On April 1, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the initial results from a Phase Ib study evaluating the efficacy and safety for the combination of ipatasertib, Tecentriq (atezolizumab) and chemotherapy (paclitaxel or nab-paclitaxel (Abraxane [paclitaxel albumin-bound particles for injectable suspension]) as a first-line treatment option for people with advanced triple-negative breast cancer (TNBC) (Press release, Hoffmann-La Roche, APR 1, 2019, View Source [SID1234534809]). Combination treatment demonstrated a confirmed objective response rate (ORR) of 73% (95% CI 53-88%), irrespective of tumour biomarker status. The median duration of follow-up was 6.1 months (range 3.1–10.6). Grade ≥3 adverse events occurred in 14 people (54%); the most common all-grade adverse events were diarrhea (88%; grade ≥3 19%) and rash (69%; grade ≥3 27%).

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"We are enthusiastic about the potential of this combination in triple-negative breast cancer, an aggressive type of breast cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "These early results support the contribution of ipatasertib to our combination treatment approach in TNBC and reinforce our vision to develop medicines that may benefit patients with this challenging disease."

Preliminary efficacy data for the first 26 patients (18 paclitaxel, 8 nab-paclitaxel) show confirmed responses in 19/26 patients, giving a confirmed ORR of 73%. Responses were seen irrespective of PD-L1 status (9/11 [82%] PD-L1+; 6/8 [75%] PD-L1–; 4/7 [57%] PD-L1 unknown) or PIK3CA/AKT1/PTEN alteration status (5/7 [71%] Dx+, 9/11 [82%] Dx–; 5/8 [63%] Dx unknown).

Activation of the PI3K/AKT pathway has been implicated in resistance to chemotherapies and hormonal therapies in multiple tumour types and loss of PTEN, a negative regulator of AKT, has emerged as a potential mechanism for resistance to checkpoint inhibitor therapy. By inhibiting the PI3K/AKT pathway, ipatasertib may contribute to reversal of T-cell-mediated immunotherapy resistance. These results and the potential benefit that ipatasertib plus the Tecentriq/taxane combination may bring to patients are encouraging and add to the Roche development program in triple-negative breast cancer following the approval of the Tecentriq combination.

Trial enrolment for the Phase 1b study is ongoing. Later this year, Roche will initiate a pivotal multi-center, randomised, double-blind Phase III study investigating the combination of ipatasertib, atezolizumab and paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer.

About the study
The Phase Ib study is an open-label, multicentre study evaluating the safety and efficacy of ipatasertib in combination with atezolizumab and paclitaxel or nab-paclitaxel for patients with locally advanced or metastatic triple-negative breast cancer who have not previously received chemotherapy in the advanced setting. Two triplets: ipatasertib in combination with atezolizumab and paclitaxel (Paclitaxel arm) and ipatasertib in combination with atezolizumab and nab-paclitaxel (nab-Paclitaxel arm) are being evaluated for first-line treatment for advanced TNBC. A second cohort, which is enrolling now, will allow collection of tumour biopsies to assess treatment-related biomarker changes in TNBC patients who have progressed after at least one line of chemotherapy in the advanced setting.

About ipatasertib
Ipatasertib is an oral, highly specific, investigational medicine designed to target and bind to all three isoforms of AKT, which blocks the PI3K/AKT signaling pathway and may prevent cancer cell growth and survival.

Ipatasertib is being studied in tumours that are frequently found to have activation of the PI3K/AKT pathway, including breast and prostate cancers. Pivotal studies are ongoing to evaluate the efficacy and safety of ipatasertib and the opportunity it may provide to address significant unmet needs for patients with these diseases. Ipatasertib has demonstrated clinically meaningful activity in both breast and prostate cancers, with a manageable safety profile.

Ipatasertib was discovered at Genentech in partnership with Array BioPharma Inc.

About Triple-Negative breast cancer
Breast cancer is the most common cancer among women with more than 2 million diagnosed worldwide each year.[1] TNBC represents 15% of all breast cancers and is more common in women under the age of 50, compared with other forms of breast cancer.[2;3;4] It is defined by the lack of expression and/or amplification of the targetable receptors for oestrogen, progesterone and HER2 amplification.[5] Patients with metastatic TNBC generally experience rapid progression and shorter overall survival (OS) compared to other subtypes of breast cancer.[3]

About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough innovations in the HER2 -positive breast cancer. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for all forms of early and advanced breast cancer, including triple-negative and hormone receptor-positive.

