On August 28, 2020 Adaptimmune Therapeutics plc ("Adaptimmune")(Nasdaq: ADAP), a leader in cell therapy to treat cancer,reported that data from its Phase 1 trial with SPEAR T-cells targeting AFP at the virtual International Liver Congress (ILC) (Press release, Adaptimmune, AUG 28, 2020, View Source [SID1234564140]). One patient out of four dosed with 5 billion or more cells had a complete response, which was reported previously. The data also demonstrate an acceptable safety profile in patients with hepatocellular carcinoma (HCC).

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"A complete response in a patient with advanced liver cancer, and the anti-tumor activity we have reported in other patients with an acceptable safety profile, to date, further support the continued investigation of ADP-A2AFP," said Elliot Norry, Adaptimmune’s Chief Medical Officer. "We remain encouraged by the potential of this therapy and we are fully committed to developing ADP-A2AFP for people with HCC. We have reported results for four patients at doses of 5 billion cells or more and we are looking forward to sharing more data as we continue to treat patients in the expansion phase of the trial. Further, we continue to review our translational findings and are evaluating ways to improve the therapy, if necessary."

Dr. Bruno Sangro of Clinica Universidad de Navarra presented data from Cohort 3 and the expansion phase of the ADP-A2AFP Phase 1 trial during an oral presentation at ILC. Tim Meyer of University College London presented additional data from Cohorts 1 and 2 during a poster presentation. A video is available on Adaptimmune’s website (View Source) of Elliot Norry, and Mark Dudley, SVP of Early Stage Development, discussing these data. The oral presentation and poster presentation are available online through the congress web site.

Topline data from ILC 1

·One patient had a complete response and also demonstrated a sustained reduction in serum AFP. This patient experienced disease progression, having developed new lesions at Week 32
·Overall, nine patients have been treated as of the data cutoff, of those
-Four patients have been treated with ~5 billion or more transduced cells (three in Cohort 3 and one in the expansion phase): 1 patient with the complete response, 1 with stable disease (SD), and 2 had progressive disease (PD)
-Five patients were previously treated in the first two dose cohorts with doses of 100 million and 1 billion transduced cells, respectively, and all patients had best responses of SD
·ADP-A2AFP SPEAR T-cells were associated with an acceptable safety profile with no evidence of significant T-cell related hepatotoxicity and no protocol-defined dose limiting toxicities
·Evidence of dose-dependent persistence of ADP-A2AFP SPEAR T-cells post-infusion
·Further translational evaluation is ongoing to understand indicators of response

1All data summarized are for patients with HCC with a data cut-off of July 6, 2020. Data from non-HCC patients to be presented at a future congress

Overview of Trial Design

·This is a Phase 1, open-label, dose escalation clinical trial designed to evaluate the safety and anti-tumor activity of ADP-A2AFP in patients with HCC or other AFP-expressing tumors who are not amenable to transplant, resection, or loco-regional therapy, and who failed or were intolerant to or refused standard-of-care treatment
·Dose escalation is complete, and this trial is enrolling in the expansion phase intended to treat up to 25 patients with doses up to 10 billion cells

On August 28, 2020 Merck & Co. reported that Keytruda (pembrolizumab) in combination with Pfizer’s Inlyta (axitinib) has been turned down by NICE as first-line treatment for patients with advanced renal cell carcinoma (RCC) (Press release, Merck & Co, AUG 28, 2020, View Source [SID1234564138]).

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The anti-PD-1 therapy combo was approved in Europe in September 2019 based on findings from the pivotal Phase III KEYNOTE-426 trial, which demonstrated that the drug reduced the risk of death by 47% compared with sunitinib in the indication.

However, NICE says while "short-term clinical trial evidence" shows that the combination is more effective than sunitinib for people with untreated renal cell carcinoma, "it is uncertain if there is a long-term benefit," which means that "cost-effectiveness estimates are uncertain".

Kidney cancer UK has slammed the decision.

"The decision by NICE concerning axitinib and pembrolizumab is extremely disappointing for the kidney cancer community," said the charity’s health professional nurse Susanna Smith.

"This is a combination which showed great results in the clinical trial and has been very well tolerated by people. The combination has been used widely in the US to great success since its approval…so unfortunately this decision will be leave us lagging behind in proving affective, cutting edge treatment options for patients in England and Wales."

