenging stage of disease is significant. Importantly, in this study we see that checkpoint inhibitors, when combined with a cell-based vaccine like TLPLDC, may produce a synergistic anti-tumor response. The goal of this type of approach is to increase patient responses and prevent disease recurrence."

As previously reported, treatment with the TLPLDC vaccine was well-tolerated with 31.7 percent of placebo patients and 35.9 percent of TLPLDC patients experiencing a related adverse event, the majority of which were grade 1 or 2. The study will continue as designed to achieve the 36-month landmark secondary endpoints of DFS and overall survival (OS), which are anticipated in June 2020.

"Based on the encouraging data from this study, and recent End-of-Phase II discussions with the FDA, we are planning for a registration-enabling study of the TLPLDC vaccine in this high unmet need population of patients with Stage III and IV melanoma," said Buddy Long, chief executive officer of Elios Therapeutics. "We continue to focus on our mission to bring this safe and effective treatment to patients with melanoma as soon as possible."

The TLPLDC vaccine is a personalized treatment that is created using a patient’s own blood and tumor cells. Samples are collected at resection, frozen, and sent to the lab where they are used to create autologous tumor lysate, which is loaded into yeast cell wall particles (YCWP). This combination is then introduced to the patient’s dendritic cells, leading to the creation of the final TLPLDC vaccine. The time from resection to injection of the vaccine takes approximately three weeks.

Melanoma is more likely to grow and spread than other types of skin cancer. When diagnosed and treated at an early stage, melanoma has a high cure rate, however patients with later stages of the disease carry a high risk for melanoma recurrence because some melanoma cells can remain in the body, even after surgery. In the U.S, the incidence of melanoma has increased over the past decades, with 91,270 estimated new cases and 9,320 related deaths in 2018.1

Presentation Details:

Poster C10 (Abstract #63) – Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: a subgroup analysis. Friday, February 7, 2020 – Poster Session B at 11:30 AM – 1:00 PM EST and 6:00 PM – 7:00 PM EST
The poster can be accessed here.

About the Phase IIb TLPLDC Study
This Phase IIb study is a prospective, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of the TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine in patients with resected Stage III and IV melanoma. The primary endpoint of the trial is two-year disease-free survival (DFS).

In the study, 144 participants were randomized to receive either the vaccine or placebo to prevent recurrence. TLPLDC or placebo vaccines were initiated within three months of completion of standard of care (SoC) therapies and were given at 0, 1, 2, 6, 12, and 18 months. The protocol was amended to allow concurrent checkpoint inhibitor therapy once approved for the adjuvant setting. Study participants were followed for recurrence per SoC. The primary efficacy analysis was performed on the intent-to-treat (ITT) and the per treatment (PT) populations as co-primary analyses given the high early recurrence rate often seen in patients with advanced melanoma. Secondary endpoints include 36-month DFS and overall survival (OS) which will be compared between the vaccinated and control groups.

About TLPLDC
The TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine is a unique type of immunotherapy, both in how it is made and how it is delivered. The vaccine is personalized, meaning it is made from a patient’s tumor and blood. Every patient’s tumor has a unique antigenic profile unlike any other, and dendritic cells found in the blood are the most potent antigen-presenting cells in the body. Once TLPLDC is administered, it delivers the patient’s complete repertoire of tumor antigens to the immune system, creating a dual innate and adaptive immune response, activating fighter T cells, and triggering the immune system to recognize, and seek out and destroy any cells containing the antigens and specific mutations from their tumor.

Historically, autologous cancer vaccines have been rather onerous to develop, sometimes taking months between the tumor biopsy and administration. Elios has simplified the process so the time from resection to injection is approximately two weeks. This makes the vaccine highly feasible and will ultimately be easy for community and academic oncologists to adopt into their practices.

The TLPLDC vaccine is currently being studied as a monotherapy and in combination with standard-of-care checkpoint inhibitor therapies in a Phase IIb clinical trial for the treatment of late-stage melanoma at leading academic cancer centers in the United States.

On February 7, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that additional data will be presented from a cohort of Chinese patients in the Phase III IMbrave150 study that evaluated Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) as a treatment for people with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy (Press release, Hoffmann-La Roche, FEB 7, 2020, View Source [SID1234554001]).

