On May 29, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that new and updated analyses on the ongoing studies of savolitinib and surufatinib at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program, May 29-31, 2020 (Press release, Hutchison China MediTech, MAY 29, 2020, https://www.chi-med.com/chi-med-to-discuss-select-global-clinical-trial-data-presented-at-asco20/ [SID1234558740]). Chi-Med will hold a conference call and audio webcast on Monday, June 1, 2020, at 1 p.m. GMT / 8 a.m. EDT / 8 p.m. HKT to review select clinical data and discuss development plan next steps.

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A live audio webcast of the call will be broadcast via Chi-Med’s website at www.chi-med.com/event. Investors may participate in the call using one of the following dial-in numbers: 1‑866‑213‑0992 (U.S. toll-free) / 0800‑032‑2849 (U.K. toll-free) / +852-2112-1888 (Hong Kong). Additional dial-in numbers are also available at Chi-Med’s website. Please use participant access code "6929001#."

Savolitinib, a potent, highly selective oral inhibitor of mesenchymal epithelial transition receptor ("MET")

In clinical studies to date, involving over 1,000 patients, savolitinib has shown promising clinical efficacy in patients with MET gene alterations in multiple tumor types with an acceptable safety profile.

Presentation Title: Phase II study of savolitinib in patients with pulmonary sarcomatoid carcinoma ("PSC") and other types of non-small cell lung cancer ("NSCLC") harboring MET exon 14 skipping
Authors: S Lu, J Fang, X Li, L Cao, J Zhou, Q Guo, Z Liang, Y Cheng, L Jiang, N Yang, Z Han, J Shi, Y Chen, H Xu, H Zhang, D Zhang, J Li, L Wang, Y Ren, W Su
Abstract Link: 9519
This is an ongoing China Phase II study of savolitinib monotherapy in NSCLC patients with MET exon 14 skipping mutations who have failed prior systemic therapy or are unable to receive chemotherapy (clinicaltrials.gov number NCT02897479), in which savolitinib demonstrated promising anti-tumor activity and acceptable tolerability. Approximately 35% of patients in the study have an aggressive subtype of NSCLC, PSC).[i] Treatment naïve patients accounted for approximately 40% of the treated patients while the remainder received prior treatments.

As of March 31, 2020, confirmed responses were seen in 49.2% of efficacy evaluable patients and disease control were seen in 93.4% of efficacy evaluable patients.

Data were not mature for Duration of Response ("DoR"), Progression Free Survival ("PFS") and Overall Survival ("OS"). Median DoR was 9.6 months (95% confidence interval ["CI"] 5.5–not reached ["NR"]) with maturity of 40%. Median PFS was 6.9 months (95% CI 4.2–19.3) with maturity of 50%. Median OS was 14.0 months (95% CI: 9.7–NR) with maturity of 46%. Efficacy observations were consistent across subgroups in this analysis.

Clinical data indicate an acceptable safety profile of savolitinib in patients with locally advanced or metastatic NSCLC who had MET exon 14 skipping mutations, with a low rate of adverse event ("AE") related discontinuations of 14.3%.

On May 29, 2020, a new drug application ("NDA") for savolitinib in this setting was accepted for review by the China National Medical Products Administration.

Presentation Title: SAVOIR: A phase III study of savolitinib versus sunitinib in patients with MET-driven papillary renal cell carcinoma ("PRCC")
Authors: TK Choueiri, DYC Heng, JL Lee, M Cancel, RB Verheijen, A Mellemgaard, L Ottesen, MM Frigault, A L’Hernault, Z Szijgyarto, S Signoretti, L Albiges
Abstract Link: 5002
In this global study of savolitinib monotherapy compared with sunitinib in patients with MET-driven, locally advanced or metastatic PRCC, savolitinib demonstrated encouraging efficacy and an improved safety profile versus sunitinib (NCT03091192). This Phase III study was stopped in late 2018 due to confounding results from a separate, external, retrospective observational study. 60 randomized patients (33 savolitinib, 27 sunitinib) were followed through August 19, 2019. Although patient numbers and follow-up were limited, savolitinib demonstrated encouraging efficacy versus sunitinib, with fewer grade ≥3 AEs and fewer dose modifications. Based on these data, AstraZeneca and Chi-Med are actively evaluating the opportunity to restart clinical work in PRCC for monotherapy savolitinib.