"Axitinib and pembrolizumab improves survival significantly and has an important role to play in the treatment of kidney cancer. Rejecting the most active cancer treatments is disappointing for patients," added Professor Thomas Powles, consultant medical oncologist at St Bartholomew’s Hospital, London.

On August 28, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has approved FoundationOneLiquid CDx, Foundation Medicine’s comprehensive pan-tumour liquid biopsy test for patients with solid tumours (Press release, Hoffmann-La Roche, AUG 28, 2020, View Source [SID1234564135]). FoundationOne Liquid CDx is a comprehensive genomic profiling (CGP) test that analyses more than 300 cancer-related genes and multiple genomic signatures to optimise patient care. Cancer is a disease of the genome, driven by genetic mutations within a tumour’s DNA. CGP is used to identify these unique mutations to determine how a tumour behaves and grows, and these insights can help physicians to determine a personalised treatment plan for each individual patient based on the specific mutations identified.

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As well as approving FoundationOne Liquid CDx as a CGP test for patients with any solid tumour, the FDA approved the test for use as a companion diagnostic to identify patients who may benefit from treatment with certain prostate and lung cancer therapies, including Rubraca (rucaparib), a poly (ADP-ribose) polymerase (PARP) inhibitor for treatment in patients with BRCA 1/2-mutant metastatic castration-resistant prostate cancer, and three first-line tyrosine kinase (TKI) inhibitors for the treatment of patients with non-small cell lung cancer. By incorporating multiple genes, including several companion diagnostic biomarkers, the test can help save time versus sequential biomarker testing.

"Many cancer patients are unable to have a tissue biopsy. FoundationOne Liquid CDx may provide a minimally-invasive option for patients who otherwise might not have benefitted from comprehensive genomic profiling," said Levi Garraway, M.D., Ph.D., Roche’s Executive Vice President, Chief Medical Officer, Head of Global Product Development and Co-Founder of Foundation Medicine Inc. "The convenience of testing a blood sample may also enable more rapid treatment decisions, so that patients can feel reassured they are not losing time to fight their disease."

FoundationOne Liquid CDx analyses circulating cell-free DNA from a patient’s blood sample and uses massively parallel sequencing to detect the four main classes of genomic alterations. The test is FDA-approved to report short variants in 311 genes including rearrangements and copy number losses in BRCA1 and BRCA2 genes. The results are delivered in an integrated report that identifies alterations matched to FDA-approved therapies. The report also delivers information about genomic signatures, including microsatellite instability and blood tumour mutational burden, as well as single gene alterations, including all NTRK fusions, to help inform the use of other therapies including immunotherapies, and provides relevant clinical trial information.

"With the acceleration towards precision therapy approaches, it is important that physicians have the highest quality tools that can provide an accurate picture of their patients’ cancers in a timely manner," said Fortunato Ciardiello, M.D., Ph.D, Professor of Medical Oncology, Director of the Division of Medical Oncology at the Università della Campania Luigi Vanvitelli, Italy. "With the approval of FoundationOne Liquid CDx physicians have the choice of two high-quality, FDA-approved comprehensive genomic profiling tests, enabling them to select the most optimal option for their patients."

The FDA approval of FoundationOne Liquid CDx was based on analytical and clinical validation studies including more than 7,500 samples and 30,000 unique variants across more than 30 cancer types. Evaluation of the platform using multiple validation methods across a broad range of tumour types demonstrated high sensitivity and specificity, even at the low allele frequencies often observed in clinical blood samples 1,2.

FoundationOne Liquid CDx is the latest addition to Foundation Medicine’s portfolio of high-quality CGP tests and the second of the company’s CGP tests to receive FDA approval. FoundationOneCDx, Foundation Medicine’s tissue-based genomic test for patients with solid tumours received FDA approval in 2017. Together, these high-quality genomic profiling tests offer physicians important options for detecting specific genomic alterations that help guide efficient, personalised treatment decisions, while reducing the time and sample needed when testing for multiple biomarkers one at a time. FoundationOne Liquid CDx can also provide complementary insights to tissue-based testing regarding tumour heterogeneity (the differences between cancer cells), and clonal evolution (how tumours evolve over time).

