On April 9, 2021 Seagen Inc. (Nasdaq: SGEN) and Genmab A/S (Nasdaq: GMAB) reported that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) seeking accelerated approval for tisotumab vedotin (Press release, Seagen, APR 9, 2021, View Source [SID1234577783]). This BLA requests FDA approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of October 10, 2021. Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) directed to tissue factor (TF), a cell-surface protein expressed on multiple solid tumors including cervical cancer, and is associated with tumor growth, angiogenesis, metastasis and poor prognosis.1

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 FDA’s filing of the tisotumab vedotin BLA with Priority Review marks an important step forward for this ADC as a potential treatment for patients with recurrent or metastatic cervical cancer," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "We are collaborating closely with the FDA throughout the review process to make this important therapy available to patients."

"We are pleased that the tisotumab vedotin BLA has been accepted with Priority Review by the FDA as there is an unmet need for effective therapies for women with recurrent or metastatic cervical cancer, who have disease progression on or after chemotherapy," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "This is an important milestone for Genmab as it brings us closer to our goal of bringing differentiated therapies to patients and transforming cancer treatment."

The BLA for tisotumab vedotin was submitted in February 2021. The submission is based on the results of the innovaTV 204 pivotal phase 2 single-arm clinical trial evaluating tisotumab vedotin as monotherapy in patients with previously treated recurrent or metastatic cervical cancer. These data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020.

About Cervical Cancer

Cervical cancer originates in the cells lining the cervix. Over 13,500 women are expected to be diagnosed with invasive cervical cancer in the U.S. in 2020, with approximately 4,200 deaths.2 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying annually; the vast majority of these women being in the developing world.3 Routine medical examinations and human papillomavirus (HPV) vaccines have lowered the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which often recurs or becomes metastatic. Current therapies for previously treated recurrent or metastatic cervical cancer generally result in limited objective response rates of typically less than 15 percent with median overall survival ranging from 6.0 to 9.4 months.4-10

About the innovaTV 204 Trial

The innovaTV 204 trial (also known as GCT1015-04 or innovaTV 204/GOG-3023/ENGOT-cx6) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent or metastatic cervical cancer who were previously treated with doublet chemotherapy with or without bevacizumab. Additionally, patients were eligible if they had received up to two prior lines of therapy in the recurrent or metastatic setting. In the study, 101 patients were treated with tisotumab vedotin at multiple centers in the U.S. and Europe. The primary endpoint of the trial was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by independent central review. Key secondary endpoints included duration of response, progression-free survival, overall survival, safety and tolerability.

The study was conducted by Genmab in collaboration with Seagen, European Network of Gynaecological Oncological Trial Groups (ENGOT) and the Gynecologic Oncology Group (GOG) Foundation. For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About Tisotumab Vedotin

Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab’s fully human monoclonal antibody specific for tissue factor and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing target cell death. In cancer biology, tissue factor is a cell-surface protein and associated with tumor growth, angiogenesis, metastasis and poor prognosis.1 Based on its elevated expression in multiple solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach. Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

Tisotumab vedotin is being evaluated in a global phase 3, randomized clinical trial called innovaTV 301 versus investigator’s choice of chemotherapy in recurrent or metastatic cervical cancer. The primary endpoint is overall survival and secondary endpoints include progression-free survival, duration of response, objective response rate, safety and tolerability. Enrollment is ongoing and the study is intended to support global registrations. In addition, tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in recurrent or metastatic cervical cancer, ovarian cancer, and other solid tumors and in combination with commonly used therapies in recurrent or metastatic cervical cancer. These trials are evaluating tisotumab vedotin on a weekly or every three-week dosing schedule. More information about the innovaTV 301 clinical trial, including enrolling sites, as well as other ongoing clinical trials is available at www.clinicaltrials.gov.

On April 9, 2021 Oasmia Pharmaceutical AB, an innovation-focused specialty pharmaceutical company, reported that it will host a conference call on April 12 at 14:00 CEST to present final Cantrixil Phase 1 data set to be released at the 2021 AACR (Free AACR Whitepaper) annual meeting (Press release, Oasmia, APR 9, 2021, View Source [SID1234577782]).

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 call will be hosted by CEO Francois Martelet and CSO Reinhard Koenig. The presentation will be in English.

On April 9, 2021 AstraZeneca reported that it will share updates from the Company’s innovative early oncology pipeline across multiple strategic platforms during the virtual American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, 10 to 15 April 2021 (Press release, AstraZeneca, APR 9, 2021, View Source [SID1234577781]).

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!

Five presentations will unveil the next-generation PARP1 selective inhibitor AZD5305, underscoring AstraZeneca’s commitment to advancing therapies that selectively kill cancer cells by targeting the system that cells rely on to repair damage to DNA. Additionally, research across multiple presentations will highlight novel technologies that enable early detection of disease recurrence to inform earlier interventions for patients who are more likely to benefit from treatment.

