Sysmex Inostics presents data at ASCO showing HPV-SEQ, a new CLIA-validated SafeSEQ NGS HPV16/18 liquid biopsy assay, is highly effective for measuring HPV DNA in the plasma of patients with oropharyngeal squamous cell carcinoma (OPSCC) enrolled in the OPTIMA 2 treatment de-escalation trial

On June 2, 2021 Sysmex Inostics, Inc., a global leader in the liquid biopsy revolution for oncology, reported that it is presenting the poster entitled, "Ultra-sensitive detection and quantification of human papillomavirus (HPV) DNA in the plasma of patients with oropharyngeal squamous cell carcinoma (OPSCC) enrolled in the OPTIMA 2 treatment de-escalation trial" at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, June 4-8, 2021 (Press release, Sysmex Inostics, JUN 2, 2021, View Source;301303731.html [SID1234583425]). The featured data show that SafeSEQ cfHPV-DNA Test (HPV-SEQ) exhibits robust quantitative detection of cell-free HPV DNA (cfHPV-DNA) across a broad dynamic range, enabling high-resolution monitoring for patients with HPV+ OPSCC, a type of head and neck cancer. The ASCO (Free ASCO Whitepaper) presentation coincides with the launch of HPV-SEQ as the newest CLIA validated assay in the Sysmex Inostics portfolio of ultra-sensitive SafeSEQ NGS panels.

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HPV 16 and HPV 18 are the two most common high-risk HPV strains, and persistent infections can lead to HPV-related cancers, including cervical, anal, and head and neck cancers. HPV driven tumors are increasing in prevalence, especially in patients presenting with head and neck cancer.1 cfHPV-DNA can be measured in patients’ plasma as a non-invasive surrogate of tumor burden and can facilitate precise tracking of disease response throughout treatment.

Sysmex Inostics has introduced HPV-SEQ, an ultra-sensitive blood-based liquid biopsy solution for identifying and accurately quantifying circulating HPV 16 and HPV 18 DNA in patients with HPV-related cancers.

As patients with HPV-driven tumors often have a good prognosis, clinical investigators have recently explored new strategies for treatment de-escalation to avoid unnecessary side-effects caused by overtreatment. Important clinical data for HPV-SEQ was generated during the recent OPTIMA 2 phase II trial (NCT03107182) investigating induction chemoimmunotherapy followed by risk/response stratified de-escalated locoregional therapy for patients with HPV+ OPSCC. During the trial, HPV-SEQ was employed to evaluate levels of cfHPV-DNA alongside patients’ radiographic response to therapy in order to assess the future utility in guiding treatment de-escalation strategies. HPV-SEQ showed robust quantitative detection of HPV 16/18 across a broad dynamic range over five orders of magnitude with low quantitative variability. Importantly, a high correlation was observed between dynamic changes in patients’ cfHPV DNA levels and radiographic responses following induction therapy.

"HPV-SEQ exhibits robust quantitative detection of HPV, even when only a few copies are present, thus potentially enabling precise molecular monitoring of patients’ therapy response," said Dr. Nishant Agrawal, Professor of Surgery at the University of Chicago. Dr. Agrawal added, "We see the HPV-SEQ test becoming an important tool for refining patient treatment strategies and accelerating the development of novel de-escalation approaches for the treatment of HPV-associated OPSCC."

Poster number 6048, "Ultra-sensitive detection and quantification of HPV DNA in the plasma of patients with oropharyngeal squamous cell carcinoma (OPSCC) enrolled in the OPTIMA 2 treatment de-escalation trial," presented by Hillary Sloane, PhD, Associate Director of Medical & Scientific Affairs at Sysmex Inostics, will be available June 4 through June 8, 2021 during the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

Currently, HPV-SEQ is being used in prospective studies to further evaluate the kinetics of cfHPV-DNA as a predictor of response to therapy in patients with HPV+ OPSCC and other HPV-related cancers. HPV-SEQ is CLIA-validated and available to support clinical trials through the Sysmex Inostics turnkey testing service in their CLIA lab located in Baltimore, Maryland.

