On May 27, 2022 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported that the VAL-083 treatment arm in the Global Coalition for Adaptive Research (GCAR) registrational Phase 2/3 clinical trial for glioblastoma (GBM), titled Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE), has activated its first European site, University Hospital Zurich in Zurich, Switzerland (Press release, Kintara Therapeutics, MAY 27, 2022, View Source [SID1234615199]).

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GBM AGILE is currently active at 44 clinical sites in the United States and Canada as of May 26, 2022.

GBM AGILE is a patient-centered, Phase 2/3 adaptive platform trial evaluating multiple therapies for patients with newly-diagnosed and recurrent GBM. Since January 2021, GCAR has accelerated the pace of clinical site activation with increased awareness in the medical community of Kintara’s arm of the study. GCAR plans to enroll 150-200 patients in the Kintara arm of the study at over 40 sites in the U.S. and Canada with potential to increase this total to 65 clinical trial centers worldwide.

"This first European clinical site for the Kintara treatment arm of the GBM AGILE study joins 44 active sites in the U.S. and Canada," stated Timothy Cloughesy, M.D., Global Principal Investigator for the GBM AGILE study and Professor of the Neurology and Molecular and Medical Pharmacology program at the University of California, Los Angeles. "We are pleased with the reception we are receiving internationally, and this milestone provides us with continued confidence in the ability of GCAR’s GBM AGILE platform trial to materially accelerate the clinical development timelines for companies."

"We continue to see an accelerated pace for which our treatment arm is being executed in the study," commented Robert E. Hoffman, Kintara’s President and Chief Executive Officer. "We are also observing GCAR’s exceptional clinical trial execution capabilities, which were among the aspects that drew us to participate in this highly efficient registrational study. This achievement provides continued excitement as this study progresses."

GBM AGILE is an international, innovative platform trial designed to more rapidly identify and confirm effective therapies for patients with GBM through response adaptive randomization and a seamless Phase 2/3 design. The trial, conceived by over 130 key opinion leaders, is conducted under a master protocol allowing multiple therapies, or combinations of therapies, from different pharmaceutical partners to be evaluated simultaneously. With its innovative design and efficient operational infrastructure, data from GBM AGILE may be used as the foundation for a new drug application and biologics license application submissions and registrations to the FDA and other health authorities.

On May 27, 2022 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that management will be attending the Jefferies Healthcare Conference at the Marriott Marquis in New York City (Press release, Autolus, MAY 27, 2022, View Source [SID1234615198]). Autolus’ Chief Executive Officer Dr. Christian Itin will participate in a Fireside Chat on Thursday, June 9 at 9.00 – 9.30 am ET (2:00 pm – 2.30 pm BST) and the Company will also be attending one-on-one investor meetings at the event.

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An audio webcast of the Fireside Chat will be on the Events section of the Autolus website. An archived version will also be available through the Company’s website for a limited time following the conference.

On May 27, 2022 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported that an abstract reporting preliminary data from the two Phase I trials assessing TG4050, its individualized neoantigen cancer vaccine, has been selected for a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, Transgene, MAY 27, 2022, View Source [SID1234615197]). The conference will be held online and in-person in Chicago, IL, USA, from June 3 to 7, 2022.

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The abstract reports positive immunogenicity and clinical data generated from the two ongoing Phase I trials in patients with ovarian cancer and HPV-negative head and neck cancer (NCT03839524 and NCT04183166). The detailed data will be presented during a poster session on June 5, 2022, at the ASCO (Free ASCO Whitepaper) conference.