In total, data from more than 40 presentations will showcase progress with the next wave of anticancer medicines, novel insights in targeting resistance to therapy, and approaches that are advancing the personalised treatment of cancer.

Susan Galbraith, Senior Vice President and Head of Research and Early Development, Oncology R&D, said: "Our data at AACR (Free AACR Whitepaper) reflect a robust early-stage pipeline, poised to deliver life-changing medicines to patients living with cancer. Data for AZD5305 will demonstrate how the next wave of DNA damage response medicines can build on the success of PARP inhibitors, potentially allowing patients to stay on treatment longer. This innovative molecule is designed to optimise the therapeutic window of PARP inhibition, providing new opportunities for combination treatment with chemotherapy and targeted medicines."

The Company will share a Spotlight Theater Presentation: The Orchestrated Immune Response: Dynamic Forces Guiding Cancer Immunity, introducing a novel framework for understanding the role of the immune system in cancer, with the potential to reshape the way scientists develop medicines to counteract tumour growth.

AstraZeneca leaders will also participate in two educational symposia:

DNA Damage Response (DDR) Treatment: Evolving Diagnostic Approaches, Understanding of Replication Stress, and Resistance Mechanisms to DDR Targeting Therapies (Session #ADT04), with a discussion on targeting the replication stress response, which occurs when the genome is exposed to stresses that impede DNA replication.
Advances in Drug Delivery (Session #ADT08), with a discussion on the advances and innovations fueling the development of the next generation of antibody drug conjugates.
Key presentations will include:

Structural disclosure and key preclinical data for AZD5305, a next-generation PARP1 selective inhibitor
The introduction of AZD8853, a novel antibody targeting GDF15 for tumours refractory to immunotherapy treatment
Research from the HUDSON Phase II trial using deep learning algorithms on pathological images to identify features associated with progression on immunotherapy for patients with non-small cell lung cancer
A pooled analysis of interstitial lung disease data in patients treated with Enhertu across eight cancer trials
Two presentations from genome-wide CRISPR screenings that identify signalling in the Hippo pathway as an important driver of resistance in EGFR-mutated lung cancer and BRAF-mutated colon cancer
Data identifying a novel immunosuppressive myeloid gene signature for clinical biomarker development
Results from the ATRiUM Phase I trial, externally sponsored scientific research evaluating ceralasertib, an ATR inhibitor, and gemcitabine as combination therapy in biliary tract cancer
Key AstraZeneca presentations during AACR (Free AACR Whitepaper) 2021

Key AstraZeneca presentations during AACR (Free AACR Whitepaper) 2021
1Unless otherwise specified, all posters/presentations will be available starting 08:30 EDT on 10 April 2021.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On April 9, 2021 Sanofi acquired Tidal Therapeutics, a privately owned, pre-clinical stage biotech company with a novel mRNA-based approach for in vivo reprogramming of immune cells (Press release, Sanofi, APR 9, 2021, View Source [SID1234577780]). The new technology platform will expand Sanofi’s research capabilities in both immuno-oncology and inflammatory diseases, while likely having broad applicability to other disease areas as well. Sanofi acquired Tidal Therapeutics for an upfront payment of $160 million and up to $310 million upon achievement of certain milestones.

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!

"We anticipate that this next generation, off-the-shelf approach has the potential to bring CAR-T cell therapy to a much broader patient population," said Frank Nestle, Global Head of Research and Chief Scientific Officer at Sanofi. "We believe that the underlying mRNA targeting platform will create disruptive therapeutic approaches across a variety of oncology and autoimmune conditions."

Tidal Therapeutics utilizes a novel mRNA-based approach to in vivo reprogramming of immune cells. The technology is based on proprietary nanoparticles that deliver mRNA (messages) to reprogram immune cells inside the body. The technology delivers mRNA cargos selectively to designated types of cells in the body, with initial applications targeting specific types of immune cells. The in vivo approach is designed to provide similar efficacy to current ex vivo (outside the body) approaches where immune cells are genetically modified to enhance their therapeutic properties (such as chimeric antigen receptor [CAR]-expressing T-cells), with the potential for improved safety, outpatient dosing, and repeat dosing. Currently, Tidal Therapeutics has ongoing pre-clinical programs including in vivo re-programming of T cells or other types of immune cells for cancer indications.

"Teaming up with Sanofi gives us the opportunity to further develop our unique platform and rapidly apply it to ultimately help patients across a range of diseases," said Ulrik Nielsen, President and CEO, Tidal Therapeutics.

On April 9, 2021 Medical researchers from Case Western Reserve University, New York University (NYU), and University Hospitals reported that have been awarded a five-year, $3 million National Cancer Institute grant to develop and apply artificial intelligence (AI) tools for predicting which lung cancer patients will respond to immunotherapy (Press release, Case Western Reserve University, APR 9, 2021, View Source [SID1234577779]).

