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).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

On May 27, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported that it has been selected as the winner of the "Best New Technology Solution – Dermatology" award in the sixth annual MedTech Breakthrough Awards program for its innovative DecisionDx-Melanoma gene expression profile (GEP) test (Press release, Castle Biosciences, MAY 27, 2022, View Source [SID1234615204]). DecisionDx-Melanoma leverages Castle’s advanced technologies to identify the risk of metastasis, recurrence and sentinel lymph node (SLN) positivity for patients diagnosed with invasive cutaneous melanoma. In 2021, Castle was awarded "Best New Technology Solution – Oncology" by MedTech Breakthrough for its DecisionDx-SCC and DecisionDx DiffDx-Melanoma GEP tests, both of which were launched in the second half of 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The mission of the MedTech Breakthrough Awards is to honor excellence and recognize the innovation, hard work and success in a range of health and medical technology categories. This year’s program attracted more than 3,900 nominations from over 15 different countries throughout the world.

DecisionDx-Melanoma is Castle’s proprietary risk stratification GEP test that is designed to use a patient’s tumor biology to predict individual risk of metastasis or recurrence for patients diagnosed with invasive cutaneous melanoma, a deadly skin cancer, as well as the risk of SLN positivity, independent of traditional staging factors. Unlike traditional treatment plans that are developed using clinical and pathologic factors alone (e.g., a patient’s age, tumor thickness, ulceration, etc.), incorporating the patient’s primary tissue biology can help physicians and patients make more informed disease management decisions aligned with each patient’s unique biologic risk.

"Having an accurate picture of whether melanoma is likely to recur or spread is critical to making the right treatment and disease management decisions, and though risk indicators like clinicopathological factors and patient history are important, they have their limitations," said James Johnson, managing director, MedTech Breakthrough. "Genomic testing can supplement these traditional factors, and Castle’s GEP test has been shown to accurately and independently predict individual risk of recurrence or metastasis, and can provide clinically actionable and personalized information to inform the treatment plan for each patient. Congratulations to the Castle team for being our choice for ‘Best New Technology Solution – Dermatology.’"

In 2021, Castle incorporated two new proprietary, independently validated algorithms into its DecisionDx-Melanoma test: i31-SLNB (designed to predict SLN positivity) and i31-ROR (designed to predict an individual patient’s risk of recurrence). These algorithms combine a patient’s clinical and pathologic risk factors with their DecisionDx-Melanoma class result to provide an Integrated Test Result with precise and personalized risk information specific to each patient, including his/her:

Personalized likelihood of SLN positivity, thus informing consideration of the SLN biopsy surgical procedure.
Personalized, patient-specific risk of recurrence predictions, including five-year outcomes for melanoma-specific survival, distant metastasis-free survival and recurrence-free survival, to give guidance for patient follow-up and treatment intensity decisions.
"The choices that clinicians and patients make immediately after a diagnosis of invasive melanoma can be critical and ultimately determine the outcome of a patient’s disease," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "Thus, it was important to us at Castle that our DecisionDx-Melanoma test provided the most precise and personalized information possible to help inform potentially life-changing decisions around the management and treatment of a patient’s cancer. We are thrilled to win this award, recognizing our innovative DecisionDx-Melanoma test that we believe is transforming the management of melanoma and guiding improved patient care."

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma (CM) metastasis or recurrence, as well as the risk of sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 6,300 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. Additionally, Castle has an ongoing collaboration with the National Cancer Institute (NCI) to link DecisionDx-Melanoma testing data with data from the Surveillance, Epidemiology and End Results (SEER) Program’s registries on CM cases. This collaboration has resulted in Castle’s analysis of 5,226 samples (clinically tested through December 31, 2018) in a study to evaluate melanoma-specific survival and overall survival; in this study, patients tested with DecisionDx-Melanoma had better survival rates than untested patients, and the data suggested that DecisionDx-Melanoma can accurately risk-stratify for disease progression to aid in risk-aligned treatment plans for improved patient outcomes and survival. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Additionally, impact on patient management plans for one of every two patients tested has been shown in five multi-center/single-center studies including more than 800 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an Integrated Test Result. Through March 31, 2022, DecisionDx-Melanoma has been ordered 97,288 times for patients with cutaneous melanoma.