Poster title: Phase 1 studies of personalized neoantigen vaccine TG4050 in ovarian carcinoma (OC) and head and neck carcinoma (HNSCC)

Abstract number: 2637
Session title: Developmental Therapeutics—Immunotherapy
Session date and time: Sunday, June 5, 2022, 8:00 am-11:00 am CDT

Authors: J.P. Delord, M. Block, C. Ottensmeier, G. Colon-Otero, C. Le Tourneau, A. Lalanne, O. Lantz, KL. Knutson, G. Lacoste, A. Tavernaro, M. Brandely, N. Silvestre, B. Grellier, Y. Yamashita, O. Kousuke, N. Yamagata, Y. Tanaka, B. Malone, E. Quemeneur, K. Bendjama

The abstract can be accessed on the ASCO (Free ASCO Whitepaper) and Transgene websites.

About the clinical trials

TG4050 is being evaluated in two Phase I clinical trials for patients with ovarian cancer (NCT03839524) and HPV-negative head and neck cancers (NCT04183166).

In a first Phase I trial, TG4050 is being administered to patients with HPV-negative head and neck cancer. A personalized treatment is created for each patient after they complete surgery and while they receive an adjuvant therapy. Half of the participants receive their vaccine immediately after they complete their adjuvant treatment. The other half is given TG4050 as an additional treatment at the time of recurrence of the disease. This randomized study is evaluating the treatment benefits of TG4050 in patients who have a high risk of relapse. Up to 30 patients will receive TG4050 in France, in the UK and in the USA. The principal investigator of the trial is Prof. Christian Ottensmeier, MD, PhD, Consultant Medical Oncologist at the Clatterbridge Cancer Centre and Professor of Immuno-Oncology at the University of Liverpool. In France, the clinical trial is being conducted at Institut Curie, Paris by Prof. Christophe Le Tourneau, MD, PhD, Head of the Department of Drug Development and Innovation (D3i), and at the IUCT-Oncopole, Toulouse by Prof. Jean-Pierre Delord. In the USA, the trial is being led by Dr. Yujie Zhao, MD, PhD, at the Mayo Clinic. Endpoints of the trial include safety, feasibility and biological activity of the therapeutic vaccine.

In parallel, a Phase I clinical trial of TG4050 is enrolling patients with ovarian cancer. This second trial is including patients at the time of asymptomatic relapse after surgery and first-line chemotherapy. Dr. Matthew Block, MD, PhD, Consultant Medical Oncology, Consultant Immunology and Associate Professor of Oncology at the Mayo Clinic (USA) is the principal investigator of the trial; in France, the trial is being conducted by Prof. Le Tourneau, MD, PhD, at Institut Curie and by Dr. Alexandra Martinez, MD, Associate Head of Surgical Department, at IUCT-Oncopole. Endpoints of the trial include safety, feasibility and biological activity of the therapeutic vaccine.

The first preliminary clinical data generated from the first patients treated with TG4050 were very encouraging.

About myvac

myvac is a viral vector (MVA – Modified Vaccinia Ankara) based, individualized immunotherapy platform that has been developed by Transgene to target solid tumors. myvac-derived products are designed to stimulate the patient’s immune system, recognize and destroy tumors using the patient’s own cancer specific genetic mutations. Transgene has set up an innovative network that combines bioengineering, digital transformation, established vectorization know-how and unique manufacturing capabilities. Transgene has been awarded "Investment for the Future" funding from Bpifrance for the development of its platform myvac. TG4050 is the first myvac-derived product being evaluated in clinical trials.

Click here to watch a short video on myvac.

About TG4050

TG4050 is an individualized immunotherapy being developed for solid tumors that is based on Transgene’s myvac technology and powered by NEC’s longstanding artificial intelligence (AI) expertise. This virus-based therapeutic vaccine encodes neoantigens (patient-specific mutations) identified and selected by NEC’s Neoantigen Prediction System. The prediction system is based on more than two decades of expertise in AI and has been trained on proprietary data allowing it to accurately prioritize and select the most immunogenic sequences.

TG4050 is designed to stimulate the immune system of patients in order to induce a T-cell response that is able to recognize and destroy tumor cells based on their own neoantigens. This individualized immunotherapy is developed and produced for each patient.