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Data from 194 Chinese patients who took part in the IMbrave150 study were consistent with the global results, that showed a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) compared with standard-of-care sorafenib.

Among Chinese patients, Tecentriq in combination with Avastin reduced the risk of death (OS) by 56% (hazard ratio [HR]=0.44; 95% CI: 0.25–0.76) and reduced the risk of disease worsening or death (PFS) by 40% (HR=0.60; 95% CI: 0.40–0.90), compared with sorafenib. Tecentriq and Avastin were generally well-tolerated with manageable toxicities, and the safety profile was consistent with the known safety profiles of the individual medicines and with the underlying disease.

"Almost half of all cases of hepatocellular carcinoma globally are found in China, so it is extremely encouraging that Chinese patients treated with Tecentriq and Avastin had substantially longer survival outcomes, as compared with the current standard of care in China", said Levi Garraway, M.D., Ph.D, Roche’s Chief Medical Officer and Head of Global Product Development. "We are working closely with the China National Medical Products Administration (NMPA), who recently accepted our supplemental Biologics License Application (sBLA) for the combination, along with global health authorities in the hope of bringing this treatment option to patients as soon as possible."

These data will be presented in the plenary session entitled ‘Round table focus on HCC and transplantation’ at the Liver Cancer Summit 2020, on 8 February at 08:00 am CET.

Every year, more than 750,000 people worldwide are diagnosed with HCC, the most common form of liver cancer – with the majority of cases in Asia and almost half of all cases in China. Elsewhere, incidence of liver cancer is on the rise across Europe and the US, with the number of liver cancer cases in the US more than tripling since 1980.

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies, across several types of lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMbrave150 study
IMbrave150 is a global Phase III, multicentre, open-label study of 501 people with unresectable HCC who have not received prior systemic therapy. People were randomised 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Of 194 Chinese patients (137 from the IMbrave150 global study and 57 from a China extension cohort), 133 were randomised to receive Tecentriq and Avastin and 61 to sorafenib. Tecentriq was administered intravenously (IV), 1200 mg on day 1 of each 21-day cycle, and Avastin was administered IV, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib was administered by mouth, 400 mg twice per day, on days 1–21 of each 21-day cycle. People received the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit, as determined by the investigator. The co-primary endpoints were OS and PFS by independent review facility (IRF) per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Additional study endpoints included overall response rate (ORR), PFS and duration of response (DoR), as measured by RECIST v1.1 (investigator-assessed [INV] and IRF) and HCC mRECIST (IRF), as well as patient-reported outcomes (including time to deterioration of patient-reported quality of life), safety and pharmacokinetics.

Key efficacy endpoint results for OS and PFS (co-primary endpoints) in Chinese patients are shown below:

Tecentriq + Avastin (n=133) Sorafenib
(n=61)
Median OS, months
(95% CI) NE
(13.5–NE) 11.4
(6.7–NE)
OS, HR (95% CI) 0.44
(0.25–0.76)
Median PFS, months
(95% CI) 5.7
(4.2–8.3) 3.2
(2.6–4.8)
PFS, HR (95% CI) 0.60
(0.40–0.90)
NE, not estimable; median follow-up 7.2 months (Tecentriq and Avastin) and 5.6 months (sorafenib); PFS measured as per IRF RECIST v1.1. No formal statistical testing was conducted in the Chinese subpopulation.

Grade 3–4 adverse events (AEs) occurred in 59% of people receiving Tecentriq and Avastin and 47% of people receiving sorafenib. Grade 5 AEs occurred in 2% and 3% of people, respectively.

Key efficacy endpoint results for OS and PFS (co-primary endpoints) for the global population are shown below:

Tecentriq + Avastin (n=336) Sorafenib
(n=165)
Median OS (months)
(95% CI) NE 13.2
(10.4–NE)
OS, HR (95% CI) 0.58 (0.42-0.79)
Log rank p-value 0.0006
Median PFS (months)
(95% CI) 6.8
(5.7–8.3) 4.3
(4.0–5.6)
PFS, HR (95% CI) 0.59 (0.47–0.76)
Log rank p-value <0.0001
NE, not estimable; median follow-up 8.6 months; PFS measured as per IRF RECIST v1.1.
Grade 3–4 adverse events (AEs) occurred in 57% of people receiving Tecentriq and Avastin and 55% of people receiving sorafenib. Grade 5 AEs occurred in 5% and 6% of people, respectively.