On May 27, 2022 Enterome, a clinical stage biopharmaceutical company developing first-in-class immunomodulatory drugs based on its bacterial Mimicry drug discovery platform, reported the publication of three abstracts related to its OncoMimcs pipeline, including EO2401, its first-in-class off-the-shelf OncoMimics cancer immunotherapy, ahead of poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 3-7, 2022 in Chicago and virtually (Press release, Enterome, MAY 27, 2022, View Source [SID1234615168]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Enterome will present clinical proof-of-concept data from its most advanced OncoMimics drug candidate, EO2401, a therapeutic cancer vaccine candidate currently in clinical development for the treatment of patients with first progression/recurrence of glioblastoma (ROSALIE trial, EOGBM1-18) and for the treatment of patients with locally advanced or metastatic adrenocortical carcinoma, or malignant pheochromocytoma/paraganglioma (SPENCER trial, EOADR1-19).

A third poster describing the Phase 1/2 trial (SIDNEY, EONHL1-20) with Enterome’s second OncoMimics vaccine, EO2463, in non-Hodgkin lymphoma will also be presented at ASCO (Free ASCO Whitepaper).

Details of the poster presentations and session are as follows:

ROSALIE Trial (EOGBM1-18)

Title: EO2401, a novel microbiome-derived therapeutic vaccine for patients with recurrent glioblastoma
Track: Central Nervous System Tumors
Abstract number: #2034
Date and Time: Sunday, June 5, 8:00 AM-11:00 AM CDT
Presenter: Professor Wolfgang Wick, Universitätsklinikum Heidelberg and German Cancer Research Center, Heidelberg, Germany
Authors: Wick, W. et al
SPENCER Trial (EOADR1-19)

Title: EO2401, a novel microbiome-derived therapeutic vaccine for patients with adrenocortical carcinoma (ACC)
Track: Genitourinary Cancer—Kidney and Bladder
Abstract number: #4596
Date and Time: Saturday, June 4, 1:15 PM-4:15 PM CDT
Presenter: Professor Vivek Subbiah, The University of Texas MD Anderson Cancer Center (MDACC), Houston, TX
Authors: Baudin, E. et al
SIDNEY Trial (EONHL1-20)

Title: A novel microbial-derived peptide therapeutic vaccine (EO2463) as monotherapy and in combination with lenalidomide and rituximab, for treatment of patients with indolent non-Hodgkin lymphoma
Poster session: Hematologic Malignancies/Lymphoma and Chronic Lymphocytic Leukemia
Poster number: #TPS7586
Date and Time: Saturday, June 4, 8:00 -11:00 AM CDT
Authors: Zinzani, P.L et al

About OncoMimics Peptides

OncoMimics peptides are gut microbiome-derived peptides that closely mimic antigens expressed by tumor cells. In contrast to tumor antigens, however, OncoMimics peptides are recognized by the immune system as "non-self" and can generate a strong human cytotoxic CD8+ response steming from memory T cells, offering enormous potential to create a new class of cancer vaccines targeting solid and liquid tumors.

Enterome’s pioneering work on its OncoMimics pipeline leverages the fundamental understanding that the gut is the largest lymphoid organ in the body and is home to most of its memory T-cells. As a result, there is constant interaction and presentation of peptides and proteins secreted by gut bacteria to the body’s immune system, resulting in the formation of a pool of effector memory T cells protecting the human body against bacterial invasion. In the event that the bacterial antigens are mimics of tumor antigens, this process leads to the generation of circulating effector memory T cells with a preserved ability to recognize tumor antigens.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing next-generation multifunctional biotherapeutics, reported that management will participate in an upcoming investor conference (Press release, Zymeworks, MAY 27, 2022, View Source [SID1234615205]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Jefferies Healthcare Conference. Zymeworks will participate in one-on-one meetings on June 8th – 9th and will present on June 8th at 9:30 a.m. ET in New York, NY.
The presentation will be available on Zymeworks’ website at View Source