On May 27, 2022 Exact Sciences Corp. (NASDAQ: EXAS), a leader in advanced cancer diagnostics, reported new data supporting its cancer tests and treatment guidance tools will be showcased in nine poster presentations and five e-abstracts at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held June 3-7 in Chicago, Illinois (Press release, Exact Sciences, MAY 27, 2022, View Source [SID1234615186]).

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"As the leading cause of death worldwide,1 cancer creates tremendous human suffering and staggering health care costs. Tests to help catch the disease earlier and guide more effective treatment are necessary to improve outcomes," said Kevin Conroy, chairman and CEO of Exact Sciences. "Together with our collaborators from leading medical institutions, Exact Sciences is proud to present extensive data at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting. These presentations highlight the breadth of our pipeline and portfolio of tests as part of our relentless efforts to advance the field of cancer diagnostics."

Studies supporting Exact Sciences’ screening and earlier detection efforts include a comparison of simulated outcomes between stool- and blood-based colorectal cancer screening tests. The modeled outcomes suggest blood-based tests result in detecting fewer colorectal cancer cases compared to stool-based tests due to differences in colorectal cancer sensitivity and specificity and lower advanced adenoma detection rates.2 A cost-effectiveness analysis that assumed adherence to stool-based screening and/or follow-up colonoscopy increased when coinsurance was waived showed improvement in outcomes including life years gained and CRC incidence and mortality reductions.3 Another study indicated a shorter time to diagnosis for screenable versus symptom-driven cancers, supporting an expanded use of multi-cancer testing.4

Also being presented are findings from Mayo Clinic as part of the academic center’s ongoing collaboration with Exact Sciences to advance the use of methylated DNA markers in detecting a range of cancer types, including cutaneous melanoma, prostate cancer, and lymphoma.5

Data highlighting Exact Sciences’ precision oncology portfolio of tests will also be presented. The analyses support use of Oncomap and Oncomap ExTra, comprehensive genomic profiling tests formerly known as the Oncotype Map Pan-Cancer Tissue and GEM ExTra tests, respectively, to inform targeted therapy selection and clinical trial options for patients with advanced solid tumors.6 Also being presented is an overview of the ongoing CORRECT-MRD II study, designed to generate clinical validation data for the company’s minimal residual disease assay in Stage II and III colorectal cancer patients.7

Following are details for the fourteen abstracts that have been accepted at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting. All abstracts are now available in the ASCO (Free ASCO Whitepaper) Meeting Library.

Saturday, June 4

NSABP C-14: CORRECT-MRD II – Second colorectal cancer clinical validation study to predict recurrence using a circulating tumor DNA assay to detect minimal residual disease
Authors: Salem, M., et al.
Session: Gastrointestinal Cancer ‒ Colorectal and Anal
Poster Discussion: 8:00-11:00 a.m. CT
Abstract Number: TPS3632

Methylated DNA markers in early detection of lymphoma: Discovery, validation, and clinical pilot
Authors: Witzig, T., et al.
Session: Hematologic Malignancies ‒ Lymphoma and Chronic Lymphocytic Leukemia
Poster Discussion: 8:00-11:00 a.m. CT
Abstract Number: 7562

Sunday, June 5

Comprehensive genomic profiling to identify gene alterations in DNA repair pathway across solid tumors
Authors: McDonnell, K., et al.
Session: Developmental Therapeutics ‒ Molecularly Targeted Agents and Tumor Biology
Poster Discussion: 8:00-11:00 a.m. CT
Abstract Number: 3124

Monday, June 6

Comprehensive whole-exome and transcriptome profiling to identify actionable alterations associated with response to PARP inhibitors in breast cancer
Authors: Dombrowski, S., et al.
Session: Breast Cancer ‒ Metastatic
Poster Discussion: 8:00-11:00 a.m. CT
Abstract Number: 1096