Savolitinib patients had not reached median OS at data cut-off, compared to 13.2 months for sunitinib patients (hazard ratio ["HR"] 0.51; 95% CI: 0.21–1.17; p=0.110). Median PFS was 7.0 months for savolitinib patients, compared to 5.6 for sunitinib patients (HR 0.71; 95% CI 0.37–1.36; p=0.313).

Responses were observed in 27% and 7% of savolitinib and sunitinib patients, respectively. This difference did not reach statistical significance due to the small sample size. None of the 9 responders on savolitinib treatment experienced disease progression as of data cut-off, compared to 1 of 2 responders on sunitinib treatment. Sunitinib response rate was in range with previous studies.[ii],[iii]

Grade ≥3 AEs were reported in 42% of savolitinib patients versus 81% of sunitinib patients, with AEs leading to dose modification in 30% and 74% of savolitinib and sunitinib patients, respectively.

Surufatinib, an oral selective inhibitor of vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), and colony stimulating factor-1 receptor (CSF-1R)

In clinical studies to date, involving over 900 patients, surufatinib has demonstrated robust efficacy and safety profile, including in two randomized, double-blind, placebo controlled, multi-center Phase III studies in pancreatic neuroendocrine tumor ("pNET") and non-pancreatic (extra-pancreatic) neuroendocrine tumor patients ("epNET"). In the U.S. surufatinib was granted Fast Track Designations for development in pNET and epNET, and Orphan Drug Designation for pancreatic NET. In China a New Drug Application ("NDA") is under review and a second is in preparation.

Presentation Title: Efficacy and safety of surufatinib in U.S. patients with neuroendocrine tumors ("NET")
Authors: A Dasari, D Li, MW Sung, C Tucci, JS Kauh, MK Kania, AS Paulson
Abstract Link: 4610
Preliminary data from the two NET cohorts in the ongoing US Phase Ib trial for surufatinib demonstrated promising efficacy irrespective of prior lines of therapy, with a manageable safety profile comparable with the larger pool of surufatinib safety data (NCT02549937).

As of April 21, 2020, 16 patients with pNET were treated for a median of 7.1 months (range 2.0-17.5) and 16 patients with epNET were treated for a median of 4.9 months (range of 1.0-10.2). All 32 patients have pretreated progressive NETs (median prior lines of treatment: 3; range 1-8).

Confirmed response was observed in 18.8% of pNET patients; all remaining patients have stable disease (including 1 unconfirmed response), for disease control rate ("DCR") of 100%. In the epNET cohort all patients had stable disease (including 1 unconfirmed response).

On May 29, 2020 Marker Therapeutics, Inc. (Nasdaq:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported updated clinical results from an ongoing investigator-sponsored Phase 1 trial led by the Baylor College of Medicine, evaluating the Company’s MultiTAA-specific T cell therapy in patients with advanced or metastatic pancreatic adenocarcinoma (Press release, TapImmune, MAY 29, 2020, View Source [SID1234558739]). Data from a cohort of patients receiving MultiTAA-specific T cell therapy in combination with standard-of-care chemotherapy in the first-line setting (Arm A), were reviewed today by lead investigator, Brandon G. Smaglo, M.D., FACP, as part of a poster session during the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting. ASCO (Free ASCO Whitepaper) is being held from Friday, May 29 through Sunday, May 31, 2020.