Our targeted medicines Herceptin, Perjeta and Kadcyla are continuing to transform the treatment of early and advanced HER2-postive breast cancer and, through our Tecentriq and ipatasertib clinical programmes, we hope to bring new treatment combinations to people with breast cancer, ultimately improving outcomes.

In the United States Tecentriq in combination with nab-paclitaxel is approved for treatment of PD-L1-positive metastatic triple-negative breast cancer. Roche currently has seven phase III studies in TNBC.

On April 1, 2019 TLC (Nasdaq: TLC, TWO: 4152), a clinical-stage specialty pharmaceutical company dedicated to the development and commercialization of novel nanomedicines designed to target areas of unmet medical need in osteoarthritis, pain management, ophthalmology and oncology, reported financial results for the fourth quarter and full year ended December 31, 2018, and provided a business update (Press release, Taiwan Liposome Company, APR 1, 2019, View Source;p=irol-newsArticle&ID=2392882 [SID1234534828]).

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"We had a transformative year in 2018, highlighted by outstanding results from the Phase II clinical trial of our lead program TLC599 for knee osteoarthritis pain, commencement of the first-in-human clinical trial of TLC590 for postsurgical pain management, and completion of a U.S. public offering on Nasdaq," said TLC President George Yeh. "As we move into 2019, we expect to continue to deliver strong progress in our clinical pipeline and company operations by further advancing our lead product candidates closer to pivotal clinical stages while capitalizing on strategic opportunities with our scalable manufacturing capabilities."

Clinical Pipeline Update and Upcoming Milestones

Phase II trial top-line data readout of TLC599 for knee osteoarthritis pain showed significant reductions in pain that sustained through 24 weeks. TLC599 demonstrated statistically significant improvements over placebo, both through 12, 16, 20, and 24 weeks and at every scheduled visit on week 1, 4, 8, 12, 16, 20, and 24. Over half of the patients treated with TLC599 maintained at least a 30% reduction in pain – over twice as many as placebo – throughout the study.

Phase I/II trial top-line data readout of TLC590 for post-surgical pain showed statistically significant and clinically meaningful improvement over the standard of care through 96 hours. In this first-in-human study of TLC590 in patients following inguinal hernia surgery, greater levels of pain reduction were maintained through the entire 168 hours of the study. In the TLC590 group, 58.3% were opioid-free throughout the study. Among those who used opioids, time to first post-surgical use was four times that of the ropivacaine (standard of care) group, and mean total opioid consumption was 54% less.

First patients dosed in Phase II trial of TLC590. The randomized, double-blind, comparator- and placebo-controlled two-part clinical trial will evaluate the safety, pharmacokinetics, and efficacy of TLC590 compared with ropivacaine and placebo in ~200 patients following bunionectomy. Data from Part 1 is expected mid-2019.

TLC178 received clearance from the FDA to initiate Phase I/II clinical trial in pediatric rhabdomyosarcoma. Recruitment of pediatric patients is scheduled to commence once the optimal dose in adults is identified in an analysis scheduled for the second half of 2019.

TLC178 received EMA orphan drug designation for the treatment of soft tissue sarcoma. The designation provides incentives and scientific advice from the EMA during product development phase and 10 years of marketing exclusivity in the EU following product approval. An orphan designation was previously granted by the US FDA, which provides 7 years of marketing exclusivity in the US following product approval.
Corporate Highlights

Completed U.S. IPO. TLC’s American Depositary Shares began trading on The Nasdaq Global Market under the ticker "TLC" on November 21, 2018, becoming the first Taiwan-based biotech company to be listed on Nasdaq. TLC has been listed on the Taipei Exchange since 2012, where it is consistently ranked in the top 5% among all listed companies in corporate governance evaluations.

Appointment of new Chief Medical Officer. Dr. George Spencer-Green, MD, MS, joined TLC in February 2019, bringing experience from serving as VP and clinical head of Pfizer’s biosimilars development program, and as medical director at the likes of Vertex Pharmaceuticals, Abbot Laboratories, and Enbrel, where he led the development of clinical programs, including Humira for rheumatoid arthritis.