1. Van Dyne EA, Henley SJ, Saraiya M, Thomas CC, Markowitz LE, Benard VB. Trends in Human Papillomavirus–Associated Cancers — United States, 1999–2015. MMWR Morb Mortal Wkly Rep 2018;67:918–924.

Mirati Therapeutics to Take Part in the 42nd Annual Goldman Sachs Global Healthcare Conference

On June 2, 2021 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported that it will take part in a fireside chat at the 42nd Annual Goldman Sachs Global Healthcare Conference, which will be webcast on June 9 (Press release, Mirati, JUN 2, 2021, View Source [SID1234583424]). Charles M. Baum, M.D., Ph.D., president and chief executive officer, will answer questions about the company at 3:50 p.m. E.T./12:50 p.m. P.T.

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The webcast will be available through the "Investors" section of the Mirati website, Mirati Investor Events and Presentations, and a replay of the webcast will be made available for 90 days following the event.

First Patient Dosed in QBiotics & MSD Clinical Trial Collaboration for Unresectable Melanoma

On June 2, 2021 QBiotics Group Limited (QBiotics), a life sciences company developing novel small molecule anticancer and wound healing pharmaceuticals, reported that it has dosed the first patient in the Phase Ib/IIa clinical trial of the company’s lead oncology molecule, tigilanol tiglate in combination with MSD’s immune checkpoint inhibitor KEYTRUDA (pembrolizumab) for patients with unresectable melanoma, the deadliest form of skin cancer (Press release, QBiotics, JUN 2, 2021, View Source;msd-clinical-trial-collaboration-for-unresectable-melanoma-301304596.html [SID1234583423]).

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The QB46C-H06 multi-centre, open label study will enrol approximately 22 patients with Stage IIIB to IV M1c-melanoma across a number of Australian sites over 24 months. The study will test up to three intratumoural doses of tigilanol tiglate at three escalating dose levels, administered 3 weeks apart in combination with intravenous pembrolizumab administered every 3 weeks for up to 24 months. The study will evaluate the safety, optimal dose and tumour response of the tigilanol tiglate and pembrolizumab combination in patients with late-stage unresectable melanoma, who have been previously exposed to immune checkpoint inhibitors.

Dr Victoria Gordon, Managing Director and CEO of QBiotics, said "We are very pleased to be collaborating with MSD in the fight against melanoma, a deadly form of skin cancer prevalent worldwide, but especially so here in Australia.

Dr Gordon continued "Patients with unresectable melanoma who have received prior checkpoint inhibitors currently have limited effective treatment options. We hope to see that when combined, tigilanol tiglate and KEYTRUDA may produce additive anti-tumour immune responses, improving outcomes for patients."

Over the last decade, the global cases of melanoma have increased by nearly 50 percent, with more than 320,000 people diagnosed annually. This translates to approximately 60,000 melanoma-related deaths per year[1]. Australia has the highest melanoma rates in the world, with one person diagnosed every 30 minutes, and an estimated 1,300 deaths each year.[2]

Tigilanol tiglate is a plant-derived small molecule, administered by injection directly into a solid tumour. Injected tumours are rapidly destroyed by tumour cell necrosis, vascular disruption, and immune-mediated mechanisms.[3] Pembrolizumab is a systemic immune checkpoint inhibitor, which reactivates the immune system by blocking the activity of PD-1, an immune checkpoint protein that prevents T cells from recognising and killing cancer cells.[4]

"The commencement of this trial with our first patient dosed is a significant milestone for QBiotics and is underpinned by positive outcomes from our Phase I QBC46-H01 Phase I study using tigilanol tiglate as a monotherapy in 22 patients with a broad range of refractory solid tumours. In this Phase I study a single injection of tigilanol tiglate showed an injected tumour response rate of 60% (CR of 20%, PR of 28%, SD of 12%).[5] Non-injected (abscopal) responses in distal tumours were observed in two patients with melanoma[6]," said Dr Gordon.

ABOUT TRIAL NCT04834973

A Phase Ib/IIa, multicentre, open label, dose-escalation study to evaluate the safety, tolerability, and preliminary effectiveness of intratumoural tigilanol tiglate in combination with intravenous pembrolizumab in adult patients with unresectable, Stage IIIB to IV M1c melanoma.