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"Pancreatic cancer is one of the most deadly forms of cancer today, with the mortality rate remaining relatively unchanged over the past several decades despite ongoing research and treatment advances," said Dr. Brandon G. Smaglo. "With a growing body of data, we continue to be encouraged by the potential of MultiTAA-specific T cell therapy, in combination with standard-of-care chemotherapy, to safely produce durable responses in patients with advanced pancreatic cancer. In this study, a number of patient responses occurred after the period in which a chemotherapy-driven response would typically occur, suggesting MultiTAA’s potential to produce added benefit in this patient population. Additionally, we also observed induction of the endogenous immune system – or epitope spreading – suggesting that the benefits of MultiTAA may extend beyond the targeted antigens and further contribute to a long-lasting anti-tumor effect."

Presentation Title:

"A phase I trial targeting advanced or metastatic pancreatic cancer using a combination of standard chemotherapy and adoptively transferred nonengineered, multiantigen specific T cells in the first-line setting (TACTOPS)"

Study Design:

Arm A is evaluating the safety and potential efficacy of using MultiTAA-specific T cells in the first-line setting for chemo-responsive patients with pancreatic adenocarcinoma. Patients in Arm A receive at least three months of standard-of-care chemotherapy (gemcitabine/nab-paclitaxel or FOLFIRINOX) – the period during which a response to chemotherapy would typically occur – before receiving up to six administrations of MultiTAA-specific T cells in conjunction with chemotherapy.

Summary of Interim Results

Between June 2018 and December 2019, 13 patients have been treated, each of whom received up to 6 monthly infusions of 1×107 MultiTAA-specific T cells/m2 in conjunction with ongoing first-line chemotherapy and without prior protocol-associated lymphodepletion. For 12 of the 13 patients, sufficient cells for all six planned doses were generated; two doses were available for the remaining patient.

·Out of the 13 evaluable patients (best overall response):

o4 patients experienced objective responses after administration of MultiTAA cells;

§1 patient experienced a radiographic complete response occurring at month 9 after starting chemotherapy;

§3 patients experienced partial responses per RECIST occurring at 6-9 months after starting chemotherapy;

o6 patients experienced stable disease;

o1 patient experienced a mixed response (some lesions increased in size and others decreased for a net zero change in size of tumor lesions);

o2 patients experienced disease progression;

·For 9 of the 13 patients, the cancer was controlled for a period longer than historical controls relative to the type of chemotherapy used
·5 patients enrolled in the study were not administered MultiTAA-specific T cells, either because of disease progression (4 patients) which made them ineligible for treatment, or because insufficient starting material from the patient was available for manufacturing (1 patient);
·Evidence of epitope-spreading was observed in all responders, suggesting that the MultiTAA T cell therapy triggered the recruitment of a broader endogenous immune system response for improved anti-tumor activity;
·No infusion-related reactions, cytokine release syndrome or neurotoxicity was observed.

Mythili Koneru, M.D., Ph.D., Chief Medical Officer of Marker Therapeutics commented: "We are pleased with these interim results, which demonstrate the potential of our therapy to simultaneously recognize and target multiple antigens. As the tumor microenvironment varies from patient to patient, the ability to address these differences may offer a significant benefit to patients. While these results represent a small patient population, we look forward to generating additional data that may support MultiTAA’s future development in this challenging disease area."

The TACTOPS poster and corresponding recorded presentation by Dr. Smaglo will be available on demand through the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program on the ASCO (Free ASCO Whitepaper) website beginning on May 29, 2020, at 8:00 a.m. EDT.

Conference Call and Webcast
Marker will host a conference call and webcast on Monday, June 1st at 8:00 am EDT featuring Dr. Brandon Smaglo, as well as Marker senior management, to discuss the data. The webcast will be accessible in the Investors section of the Company’s website at markertherapeutics.com. Individuals can participate in the conference call by dialing 877-407-8913 (domestic) or 201-689-8201 (international).

The archived webcast will be available for replay on the Marker website following the event.

About MultiTAA-Specific T Cell Therapy

Marker’s Multi-Antigen Targeted (MultiTAA) platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s blood capable of recognizing a broad range of tumor antigens. In early clinical trials, the multi-antigen approach has been well tolerated and shown to enhance tumor destroying capability and is one of the first therapies to consistently demonstrate epitope spreading – inducing the patient’s own T cells to expand, potentially contributing to a lasting anti-tumor effect. Unlike other cell therapies which require pre-conditioning regimens and hospitalization, MultiTAA is designed to be administered in an outpatient setting.