Received an upfront payment in March 2019 as part of the commercialization agreement with 3SBio Inc. TLC is eligible for further regulatory and sales milestone payments, as well as a double-digit share of the potential profits from product sales.

Growing global intellectual property protection with 54 granted patents and 68 applications worldwide as of December 31, 2018.
Fourth Quarter and Full Year 2018 Financial Results

Operating revenue for the fourth quarter of fiscal 2018 was NT$17.4 million (US$0.6 million), a 40% increase compared to NT$12.4 million in the fourth quarter of fiscal 2017. Operating expenses for the fourth quarter of fiscal 2018 was NT$326.8 million (US$10.7 million), a 14.2% increase compared to NT$286.1 million in the fourth quarter of fiscal 2017. Net loss for the fourth quarter of fiscal 2018 was NT$306.7 million (US$10.0 million), compared to a loss of NT$262.6 million in the fourth quarter of 2017, or a net loss of NT$5.23 (US$0.17) per share for the fourth quarter of fiscal 2018, compared to a net loss of NT$4.73 per share for the fourth quarter of fiscal 2017.

Operating revenue for the fiscal year 2018 was NT$62.3 million (US$2.0 million), a 25.6% increase compared to NT$49.6 million in the fiscal year 2017. Operating expenses for the fiscal year 2018 was NT$980.3 million (US$32.0 million), a 3.4% increase compared to NT$948.1 million in the fiscal year 2017. Net loss for the fiscal year 2018 was NT$901.6 million (US$29.5 million), compared to a loss of NT$874.0 million in the fiscal year 2017, or a net loss of NT$14.37 (US$0.47) per share for the fiscal year 2018, compared to a net loss of NT$15.75 per share for the fiscal year 2017.

The Company’s cash and cash equivalents and time deposits with maturity over three months (which are classified as "current financial assets at amortized cost" in the Company’s consolidated financial statements) were NT$1,114.6 million (US$36.4 million) as of December 31, 2018, compared to NT$951.7 million at the end of the fourth quarter of fiscal 2017.

On April 1, 2019 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported updated data from the Phase 1/2 KEYNOTE-046 study in metastatic, castration-resistant prostate cancer (mCRPC) (Press release, Advaxis, APR 1, 2019, View Source [SID1234534844]). This trial is being conducted in conjunction with Merck (known as MSD outside the U.S. and Canada) and is evaluating ADXS-PSA, one of Advaxis’ Listeria monocytogenes (Lm)-based immunotherapies, alone and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy.

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Findings will be highlighted in a poster discussion entitled "Effects of ADXS-PSA with or without Pembrolizumab on Survival and Antigen Spreading in Metastatic, Castration-Resistant Prostate Cancer Patients" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting underway in Atlanta. The poster discussion will be held today from 1:00-5:00 p.m. ET and will be led by lead author Mark N. Stein M.D., FACS, Associate Professor of Medical Oncology at Columbia University Medical Center.

KEYNOTE-046 is an open-label, multicenter, dose-determining safety and tolerability Phase 1/2 trial of 50 heavily pretreated patients conducted in two parts (Part A and Part B), with a Phase 2 expansion cohort. The objective of the study is to evaluate ADXS-PSA alone (Part A) and in combination with KEYTRUDA (Part B) for primary endpoints that include safety, tolerability and dosing. Secondary endpoints include anti-tumor activity and progression-free survival, and exploratory endpoints include associations between biomarkers of immunologic response (serum PSA) with clinical outcomes.

"There is a pressing need to improve the care and treatment of patients with metastatic, castration-resistant prostate cancer," said Dr. Stein. "Data from 37 patients in the combination arm of KEYNOTE-046 are promising as a median overall survival of 21.1 months was observed. These results compare favorably to standard-of-care therapy and to study results from similar unselected patient populations with bone-predominant disease, which indicates that this combination warrants further investigation."