BRAF mutation classes and co-occurring mutations in NSCLC
Authors: Niu, J., et al.
Session: Lung Cancer ‒ Non-Small Cell Metastatic
Poster Discussion: 8:00-11:00 a.m. CT
Abstract Number: 9083

Characterization of time to diagnosis indicates shorter interval for screenable versus symptom-driven cancers
Authors: Gainullin, V., et al.
Session: Prevention, Risk Reduction, and Hereditary Cancer
Poster Discussion: 1:15-4:15 p.m. CT
Abstract Number: 10526

Comparison of simulated outcomes between stool- and blood-based colorectal cancer screening tests
Authors: Fendrick, A. M., et al.
Session: Prevention, Risk Reduction, and Hereditary Cancer
Poster Discussion: 1:15-4:15 p.m. CT
Abstract Number: 10529

Plasma methylated DNA markers of cutaneous melanoma: Association with PET/CT-positive disease
Authors: Meves, A., et al.
Session: Melanoma/Skin Cancers
Poster Discussion: 3:15-6:15 p.m. CT
Abstract Number: 9567

Methylated DNA markers in urine aid in the selective identification of patients with prostate cancer as well as clinically significant pathology
Authors: Shah, P., et al.
Session: Genitourinary Cancer ‒ Prostate, Testicular, and Penile
Poster Discussion: 3:15-6:15 p.m. CT
Abstract Number: 5091

Online Publications

Cost-effectiveness of mt-sDNA vs mailed FIT outreach for Medicare Advantage enrollees using the CRC-AIM microsimulation model
Authors: Bhatt, J., et al.
Abstract Number: e18827

Cost-effectiveness of waiving coinsurance for follow-up colonoscopy after a positive stool-based colorectal screening test in a Medicare population
Authors: Fendrick, A. M., et al.
Abstract Number: e13624

Modeling analysis of COVID 19-related delays in colorectal cancer screening on simulated clinical outcomes
Authors: Wilson, L., et al.
Abstract Number: e13631

Plasma methylated DNA markers detect recurrence and response to therapy in colorectal cancer
Authors: Zhu, M., et al.
Abstract Number: e15567

On May 27, 2022 INOVIO (NASDAQ: INO) reported that results from the company’s novel Phase 1/2 trial of INO-5401 and INO-9012 in combination with PD-1 inhibitor Libtayo (cemiplimab) in the treatment of newly diagnosed glioblastoma (GBM), including encouraging median overall survival (OS) data from fifty-two subjects. Median OS duration in unmethylated MGMT (Cohort A) was 17.9 months (Press release, Inovio, MAY 27, 2022, View Source;INO-9012-in-Combination-with-Libtayo-cemiplimab-in-Patients-with-Newly-Diagnosed-GBM-at-ASCO-Annual-Meeting-2022/default.aspx [SID1234615185]). Median OS data in MGMT Methylated patients (Cohort B) are being presented for the first time, at a median of 32.5 months, which compares favorably to historical comparisons (23.2-25 months).

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Overall, INO-5401 + INO-9012 is demonstrated to be tolerable and immunogenic when administered with Libtayo and RT/TMZ (radiation and temozolomide) to newly diagnosed GBM patients. Notably, INO-5401 elicited antigen-specific T cells that may infiltrate GBM tumors. The data from this study was selected to be presented in an oral presentation by Dr. David Reardon on Monday, June 6, 2022, at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) at the McCormick Place Convention Center in Chicago, Illinois.