On May 29, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX), reported the final results from the GENUINE Phase 3 study evaluating the combination of ublituximab, the Company’s novel glycoengineered anti-CD20 monoclonal antibody, plus ibrutinib compared to ibrutinib alone in patients with previously treated high-risk chronic lymphocytic leukemia (CLL) at the 56thAmerican Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, TG Therapeutics, MAY 29, 2020, View Source [SID1234558738]).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "We are extremely pleased with the final results of the GENUINE Phase 3 trial presented today. Not only is this the first randomized trial to show a PFS benefit with the addition of an anti-CD20 antibody to ibrutinib, compared to ibrutinib monotherapy, it was also highly encouraging to see the combination significantly improved overall response rate, complete response rate, and importantly increased the rates of undetectable minimal residual disease." Mr. Weiss continued, "We believe these data support the potential of combination therapies to improve outcomes for patients with high risk CLL, especially those with 17p deletion/TP53 mutation, who continue to progress more rapidly than those without high risk cytogenetics."

Details of the data presentation are included below.

Presentation Title: Effect of Adding Ublituximab to Ibrutinib on PFS, ORR, and MRD Negativity in Previously Treated High-Risk Chronic Lymphocytic Leukemia: Final Results of the GENUINE Phase III Study

The GENUINE trial is an open-label, multicenter, randomized, Phase III study in relapsed or refractory high-risk CLL (del17p, del11q, or TP53mutation). This presentation includes data from 117 patients treated with either ublituximab plus ibrutinib (n=59) or ibrutinib alone (n=58). As of the cut-off date of September 1, 2019, patients had a median follow-up time of 41.9 months. The primary endpoint for this trial was overall response rate (ORR) as determined by an independent review committee (IRC). The secondary endpoints included progression free survival (PFS) and complete response (CR) rate as determined by an IRC, and undetectable minimal residual disease (uMRD) assessed by central lab.

Efficacy and safety highlights include:

The addition of ublituximab to ibrutinib compared to ibrutinib monotherapy significantly improved ORR (93% compared to 78%; p=0.019), complete response/complete response with incomplete blood count recovery (CR/CRi) rate (20% vs. 5%; p=0.024), and increased rates of uMRD (46% vs. 7%; p<0.001) in patients with relapsed/refractory CLL with high-risk cytogenetics
At a median follow-up of 41.9 months, median PFS was not reached in the ublituximab plus ibrutinib arm and was 35.9 months in the ibrutinib monotherapy arm (hazard ratio 0.46), with del17p/TP53mut patients seeing the greatest difference in PFS
The addition of ublituximab to ibrutinib did not significantly alter the known safety profile of ibrutinib however the combination resulted in slightly higher rates of neutropenia (36% compared to 21%) and atrial fibrillation (14% compared to 7%)
The data presented is available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

ABOUT THE GENUINE PHASE 3 STUDY
The GENUINE Phase 3 study is a randomized, open label, multicenter clinical trial to evaluate the safety and efficacy of ublituximab plus ibrutinib compared to ibrutinib alone in adult patients with high-risk chronic lymphocytic leukemia (CLL) who received at least one prior therapy for their disease.

Patients received ibrutinib orally at 420 mg once daily in both arms and in the combination arm those patients also received intravenous infusions of ublituximab at 900 mg dosed on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6. Patients in the combination arm who had not progressed received quarterly infusions of ublituximab maintenance at 900 mg.

On May 29, 2020 Rakuten Medical, Inc. (Rakuten Medical), a global biotechnology company developing precision, cell-targeting investigational therapies on its Illuminox technology platform, reported that established a strategic cancer research alliance network, the Illuminox Alliance Institutes (IAI), in order to advance the development of new cancer therapies (Press release, Rakuten Medical, MAY 29, 2020, View Source [SID1234558737]). The National Cancer Center Japan (NCC) signed a memorandum of understanding (MOU) to become the first institution to join the IAI network. Rakuten Medical will expand the IAI network to include premier cancer centers from around the world.