About hepatocellular carcinoma
HCC is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.[1] Every year, more than 750,000 people worldwide are diagnosed with HCC,[1],[2] with the majority of cases in Asia and almost half of all cases in China.[2],[3] In the US, the number of liver cancer cases have more than tripled since 1980 and HCC represents the fastest-rising cause of cancer-related death, while in Europe, liver cancer is also on the rise.[4–6] HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage.[1] The prognosis for unresectable HCC remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.[7]

About the Tecentriq and Avastin combination
There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive metastatic triple-negative breast cancer.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasise).

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

On February 7, 2020 eHealth, Inc. (Nasdaq: EHTH), a leading private online health insurance exchange in the United States, reported that the company plans to release fourth quarter and fiscal year 2019 financial results on February 20, 2020 (Press release, eHealthInsurance, FEB 7, 2020, View Source [SID1234554060]).

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Chief Executive Officer Scott Flanders and Chief Financial Officer Derek Yung will host the earnings conference call beginning at 5 p.m. Eastern Time on February 20th to discuss these results.

Individuals interested in listening to the conference call may do so by dialing (877) 930-8066 for domestic callers and (253) 336-8042 for international callers. The participant passcode is 1180328.

A telephone replay will be available two hours following the conclusion of the call for a period of 7 days and can be accessed by dialing (855) 859-2056 for domestic callers and (404) 537-3406 for international callers. The call ID for the replay is 1180328. The live and archived webcast of the call will also be available on the company’s website at www.ehealth.com under the Investor Relations section.

On February 7, 2020 Salarius Pharmaceuticals, Inc. (Nasdaq: SLRX), a clinical-stage oncology company targeting the epigenetic causes of cancer, reported the pricing of an underwritten public offering for gross proceeds of approximately $9.6 million, prior to deducting underwriting discounts and commissions and offering expenses payable by Salarius (Press release, Salarius Pharmaceuticals, FEB 7, 2020, View Source [SID1234554214]).

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The offering is comprised of 7,101,307 Class A Units, priced at a public offering price of $1.15 per unit, with each unit consisting of one share of common stock and a five-year warrant to purchase one share of common stock at an exercise price of $1.15 per share, and 1,246,519 Class B Units, priced at a public offering price of $1.15 per unit, with each unit consisting of one share of Series A convertible preferred stock and a five-year warrant to purchase one share of common stock with an exercise price of $1.15 per share. The convertible preferred stock issued in this transaction includes a beneficial ownership limitation on conversion, but has no dividend rights (except to the extent that dividends are also paid on the common stock), liquidation preference or other preferences over common stock, and has no voting rights. The conversion price of the Series A convertible preferred stock in the offering as well as the exercise price of the warrants are fixed and do not contain any variable pricing features or any price-based anti-dilutive features. The securities comprising the units are immediately separable and will be issued separately.

The closing of the offering is expected to take place on or about February 11, 2020, subject to the satisfaction or waiver of customary closing conditions. In addition, Salarius has granted the underwriter a 45-day option to purchase up to 1,252,173 additional shares of common stock and/or warrants to purchase up to 1,252,173 shares of common stock at the public offering price per share and per warrant, less underwriting discounts and commissions.

Salarius intends to use the net proceeds from this offering for general corporate purposes, including working capital.

Ladenburg Thalmann & Co. Inc., a subsidiary of Ladenburg Thalmann Financial Services Inc. (NYSE American: LTS), is acting as sole book-running manager in connection with the public offering.

The securities were offered pursuant to a registration statement on Form S-1 (File No. 333-235879), which was declared effective by the United States Securities and Exchange Commission ("SEC") on February 6, 2020, and an additional registration statement filed pursuant to Rule 462(b), which became effective on February 7, 2020.

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor will there be any sales of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction. A final prospectus relating to this offering will be filed by Salarius with the SEC. When available, copies of the final prospectus can be obtained at the SEC’s website at www.sec.gov or from Ladenburg Thalmann & Co. Inc., Attn: Prospectus Department, 277 Park Avenue, 26th Floor, New York, New York 10172, by calling (212) 409-2000.