Key findings from the combination arm of KEYNOTE-046 include the following:

The majority of treatment-related adverse events consisted of transient and reversible Grade 1-2 chills/rigors, fever, hypotension, nausea and fatigue. The combination of ADXS-PSA and pembrolizumab has been well-tolerated, to date, with no additive toxicity observed.
Median overall survival was 21.1 months at data cutoff (February 1, 2019) (95% CI, range 16.0 months to not-yet-reached) in this dataset of 37 patients.
Correlative immune analyses showed T-cell responses against PSA in 75% of subjects and antigen spreading in 85% of subjects.
Broader immune stimulation, including B-cell activation, was observed in the combination arm (n=37) than in the ADXS-PSA monotherapy arm (n=13).
"We are very excited to report the updated ADXS-PSA data today at the AACR (Free AACR Whitepaper) meeting," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "These data show the clinical potential of ADXS-PSA both alone and in combination with KEYTRUDA. It is meaningful that the combination has been well-tolerated in the study population because dose-related toxicities can present challenges for cancer patients, and an additive therapy with a favorable safety and tolerability profile may offer an attractive option for clinicians if developed further in this indication." He concluded, "Based on the prolonged survival data and strong safety profile to date, we believe that continued clinical development of ADXS-PSA in combination with KEYTRUDA is warranted and represents a potentially significant opportunity for Advaxis."

The full abstract is available at www.advaxis.com and the poster will be available on the Company’s website today at 1:00 p.m. ET.

About KEYNOTE-046

KEYNOTE-046 (NCT02325557) is a Phase 1/2 open-label, multicenter, dose-determination and expansion trial that evaluates the safety, tolerability and preliminary clinical activity of ADXS-PSA as monotherapy (Part A; n=14 [13 treated]), and in combination with KEYTRUDA (Part B; n=37) in heavily pretreated patients with progressive and refractory mCRPC.

About ADXS-PSA

ADXS-PSA, one of Advaxis’ Lm-based immunotherapies, utilizes live, attenuated, bioengineered Lm as a vector to deliver PSA directly to antigen presenting cells. Development is being pursued in a clinical trial collaboration and supply agreement with Merck

On April 1, 2019 Vaccibody AS and Nektar Therapeutics (Nasdaq: NKTR) reported the presentation of new preclinical data for VB10.NEO, a personalized neoantigen cancer vaccine, combined with bempegaldesleukin (NKTR-214 or bempeg), a CD122-preferential IL-2 pathway agonist (Press release, Vaccibody, APR 1, 2019, View Source [SID1234534860]). These data were presented today in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019.

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"We are excited to present these novel preclinical data that show combining bempeg with VB10.NEO synergize to increase both the breadth and the depth of the neoantigen-specific immune response. These unique and non-overlapping mechanisms produced an expansion of the VB10.NEO elicited neoantigen-specific T cells and demonstrated enhanced anti-tumor efficacy in mice. We look forward to evaluating this novel immuno-oncology combination in a clinical study in patients with advanced or metastatic squamous cell carcinoma of head and neck later this year," said Agnete B. Fredriksen, Ph.D., Vaccibody’s President and Chief Scientific Officer.

VB10.NEO is designed to specifically activate a patient’s immune system to tumor-specific antigens, called neoantigens. Bempeg is designed to expand and proliferate tumor antigen-specific T cells in the tumor microenvironment. Addition of bempeg to VB10.NEO is intended to drive maximal expansion of vaccine-induced neoantigen-specific T cells for the treatment of cancer.

"Personalized T cell vaccines could play a critical and central role in cancer immunotherapy," said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar. "These preclinical data highlight the potential of combining a personalized cancer vaccine with a T cell proliferator to induce maximal expansion of vaccine-induced T cell clones and durable responses and specific anti-tumor immunity. We are highly encouraged by these results and look forward to testing this unique approach to personalized cancer treatment in patients with squamous cell carcinoma of the head and neck."