Presentation Details: June 6, 2022, 12:42 – 12:54 p.m. CDT
Presenting Author: David A. Reardon
Central Nervous System Tumors Session

Abstract #2004: Intramuscular (IM) INO-5401 + INO-9012 with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma

Fifty-two subjects were enrolled: 32 in Cohort A; 20 in Cohort B (35% women; median age 60 years [range 19-78 years]). The adverse event profile was consistent with known single-agent (INO-5401, INO-9012, EP or Libtayo) events; most events were ≤Grade 2 and no related events were Grade ≥4. Median OS durations in Cohorts A and B were 17.9 months (95% CI 14.5-19.8) and 32.5 months (95% CI 18.4-not reached), respectively. Flow cytometry revealed activated, antigen specific CD4+CD69+PD1+ and CD8+CD69+PD1+ T cells, the latter with lytic potential as defined by presence of perforin and granzyme A. Both subsets exhibited HR < 1.0 and p < 0.05 when accounting for a 0.1% T cell frequency change, translating to a 23% and 28% reduced risk of death at 18 months, respectively.

A post-hoc exploratory analysis showed that gene expression levels of INO-5401 antigens and immune cell markers from pre-treatment tumor tissues were similar between alive and deceased groups; however, the alive group displayed significant differential expression of genes regulating apoptosis, proliferation, and immune responses. Post-treatment tumor tissue displayed altered gene expression for immune-related markers versus pre-treatment tissue, including markers of T cell infiltration, activation, and lytic potential.

Dr. David Reardon, Clinical Director, Center for Neuro-Oncology of Dana-Farber Cancer Institute and coordinating principal investigator of the study said, "GBM remains one of the most aggressive and hard-to-treat cancers. The fact that we have seen this novel combination trial of a T cell generating DNA medicine combined with a PD-1 checkpoint benefit a large percent of trial participants past 32 months is very encouraging. These latest results and continued development are welcoming as it continues to improve upon a standard of care which was defined 17 years ago and remains sub-optimal for our patients with GBM."

Dr. Jeffrey Skolnik, INOVIO’s Senior Vice President, Clinical Development, said, "We, along with our collaborative partner Regeneron, remain encouraged with the progress to date from this novel combination therapy study. As concluded in the abstract, INO-5401 + INO-9012 has an acceptable risk/benefit profile and elicits robust immune responses that may correlate with a potentially enhanced survival when administered with Libtayo and RT/TMZ to newly diagnosed GBM patients. Our goal is to build upon INO-5401’s ability to elicit antigen-specific T cells that can infiltrate GBM tumors and complement the clinically-active profile of Libtayo to a potentially larger study in the future."

INO-5401, INO-9012, Libtayo, and the combination of these products have not been approved or evaluated by any Regulatory Authority worldwide for the treatment of newly diagnosed GBM.

Study Design

The trial was designed to evaluate safety, immunogenicity and efficacy of INO-5401 and INO-9012 in combination with Libtayo, with radiation and chemotherapy, in subjects with newly diagnosed glioblastoma (GBM). This is a Phase 1/2, open-label, multi-center trial conducted in 52 evaluable patients with GBM. There are two cohorts in this trial. Cohort A includes 32 participants with a tumor with an unmethylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter. Cohort B includes 20 participants with a tumor with a MGMT methylated promoter. Both cohorts received INO-5401 and INO-9012 and Libtayo at the same doses and on the same dosing schedule, and both cohorts received radiation and TMZ. For more information of the clinical study, see www.clinicaltrials.gov, identifier NCT03491683.

About INO-5401 and INO-9012

INO-5401 encodes for INOVIO’s SynCon antigens for hTERT, WT1, and PSMA, and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1, and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development. These three antigens were reported to be over-expressed, and often mutated, in a variety of human cancers including glioblastoma, and targeting these antigens may prove efficacious in the treatment of patients with cancer. INO-9012 encodes for IL-12, which is a T cell immune activator.

About Glioblastoma (GBM)

GBM is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, with very few new therapies approved over the last 10 years. The median overall survival for patients receiving standard of care therapy is approximately 15 to 22 months and the median progression-free survival is approximately 7-10 months. In the U.S., the estimated annual incidence of GBM is 11,362 cases or 3.21 cases per 100,000 persons and the median age at diagnosis is 65 years.