The primary objectives are 1. To determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) level of a single intratumoural injection of tigilanol tiglate administered in combination with intravenous pembrolizumab (200 mg), and 2. To assess the safety and tolerability of i) A single injection of tigilanol tiglate at escalating dose levels (dose-escalation) administered in combination with pembrolizumab; and ii) Repeat injections of tigilanol tiglate (maximum of 3) administered in combination with pembrolizumab. Secondary objectives include tumour responses according to RECIST 1.1 criteria, including loco-regional control of injected tumour(s) and non-injected tumour(s), and survival in patients. For more information, visit View Source

Clinical Trial Results of the BCMA CAR-T Co-developed by Innovent and IASO Biotherapeutics Commented in American Society of Hematology’s Medical Journal "Blood"

On June 2, 2021 Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, together with IASO Biotherapeutics (IASO Bio), reported that the results of initial clinical studies on treatment of relapsed or refractory multiple myeloma (R/R MM)in subjects using fully human BCMA-targeting CAR, an investigational chimeric antigen receptor (CAR) T-cell therapy co-developed by IASO Bio and Innovent (Innovent: IBI326, IASO Bio: CT103A) was published in "Blood", a peer-reviewed medical journal specializing in hematology (Press release, Innovent Biologics, JUN 2, 2021, https://www.prnewswire.com/news-releases/clinical-trial-results-of-the-bcma-car-t-co-developed-by-innovent-and-iaso-biotherapeutics-commented-in-american-society-of-hematologys-medical-journal-blood-301304643.html [SID1234583422]). The name of the article is "A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma." The editors of "Blood" were so impressed by the unique persistence of IBI326 and the authors’ exposition on the re-treatment prospects of the disease during the studies that they invited experts from University College London Cancer Institute to write a review entitled "BCMA CARs in multiple myeloma: room for more" (DOI 10.1182/blood.2021010833).

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Background and results of IBI326 clinical studies:

Despite recent advances in multiple myeloma (MM) treatment strategies, particularly the emergence and clinical application of immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies that have improved the survival of MM, it remains an incurable plasma cell cancer, and relapse is almost inevitable in all patients. Results from previously published clinical trials showed that; 33% to 88% of patients with relapsed/ refractory MM (R/R MM) had objective antimyeloma responses after treatment with anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells 1-7. However, it remains a great challenge to achieve durable responses, and relapse or disease progression is observed in 28% to 88% of patients at a median follow-up time of 2 to 15 months 1-7.

The clinical study published in "Blood" was conducted in Department of Hematology, Tongji Medical College of HUST in China (ChiCTR1800018137). The results showed IBI326 has favorable safety profile with mild and controllable cytokine release syndrome (CRS). IBI326 shows excellent expansion and longer persistence during transfusion. In addition, subjects relapsed from a prior murine BCMA CAR-T treatment were also benefited from IBI326.

Efficacy:

IBI326 is highly active and induces quick and durable responses in subjects with R/R MM.
The ORR was 100% for all patients (18 of 18), with enhanced responses over time, and 72% (13 of 18) of the patients achieved complete response (CR) or stringent complete response (sCR). All patients evaluated for minimal residual disease (MRD, 17 of 17) in the bone marrow were MRD-negative at 10-4 nucleated cells by flow cytometry within 1 month; 9 of them were tested by next generation sequencing, and 4 patients achieved the best responses of MRD negativity by the level of 10-6 nucleated cells over time. The PFS and OS rate at 1 year were 58.3% and 75%, respectively. 1 year PFS rate was 79.1% for subjects without extramedullary myeloma (EMM). The patient with longest follow-up maintains sCR for over 2 years.
This study enrolled 4 patients who had previously been treated with a murine BCMA CAR for the 4 murine BCMA CAR-exposed patients. 3 achieved sCR, and 1 achieved a very good partial response (VGPR).
Safety: No Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in any of the dose groups. CRS was observed from 94% of the subjects, and there was a comparatively high rate of severe CRS (28% grade 3; 13% would have had grade 3 if the highest dose had been excluded). In dose expansion study, investigator recommended 1X106/kg CAR+ T cells as recommended Phase II dose.