Details of the poster presentation at AACR (Free AACR Whitepaper) are as follows and will be available for download at the time of presentation at View Source and View Source

Abstract #2256
Title: "Combination of neoantigen DNA plasmid vaccine VB10.NEO and NKTR-214, a CD122-biased immunostimulatory cytokine, induces strong neoantigen-specific T cell responses and sustained tumor regression in pre-clinical models"
Session: Clinical Research – Combination Therapies 1
Session Data and Time: Monday, April 1, 2019, 1:00 p.m. – 5:00 p.m. Eastern Time

Combination of VB10.NEO and NKTR-214 synergizes to elicit greater breadth and depth of neoantigen-specific T cell responses than each individual treatment.
The synergistic effect was observed in both CD4 and CD8 T cells, and most pronounced on CD8 T cell responses, further supporting the combination’s potential to induce strong immunogenic CD8+ T cell responses.
VB10.NEO in combination with NKTR-214 and anti-PD-1 induce rapid, complete and durable tumor regression of small tumors and long-lasting stabilization of large tumors supporting the rationale for examining the combination clinically.
In September 2018, Nektar and Vaccibody entered into a clinical collaboration to evaluate bempegaldesleukin in combination with VB10.NEO. A pilot study evaluating the combination in patients with squamous cell carcinoma of the head and neck is planned to begin mid-2019.

About VB10.NEO
VB10.NEO, is a proprietary therapeutic DNA vaccine which uses the patient’s own neoantigens for the personalized treatment of cancer patients. A phase I/IIa neoantigen clinical trial is currently enrolling patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell carcinoma of the head and neck.

About bempegaldesleukin (NKTR-214)
Bempegaldesleukin is an investigational, first-in-class, CD122-preferential IL-2 pathway agonist designed to provide rapid activation and proliferation of cancer-killing immune cells, known as CD8+ effector T cells and natural killer (NK) cells, without over activating the immune system. Bempegaldesleukin stimulates these cancer-killing immune cells in the body by targeting CD122 receptors found on the surface of these immune cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1 In clinical and preclinical studies, treatment with bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3 Bempegaldesleukin has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

On April 1, 2019 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing novel cancer immunotherapies, reported that it has received Advanced Therapy Medicinal Product (ATMP) classification for the Company’s lead investigational product candidate, TAVO (DNA plasmid vector expressing IL-12 gene), as a potential treatment for refractory metastatic melanoma from the European Medicines Agency (EMA) (Press release, OncoSec Medical, APR 1, 2019, View Source [SID1234534811]).

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Only innovative investigational product candidates that are based on gene, tissue or cell therapy are qualified for classification as advanced therapy medicinal products. The classification of TAVO as an ATMP is a significant step toward its potential accelerated approval in Europe. The ATMP classification qualifies TAVO to take advantage of a specific EMA regulatory framework designed to facilitate the accelerated review, approval, and access to innovative products in the European market. Further, OncoSec intends to avail itself of the numerous benefits and incentives for medicinal products undergoing clinical testing and marketing approval processes in Europe. Such incentives include fee reductions and exemptions in pre- and post-marketing authorization phases; administrative, procedural and scientific advice and eligibility for funding.

"The ATMP designation confirms TAVO as an innovative gene therapy potentially offering a groundbreaking new opportunity for the treatment of refractory metastatic melanoma," said Robert Ashworth, PhD, Senior Vice President of Regulatory and Quality at OncoSec.

"Similar to TAVO’s existing FDA Fast Track Designation in the United States, the ATMP designation allows OncoSec to take advantage of a specific European regulatory framework designed to facilitate the accelerated review and approval of TAVO in the European market," said Daniel J. O’Connor, OncoSec’s President and CEO. "Obtaining this important designation delivers on one of OncoSec’s key objectives for 2019."

The Committee for Advanced Therapies (CAT) at the EMA is responsible for classifying and assessing the quality, safety and efficacy of products designated as ATMP. The CAT is a multidisciplinary committee of the best available experts in Europe. The main responsibility of the CAT is to prepare a draft opinion on each ATMP application submitted to the EMA before the Committee for Medicinal Products for Human Use (CHMP) adopts a final opinion on granting a marketing authorization for the product. During drug development, CAT also reviews and certifies the acceptability of quality and non-clinical data.

In February 2017, the U.S. Food and Drug Administration (FDA) designated the investigation of OncoSec’s TAVO in combination with KEYTRUDA (pembrolizumab) to stop or cause the regression of the tumor of patients with Stage III/IV melanoma who are progressing on either KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab) treatment as a Fast Track Development Program. Fast Track designation is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. A drug that receives Fast Track designation is eligible for Accelerated Approval if relevant criteria are met.