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!

A unique aspect of the Case Western Reserve-led study is that it will involve testing of their specific AI tools—for the first time during an ongoing clinical trial.

While these real-time treatment predictions will be used exclusively for research–and not for clinical diagnosis or treatment–the work is the next step toward trials that would allow physicians to apply the tools with participating patients.

"Clinical trials down the road will be our biggest test, but now we will be—for the first time—studying changes in the tissue-scan patterns of patients as they are being treated, and that will provide real-world context of our tools," said Anant Madabhushi, director of Case Western Reserve’s Center for Computational Imaging and Personalized Medicine . "Our AI tools have excelled in previous studies, but they have all been after-the-fact."

The researchers hope to predict which patients will have successful immunotherapy treatments based on previously unseen indicators in their initial computerized tomography (CT) scans. If successful, they will have more data to support using the AI diagnosis for lung cancer patients in clinical trials.

Madabhushi will again work with longtime collaborator Vamsidhar Velcheti, MD, director of thoracic oncology at NYU Langone’s Perlmutter Cancer Center, who previously worked in Cleveland.

Lung cancer remains the leading cause of cancer-related deaths worldwide, according to the World Health Organization. Dr. Velcheti said advances like the work by our team "to match patients to the right treatment—can improve outcomes and significantly reduce costs for patients with lung cancer" and that "tests to identify patients for appropriate immunotherapy treatments are a critical unmet need in the field of oncology.

"Using novel and sophisticated AI approaches, we are developing personalized strategies to identify patients who may benefit from combination-based immunotherapy approaches," Velcheti said. "This NIH grant will help advance our efforts to developing innovative approaches for patient selection and monitor patients on immunotherapy."

The team will also include the University Hospitals Radiology Department Amit Gupta, MD, and Robert Gilkeson, MD, both professors at the Case Western Reserve School of Medicine; Pingfu Fu, PhD, professor of Population and Quantitative Health Sciences at the School of Medicine.

AI and immunotherapy
The CCIPD digital imaging lab has become a global leader in using machine learning to discern patterns in digital images of tissue scans that can’t be seen by the human eye, including for various cancers.

The lab pioneered the use of AI to predict which patients would benefit from chemotherapy. And recent research by CCIPD scientists has demonstrated that AI and machine learning can help predict which lung cancer patients will benefit from immunotherapy.

Immunotherapy uses drugs to help the immune system fight the cancer, while chemotherapy uses drugs to directly kill cancer cells, according to the National Cancer Institute.

As with their chemotherapy work, the researchers can accurately predict who will or won’t benefit from immunotherapy by training a computer to find minuscule changes in patterns in CT scans taken when the lung cancer is first diagnosed. Those scans are then compared to scans taken after the first two to three cycles of immunotherapy.

Many cancer patients benefit from immunotherapy, but the treatment is expensive. Researchers hope to find a better way to identify which cancer patients would likely benefit. And those who wouldn’t avoid having to pay for what turns out to be ineffective and costly treatment.

Multiple partners, sites
The Case Western Reserve-led team will also work with the ECOG-ACRIN cancer research group, a membership-based organization that oversees scientific programs and research into cancer control and outcomes, therapeutic studies and biomarker sciences. Its members include the Case Comprehensive Cancer Center.

Stanton Gerson, director of the center and interim dean of the Case Western Reserve School of Medicine, called the new work a "pivotal study."

"When these data mature, we hope they will lead to improved clinical decision-making," Gerson said. "Such an advance could be transformative for physicians making those complex decisions on which treatment is best for a patient."

Madabhushi said the partnership with ECOG-ACRIN is significant because it marks the first time his center will work with a broader, cooperative oncology group. It would also further establish the "generalizability of our tools," he said, meaning the AI analysis developed at one site or with one set of patients should also be valid at a second testing site—something that has yet to be proven in AI-driven precision medicine.

Madabhushi said his team would also benefit from partnerships with pharmaceutical partners who provide researchers with access to completed retrospective clinical trial datasets of lung cancer patients previously treated with immunotherapy. This data will also help the researchers validate their tools.

The new work will also investigate how lung cancer tumors change in size and shape during immunotherapy. Oncologists now rely on whether tumors shrink or grow to determine whether treatment is working.

"But it turns out that is not a good way of assessing treatment response, and our AI research has shown that," Madabhushi said. "There are a certain percentage of patients whose tumors grow in size, but the immunotherapy is working, a phenomenon called ‘pseudoprogression.’ There are now other features that the computer can pull from the CT scan—both inside and in the vessels outside the tumor—that will give us a better indication."

He also said the AI would reveal the less frequent but troubling cases of "hyper-progression," in which a patient’s condition is actually worsened by immunotherapy.