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Marker Therapeutics Reports Interim Results of its MultiTAA-Specific T Cell Therapy in Patients with Pancreatic Adenocarcinoma at the 2020 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting

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.

TG Therapeutics Announces Final Results of the GENUINE Phase 3 Study Evaluating Ublituximab plus Ibrutinib in Previously Treated High-Risk Chronic Lymphocytic Leukemia at the 56th American Society of Clinical Oncology Annual Meeting

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]).

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.

Rakuten Medical Establishes Illuminox™ Alliance Institutes to Accelerate Development of Cancer Therapies, Announcing The National Cancer Center Japan as the First Institute to Join the Alliance

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.

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."

Creatv Announces Positive Results for the LifeTracDx Blood Test in the Detection of Early Stage Cancer in Multiple Solid Tumors

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."

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.

Nanobiotix Announces Positive First Results From Phase I Expansion in Locally Advanced Head and Neck Cancer at ASCO 2020

On May 29, 2020 NANOBIOTIX (Paris:NANO)(Euronext: NANO – ISIN: FR0011341205 – the "Company"), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported new data from the expansion part of its phase I trial, evaluating the potential of first-in-class NBTXR3 activated by radiation therapy to improve treatment outcomes for elderly patients with locally advanced head and neck cancer ineligible for chemotherapy or intolerant to cetuximab (Press release, Nanobiotix, MAY 29, 2020, View Source [SID1234558735]). The data were published as part of the virtual scientific program at the 2020 annual meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper).

Study 102: A phase I trial of hafnium oxide nanoparticles activated by radiotherapy in cisplatin-ineligible locally advanced HNSCC patients

Authors: Christophe Le Tourneau, Valentin Calugaru, Edith Borcoman, Victor Moreno, Emiliano Calvo, Xavier Liem, Sebastien Salas, Bernard Doger, Olivier Choussy, Maria Lesnik, Xavier Mirabel, Nathalie Badois, Samar Krhili, Josefin Blomkvist, Nicolas Fakhry, Stéphanie Wong-Hee-Kam, Caroline Hoffmann.

J Clin Oncol 38: 2020 (suppl; abstr 6573). DOI: 10.1200/JCO.2020.38.15_suppl.6573.

Abstract Number: 6573

Study Design

After reporting promising early signs of activity from the dose escalation part of its phase I trial evaluating the safety and feasibility of NBTXR3 activated by radiation therapy in elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the Company launched an expansion cohort to confirm results and observed trends with a larger population treated at the recommended dose. This part of the study is expected to recruit a total of 44 evaluable patients. To date, 40 patients have been recruited, 30 of whom are evaluable for efficacy and are included in the data presented at ASCO (Free ASCO Whitepaper) 2020.

Topline Results

As previously announced, in the dose escalation part of the study NBTXR3 activated by radiation therapy was safe and well tolerated. The recommended phase 2 dose (RP2D) was determined to be 22% of baseline tumor volume. Among 16 evaluable patients, injected lesion complete response rate was 56% and overall objective response rate was 69%.

Regarding the new, expansion part data, analysis of 40 patients dosed showed that NBTXR3 activated by radiation therapy remains safe and well tolerated. In terms of efficacy, for the 30 evaluable patients, investigators observed, at a median time of 5 months after NBTXR3 injection, an overall objective response rate of 83% and an overall complete response rate of 43% and objective response rate of the primary tumor (target lesion) of 83% with a complete response rate of the primary tumor of 60%. The safety profile was consistent with the dose escalation part and the efficacy data improved (i.e. an increase in overall objective response rate from 69% in the dose escalation part to 83% in the dose expansion part).

In the safety population (all treated patients, N=40), three serious adverse events (SAEs) related to NBTXR3 were observed (0.7% of all AEs), comprising one case each of: Grade 4 tumor hemorrhage also related to radiotherapy, Grade 3 mucosal inflammation and Grade 2 swollen tongue also related to the injection procedure. Two SAEs related to the injection procedure were reported (0.5% of all AEs), comprising: two cases of swollen tongue, of which one was Grade 2 and also related to NBTXR3, and one was Grade 4. The radiotherapy-associated safety profile was as expected with the most frequently occurring AEs being stomatitis and skin injury. Three deaths due to AEs related to radiotherapy and other causes were observed. Four other patients died of non-oncologic or non-toxicity-related reasons.

Next Steps in Head and Neck Cancer

The expansion part of the phase I trial will continue to recruit until reaching 44 evaluable patients. In parallel, subject to the FDA’s pending review, the Company intends to globally launch a pivotal phase III trial. In the planned phase III trial, a futility analysis is expected 18 months after the first patient is randomized, and an interim analysis of progression-free survival (PFS) is expected at 24-30 months.

NBTXR3 for the treatment of locally advanced HNSCC patients who are not eligible for platinum-based chemotherapy received Fast Track designation from the FDA in February 2020. Fast Track designation is a process designed to facilitate the development and accelerate the review of drugs for serious conditions that have the potential to address unmet medical needs. The purpose is to expedite the availability of new treatment options for patients.

About NBTXR3

NBTXR3 is a first-in-class product designed to destroy tumors through physical cell death when activated by radiotherapy. NBTXR3 has a high degree of biocompatibility, requires one single administration before the first radiotherapy treatment session, and has the ability to fit into current worldwide radiation therapy standards of care. The physical mode of action of NBTXR3 makes it applicable across solid tumors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) of the oral cavity or oropharynx in elderly patients unable to receive chemotherapy or cetuximab with limited therapeutic options. Promising results have been observed in the phase I trial regarding local control. In the United States, the Company has started the regulatory process to commence a phase III clinical trial in locally advanced head and neck cancers.

Nanobiotix is also running an Immuno-Oncology development program. The Company has launched a Phase I clinical trial of NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors in locoregional recurrent (LRR) or recurrent and metastatic (R/M) HNSCC amenable to re-irradiation of the HN and lung or liver metastases (mets) from any primary cancer eligible for anti-PD-1 therapy.

Other ongoing NBTXR3 trials are treating patients with hepatocellular carcinoma (HCC) or liver metastases, locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and pancreatic cancer. The Company has a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center (initially expected to support 9 new clinical trials in the United States) to evaluate NBTXR3 across several cancer types.