About FoundationOneLiquid CDx
FoundationOne Liquid CDx is a qualitative next-generation sequencing based in vitro diagnostic test for prescription use only that uses targeted high throughput hybridisation-based capture technology to analyse 324 genes utilising circulating cell-free DNA (cfDNA) isolated from plasma derived from anti-coagulated peripheral whole blood of advanced cancer patients. The test is FDA-approved to report short variants in 311 genes, including rearrangements and copy number losses in BRCA1 and BRCA2, and is a companion diagnostic to identify patients who may benefit from treatment with specific targeted therapies (listed in Table 1 of the Intended Use) in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Patients who are negative for companion diagnostic mutations should be reflexed to tumour tissue testing and mutation status confirmed using an FDA-approved tumour tissue test, if available. For the complete label, including companion diagnostic indications and complete risk information, please visit www.F1LCDxLabel.com.

On August 28, 2020 Triumvira Immunologics Inc. ("Triumvira"), a privately-held biopharmaceutical company developing a novel platform for engineering T-cells to attack cancers, reported that successfully completed a USD $55 million Series A financing round (Press release, Triumvira Immunologics, AUG 28, 2020, View Source [SID1234564096]). The financing was co-led by Leaps by Bayer, the impact investment unit of Bayer AG, and Northpond Ventures. Additional investors include Oceanpine Capital and Viva Biotech Holdings, and existing investors include Bloom Burton & Co. and the Centre for Commercialization of Cancer Immunotherapy (C3i).

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T-cells are a type of white blood cell that is critical in ridding the body from abnormal and cancerous cells in healthy individuals. In cancer patients, these T-cells frequently fail to either recognize or effectively engage cancer cells. Novel T-cell therapies have the potential to disrupt cancer care and potentially even provide cures. Triumvira is committed to developing novel T-cell therapies that are safer and more efficacious than current cell therapy cancer treatments, including chimeric antigen receptor (CAR) and engineered T-cell receptor (TCR) therapies. This financing will enable Triumvira to advance multiple autologous and allogeneic programs into the clinic for solid tumors and hematologic malignancies.

Curing and preventing cancer is one of the main focus areas of Leaps by Bayer, as this disease still represents one of today’s most pressing health concerns, especially since there are limited curative or preventative therapies available.

"We are very excited about the potential of Triumvira’s platform. It represents a unique opportunity in the development of next-generation cell therapies that promise to address previously incurable cancers," said Juergen Eckhardt, MD, Head of Leaps by Bayer.

"At Northpond we believe that an entirely different construct and mechanism of action is needed for cell therapies to demonstrate activity in difficult-to-treat tumors, particularly solid tumors," said Dr. Michael Rubin, Founder & Chief Executive Officer at Northpond Ventures. "Today’s funding round marks an important milestone in enabling cell therapies to treat a broader array of cancer patients."

"As a co-founder of Triumvira, Bloom Burton is thrilled to see a strong syndicate of investors commit to advancing Triumvira’s novel TAC technology," said Brian Bloom, Chairman & Chief Executive Officer of Bloom Burton & Co. "The execution of Triumvira’s Series A funding further demonstrates Bloom Burton’s unique position to invest in life sciences in Canada and beyond our border."

Triumvira’s foundational technology is the T-cell Antigen Coupler (TAC). TAC is a hybrid molecule comprising multiple protein domains to combine tumor targeting abilities with the T-cell’s own activation machinery, leveraging the potential for the development of superior therapies for a broader range of patients with solid or liquid malignancies. Triumvira’s preclinical data with autologous and allogeneic programs demonstrate unique biological differences between TAC-engineered T-cells and second-generation CAR-T cells, with TAC-T cells showing absence of tonic signaling, strong tumor penetration, and long-term persistence. These functional properties help TAC T-cells produce strong anti-tumor activity and no evidence of toxicity, particularly in models of solid tumors.

"With so many engineered T-cell therapy companies developing new T-cell technologies, it is all about differentiation," said Dr. Paul Lammers, President and CEO of Triumvira. "We are excited to have a strong group of investors join our Series A syndicate, who believe in the promise of our proprietary TAC technology, which incorporates an innovative, well-differentiated, and patented design. As we develop our technology that has the potential to be used in treating both hematological and solid tumors, we hope to show that differentiation in clinical trials soon and provide a significant benefit to cancer patients."