CAR T-cell expansion: According to ddPCR-based CAR transgene quantification, the median time to reach peak concentration after infusion was 12 days (range, 7-26 days), a strong indication of rapid CAR expansion. No significant difference was observed among 3 dosing groups. For the 4 patients who had participated in prior murine BCMA CAR T-cell trials, low levels of expansions of previously infused murine CAR T cells were observed with short durations compared with IBI326, indicating that the therapeutic response should mainly be attributed to IBI326 expansion.

Immunogenicity: ADA was tested in all 18 subjects and two samples of one subject were validated as positive for ADA.

Comments on the "Blood" article :

In the article, 3 experts from University College London (UCL) Cancer Institute, Lydia Sarah, Hui Lee and Kwee L. Yong commented on the IBI326 studies (as "CT103" in the article). "Wang et al describe clinical outcomes that we have come to expect in the field today and include sufficient details on their trial protocol and subject cohort to allow considered comparison with other trials globally. The authors are candid in their assessment of the trial, and they discuss the possible impact of their comparatively treatment-naive cohort and their lymphodepletion regimen (combining fludarabine with high-dose cyclophosphamide) on response, toxicity, and CAR persistence. Even so, the study is noteworthy for the duration of CAR persistence and its inclusion of subjects previously treated with a murine BCMA CAR."

They also mentioned that both points are significant because it is well known that CARs targeting CD19 in acute lymphocytic leukemia (ALL) can maintain durable responses in 40% of subjects despite therapy being given for refractory disease and multiple relapses8. However, even with initial disease regression, durable responses with CAR T cells have not been achieved in MM 9-11. In the first 2 BCMA CAR trials reported, subjects had a median PFS of 1 year. Although the outcomes reported in the CARTITUDE-1 trial were better, it is still not clear whether prolonged remissions can be obtained with existing CAR T-cell products in MM.

The experts subsequently noted and affirmed the in vivo persistence of IBI326. They compared the clinical trial data for CT103 and 2 other CAR-T drugs launched in the market. "In trials assessing the earliest BCMA CARs, bb2121 and LCAR-B38M/JNJ-4528, persistence was typically 6 months. Given this landscape, the reported persistence of CT103 is notable. The maximum concentration of circulating CT103 is lower than other CARs, but it has a median persistence of 308 days, which will likely increase with follow-up. Robust expansion was seen in all subjects, and at last follow-up (median, 13 months), CAR T cells had fallen below 1 X 102 copies per mg of DNA in only 5 subjects."

In addition to relatively high persistence, the experts also noted relative low binding affinity (10 nM) of CT103. "Another unusual feature of CT103 is its relatively low binding affinity (10 nM), which the authors have usefully compared with that of bb2121. CT103 has a slower on-rate, and both binders have similarly fast off-rates compared with the CD19 binder in tisagenlecleucel and axicabtagene ciloleucel (ie, FMC63). The association between binding affinity and clinical outcomes is still uncertain and is likely to be target and context dependent. In CD19, a lower-affinity CAR has been associated with improved persistence in pediatric ALL in which the authors postulated that a faster off-rate may facilitate serial triggering. More work is needed to define the binding kinetics that may influence the efficacy of BCMA CARs."

They also made special mention of the unusual practice of enrolling 4 subjects who had previously been treated with a murine BCMA CAR for CT103 clinical trials. "Unusually, this study enrolled 4 subjects who had previously been treated with a murine BCMA CAR. CT103 expanded in all 4 subjects, and in 3 of them, there was transient and low-level expansion of the murine BCMA CAR construct after lymphodepletion. This indicates that undetectable levels of CAR T cells can remain at disease relapse with antigen-positive disease, but they are likely to be exhausted or terminally differentiated. This further underlines the importance of defining the drivers of disease control in terms of CAR manufacture or in the tumor niche."

The experts from UCL Cancer Institute ended with positive remarks and optimism on the persistence of CT103 and its treatment of MM, "More widely, we are witnessing rapid developments in MM CAR T-cell therapy. We await maturity of promising but early data from an increasing number of MM CARs jostling for a spot on the global landscape, some of which may achieve persistence to rival CT10313. CT103 thus enters a rather crowded field but is a welcome addition for its report of increased persistence and contribution to the discussion surrounding the prospect of retreatment."