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NCC is currently conducting clinical trials with ASP-1929, Rakuten Medical’s first investigational drug developed on the Illuminox platform. Under the signed MOU, NCC and Rakuten Medical will pursue multiple avenues to advance Illuminox-based cancer therapies. NCC will designate a lead principal who will act as an Illuminox Advisor. The Illuminox Advisor will, based on their expertise, actively participate in various research plans and Advisory board meetings, support identification of additional investigators from the IAI and assist with education and training related to the use of Illuminox platform therapies.

Hiroshi Mikitani, Chairman and CEO of Rakuten Medical, remarked, "There are no international borders in the mission to conquer cancer. Through the Illuminox Alliance, we attempt to advance novel cancer therapies with speed and agility to provide options to patients in need."

On May 29, 2020 Creatv MicroTech, a privately-held biotechnology company reported that it has pioneered a blood test for the universal screening of early stage cancer (Press release, CREATV MICROTECH, MAY 29, 2020, View Source [SID1234558736]). They will present their initial clinical data showing the ability to identify invasive cancer with 87% accuracy. "We are delighted to present results from a training set of 10 different types of cancers," said Dr. Cha-Mei Tang, Chief Executive Officer of Creatv. "The data shows that we obtained 85% sensitivity for all cancers (from 79% of patients in Stage I and increasing to 95% of patients in Stage IV), and also shows 100% specificity when tested against healthy normal controls. This represents a significant step towards pan cancer screening by a routine blood draw with high sensitivity and specificity."

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Creatv’s poster, Circulating Stromal Cells as a Blood Based Biomarker for Screening Invasive Solid Tumors, Abstract ID: 3535, highlights the performance of the LifeTracDxTM blood test. In a completely novel concept, the test analyzed the patient’s immune response to the presence of cancer by isolating stromal cells originating from cancer sites that have migrated into the blood stream. Creatv has shown that a particular subtype of circulating stromal cell, named Cancer Associated Macrophage-Like cells (CAMLs), can be used to identify patients with cancer but are absent in healthy persons. CAMLs are phagocytic myeloid cells derived from the patient’s immunological response to active malignancy that have engorged cancer cells, thereby containing cancer protein markers and cancer DNA.

In a large multi-institutional study, 7.5mL of peripheral blood was taken from 308 cancer patients after a diagnosis of invasive malignancy, [stage I (n=76), stage II (n=73), stage III (n=72), stage IV (n=65) and unstaged non-metastatic (n=22)]. Patients were recruited with lung, pancreas, breast, prostate, esophageal, renal cell, hepatocellular, neuroblastoma, melanoma, and others. To compare specificity of the test, blood was also taken from 39 patients with untreated non-malignant conditions (i.e. benign breast masses, lupus, liver cirrhosis, etc.), and from 76 healthy volunteers. CAMLs were 87% accurate at identifying cancer patients when compared to healthy controls or from patients with non-malignant conditions.

These initial findings have now been granted funding from National Cancer Institute/National Institute of Health (NCI/NIH), Department of Defense and NCI/NIH for validation studies in the screening of 1000 breast patients, 1000 lung patients and 300 prostate patients, respectively.

Posters will be available online at View Source

About LifeTracDxTM Blood Test

Creatv’s liquid biopsy assays (LifeTracDxTM) are commercialized research use only tests designed for analysis of CAMLs and Circulating Tumor Cells (CTCs) from whole blood. LifeTracDxTM tests are applicable for cancer screening, companion diagnostics, prediction of treatment response including immunotherapy, providing prognosis, delivering purified tumor DNA for sequencing, detecting minimal residual disease and early detection of cancer recurrence. LifeTracDxTM tests are currently being implemented in more than 20 clinical trials spanning from basic research to drug development. Creatv’s publications have shown that LifeTracDxTM can be used in an array of solid cancers as an early predictor of patient response to therapy.