Dr. Juergen Eckhardt and Dr. Jak Knowles will represent Leaps by Bayer by actively participating on Triumvira’s board of directors together with Dr. Shaan Gandhi, Principal at Northpond Ventures. Additionally, Scott Smith, current President at BioAtla and former President and Chief Operating Officer at Celgene, has been named Chairman of the Board. Brian Bloom, Dr. Paul Lammers, Dr. John Holyoake, and independent Director Cynthia Collins, President & CEO at Editas Medicine, will remain on the Triumvira board.

Wedbush PacGrow acted as the exclusive placement agent for the Series A financing. Shanghai Elite Choices LLC served as an advisor to Triumvira.

On August 27, 2020 Sysmex Inostics, Inc., a global leader and pioneer in blood-based circulating tumor DNA (ctDNA) analysis for oncology, reported the publication of a clinical study evaluating RAS mutation status in circulating tumor DNA (ctDNA) of colorectal cancer (CRC) patients undergoing anti-EGFR antibody therapy (cetuximab or panitumumab) rechallenge using the OncoBEAM RAS CRC test in two different multicenter Japanese retrospective trials, JACCRO CC-08 and JACCRO CC-09 (Press release, Sysmex Inostics, AUG 27, 2020, View Source [SID1234568255]).

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OncoBEAM RAS CRC is a test that uses BEAMing technology, an enhanced digital PCR method optimized for high sensitivity blood-based mutation detection for metastatic colorectal cancer (mCRC) patients. In this study, investigators utilized the highly sensitive nature of OncoBEAM testing to explore the clinical value of monitoring changes in plasma RAS mutations in CRC patients during treatment with anti-EGFR antibody therapy.

Colorectal cancer continues to be one of the leading causes of cancer-related deaths globally. Treatment of mCRC patients with anti-EGFR monoclonal antibodies have demonstrated significant improvements in the survival of patients with wild-type RAS tumors. mCRC patients being considered for anti-EGFR therapy rechallenge could greatly benefit the overall patient survival by undergoing initial plasma testing to establish RAS mutation status at baseline, as well as performing subsequent tests to monitor RAS mutation dynamics during treatment. By receiving regular blood draws throughout the anti-EGFR rechallenge treatment, patients would benefit from periodic OncoBEAM RAS testing, which would in turn deliver valuable insights for clinicians in assessing therapy response.

The study published in JCO Precision Oncology by Sunakawa et al., demonstrated that RAS mutations were found in 38% of CRC patients after receiving the first course of anti-EGFR mAb therapy, but prior to rechallenge treatment. The disease control rate (DCR) was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation detected by OncoBEAM at baseline. The data also showed that patients with RAS mutations detected just before anti- EGFR mAb rechallenge had no survival benefit from rechallenge treatment. Moreover, post-progression survival time after rechallenge was worse in patients with RAS mutations than in patients without mutations at disease progression. The emergence of RAS mutations during rechallenge treatment at disease progression is therefore useful for predicting outcomes of anti- EGFR mAb therapy rechallenge.

"We found that the OncoBEAM RAS CRC assay was not only effective in monitoring the resistance to anti-EGFR therapy, but was also important in helping us determine the efficacy of the rechallenge treatment and therefore predict patients who would have favorable outcomes. Overall, our novel findings support the value of using the ultrasensitive OncoBEAM RAS liquid biopsy test in the clinical management of CRC patients receiving anti-EGFR mAb as rechallenge treatment. " stated Dr. Yu Sunakawa, MD, PhD, Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan.

Besides results of this publication, a new prospective observational trial "REMARRY (UMIN000036424)" has been initiated with over 100 patients recruited as of June 2020. This clinical trial, supported by SCRUM-Japan MONSTAR-SCREEN, will expand the evaluation of patient-specific dynamics in ctDNA RAS mutational status as a predictor of anti-EGFR mAb rechallenge efficacy. Overall, the aggregate results from these trials should strongly support the clinical utility of performing longitudinal plasma OncoBEAM RAS testing in monitoring tumor response during anti-EGFR antibody therapy.

The publication, titled "RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment with Anti-EGFR Antibodies in Patients with Metastatic Colorectal Cancer," was published in JCO Precision Oncology, July 28, 2020, by Yu Sunakawa et al.: View Source

The poster, titled "REMARRY and PURSUIT trials: Liquid biopsy-guided rechallenge of anti-EGFR monoclonal antibody for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer" was presented at ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer 2020 by Hiromi Nakajima et al.: View Source