About IBI326 (BCMA CAR-T)

IBI326 is an innovative therapy co-developed by Innovent and IASO Bio. Previous studies indicate subjects with relapsed/refractory multiple myeloma (R/R MM) who received high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells will not be effective. To solve this dilemma, IBI326 has been developed, a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3ζ activation domains. Based on strict selection and screening, utilizing a proprietary in-house optimization platform, the construct of the BCMA CAR-T is potent and persistent. In February 2021, IBI326 was granted breakthrough therapy designation by the NMPA for the treatment of relapsed/refractory multiple myeloma.

Labcorp to Introduce Combined Oncology Offering at 2021 ASCO® Annual Meeting

On June 2, 2021 Labcorp (NYSE: LH), a leading global life sciences company, reported the introduction of its combined Labcorp oncology platform at the virtual 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 4-8 (Press release, LabCorp, JUN 2, 2021, View Source [SID1234583420]).

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Labcorp’s oncology platform brings together the company’s leadership in diagnostic testing with its comprehensive drug development services, delivering targeted solutions for oncology by leveraging breakthrough science and insights from clinical and patient data to power better decisions and improved patient outcomes. Labcorp’s highly trained and specialized oncology team is led by Prasanth Reddy, M.D., MPH, a triple-board certified oncologist, and includes Robert Phillips, Ph.D., vice president and head of enterprise oncology.

"Advances in science have led to promising cancer-related discoveries, yet there is much more to do to in the field of oncology to find better treatments and improve lives," said Phillips. "Labcorp has a history of developing best-in-class diagnostics and drug development solutions that can help accelerate new therapy options for cancer patients. We are able to empower better decisions and make precision medicine available to more cancer patients by expanding access to diagnostic testing and clinical trial opportunities across communities."

Phillips will speak as part of the Industry Expert Theater1 on Monday, June 7, from 10-10:40 a.m. EDT. His presentation, Reimagining Precision Medicine Throughout a Patient’s Journey, will introduce the Labcorp oncology platform and highlight new, expanded testing and trial options. Immediately following the presentation, Phillips will be conducting a live audience Q&A session. Attendees will also have on-demand access to the presentation for the duration of the conference. Labcorp’s online exhibit for the ASCO (Free ASCO Whitepaper) Annual Meeting is available 24/7 between Friday, May 14, and Tuesday, July 6. The exhibit aims to educate attendees on testing options offered by Labcorp, as well as the wide-ranging support the company provides for oncology clinical trials. Attendees will be able to leave a virtual business card at the exhibit page to connect with Labcorp. To access the online exhibit and Dr. Phillips’ presentation, and to learn more about the conference, please visit View Source

Labcorp’s comprehensive oncology test menu to be discussed at the ASCO (Free ASCO Whitepaper) Annual Meeting includes the commercial introduction of OmniSeq INSIGHT—a pan-cancer, tissue-based sequencing test for patients with late-stage solid tumor cancers. The test helps physicians make decisions about therapeutic treatments and identify patients who may be eligible for any of several thousand ongoing clinical trials.

Labcorp also intends to highlight IntelliGEN Myeloid and liquid biopsy testing for lung cancer. IntelliGEN Myeloid is a next-generation sequencing (NGS) assay that evaluates 50 genes known to be useful in providing diagnostic, prognostic and predictive information for patients with myeloid malignancies. Liquid biopsy testing examines a blood sample for cancer cells, or pieces of DNA from a tumor circulating in the blood, in order to identify mutations and help select the most effective, targeted treatments. It is an increasingly viable, non-invasive testing option in cases where obtaining a tissue sample may be difficult or risky.

Labcorp Drug Development will contribute two online abstracts to the scientific program—e18608: "Mortality in adult patients with solid or hematological cancers and SARS-CoV-2 infection with a specific focus on lung and breast malignancies: A systematic review and meta-analysis," and e13584: "The role of digital clinical measures in improving cancer care and research."

Labcorp has also made a donation to Conquer Cancer, the ASCO (Free ASCO Whitepaper) foundation dedicated to conquering cancer throughout the world by funding breakthrough research and sharing cutting-edge knowledge.