On June 27, 2022 Daiichi Sankyo (TSE: 4568) and AstraZeneca reported it’s (LSE/STO/Nasdaq: AZN) trastuzumab deruxtecan has been recommended for approval in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens (Press release, AstraZeneca, JUN 27, 2022, View Source [SID1234616294]).

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!

Trastuzumab deruxtecan is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the DESTINY-Breast03 phase 3 trial, which were published in The New England Journal of Medicine. In the DESTINY-Breast03 trial, trastuzumab deruxtecan reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1) (hazard ratio [HR] = 0.28; 95% confidence interval [CI]: 0.22-0.37; p<0.0001) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The median progression-free survival (PFS) for patients treated with trastuzumab deruxtecan was not reached (95% CI: 18.5-NE) compared to 6.8 months for T-DM1 (95% CI: 5.6-8.2) as assessed by blinded independent central review (BICR).

The recommendation will now be reviewed by the European Commission, which has the authority to grant marketing authorizations for medicines in the EU.

In Europe, more than 530,000 cases of breast cancer are diagnosed annually.1 Approximately one in five cases of breast cancer are considered HER2 positive.2 Despite initial treatment with trastuzumab, pertuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.3,4 More treatment options are needed to further delay progression and extend survival.3,5,6

"Today’s CHMP opinion provides further validation of the significance of the DESTINY-Breast03 trial results, which for the first time showed superiority of trastuzumab deruxtecan in prolonging progression-free survival in patients previously treated for HER2 positive metastatic breast cancer as compared to another HER2 directed ADC," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "This positive CHMP opinion is an important step forward in bringing this potentially practice-changing medicine to patients in Europe to use earlier in the treatment of HER2 positive metastatic breast cancer and builds on the recent approval of trastuzumab deruxtecan in the U.S."

"This recommendation reflects the transformative progression-free survival benefit seen in the DESTINY-Breast03 trial compared to T-DM1, supporting trastuzumab deruxtecan as a potential new standard of care and setting a new benchmark in the treatment of HER2 positive metastatic breast cancer," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. "If approved by the European Commission, patients in Europe may be able to benefit from this important medicine earlier in the treatment of their disease, improving their chance for better outcomes."

Additional results from the DESTINY-Breast03 phase 3 trial showed that in the secondary endpoint analysis of PFS assessed by investigators, patients treated with trastuzumab deruxtecan experienced an improvement in PFS of 25.1 months (95% CI: 22.1-NE) compared to 7.2 months (95% CI: 6.8-8.3) for T-DM1 (HR=0.26; 95% CI: 0.20-0.35). There was a strong trend towards improved overall survival (OS) with trastuzumab deruxtecan (HR=0.56; 95% CI: 0.36-0.86; p=0.007172), however this analysis is not yet mature and is not statistically significant. Nearly all patients treated with trastuzumab deruxtecan were alive at one year (94.1%; 95% CI: 90.3-96.4) compared to 85.9% of patients treated with T-DM1 (95% CI: 80.9-89.7). Confirmed objective response rate (ORR) was more than doubled in the trastuzumab deruxtecan arm versus the T-DM1 arm (79.7% [n=208; 95% CI: 74.3-84.4] versus 34.2% [n=90; 95% CI: 28.5-40.3]).

The safety profile of the most common adverse events with trastuzumab deruxtecan in DESTINY-Breast03 was consistent with previous clinical trials with no new safety concerns identified. The most common grade 3 or higher drug-related treatment emergent adverse events in the trastuzumab deruxtecan arm were neutropenia (19.1%), thrombocytopenia (7.0%), leukopenia (6.6%), nausea (6.6%), anemia (5.8%), fatigue (5.1%), vomiting (1.6%), increased alanine aminotransferase (1.6%), decreased appetite (1.2%), increased aspartate aminotransferase (0.8%), diarrhea (0.4%) and alopecia (0.4%). Overall, 10.5% of patients had interstitial lung disease (ILD) or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD events (9.7%) were low grade (grade 1 (2.7%) or grade 2 (7.0%)) with two grade 3 (0.8%) events reported. No grade 4 or grade 5 ILD or pneumonitis events occurred.

About DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of trastuzumab deruxtecan (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Secondary endpoints include OS, ORR, duration of response, PFS based on investigator assessment and safety. DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. Results from DESTINY-Breast03 have been published in The New England Journal of Medicine. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Positive Breast Cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.7 More than two million cases of breast cancer were diagnosed in 2020, with nearly 685,000 deaths globally.7 In Europe, more than 530,000 cases of breast cancer are diagnosed annually.1 Approximately one in five cases of breast cancer are considered HER2 positive.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.8 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.9

Despite initial treatment with trastuzumab, pertuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.3,4 More treatment options are needed to further delay progression and extend survival.3,5,6

About Trastuzumab Deruxtecan
Trastuzumab deruxtecan is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, trastuzumab deruxtecan is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. Trastuzumab deruxtecan consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Trastuzumab deruxtecan (5.4 mg/kg) is approved in Canada, Israel and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy, based on results from the DESTINY-Breast03 trial. Trastuzumab deruxtecan is also approved in approximately 40 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

Trastuzumab deruxtecan (6.4 mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

About the Trastuzumab Deruxtecan Clinical Development Program
A comprehensive global development program is underway evaluating the efficacy and safety of trastuzumab deruxtecan monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for trastuzumab deruxtecan are currently under review in China, Europe, Japan and several other countries for the treatment of adult patients with HER2 positive unresectable or metastatic breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.

Trastuzumab deruxtecan is under review in Europe for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy, based on the results from the DESTINY-Breast04 trial. Patients with hormone receptor (HR) positive breast cancer must additionally have received or be ineligible for endocrine therapy.

Trastuzumab deruxtecan also is currently under review in the U.S. for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have a HER2 (ERBB2) mutation and who have received a prior systemic therapy based on the results from the DESTINY-Lung01 trial, and in Europe for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.

Trastuzumab deruxtecan recently was granted Breakthrough Therapy Designation in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results of the DESTINY-Breast04 trial. Patients with hormone receptor (HR) positive breast cancer should additionally have received or be ineligible for endocrine therapy.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of trastuzumab deruxtecan and datopotamab deruxtecan.

On June 27, 2022 Transgene (Euronext Paris: TNG) (Paris:TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, and BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported that positive progress and safety data of the ongoing Phase I/IIa trial evaluating BT-001 in patients with solid tumors, including melanoma (Press release, Transgene, JUN 27, 2022, View Source [SID1234616293]).

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 initial data generated in Phase I part A demonstrated that BT-001 alone is well tolerated, with first signs of anti-tumor activity in a hard-to-treat population and confirmed the mechanism of action of BT‑001 as a single agent. The initial findings are as follows:

After administration, the virus was found in the tumors after several days. This suggests that BT‑001 is able to persist and replicates within tumors;
This finding is consistent with the expression of the anti-CTLA-4 observed in the tumor with no detectable systemic exposure;
No spreading in blood or biological fluids has been detected, suggesting high tumor specificity;
Tumor shrinkage was observed in one patient in the first cohort.
The part A of the Phase I trial aims to establish the tolerability of BT-001 and to determine the dose and administration schedule for further development. Repeated (every 3 weeks) and ascending doses of intratumoral administration of BT‑001, as a single agent, will be administered to up to 18 patients with metastatic/advanced tumors.

The first two dose levels have been successfully completed, with 12 patients dosed to date. The Safety Review Committee (SRC) has stated that the safety profile supports escalation to the highest dose level of Phase I part A.

The Phase I part B is planned to start in H2 2022. This part will assess the combination of intratumoral injections of BT-001 with intravenous administrations of the anti-PD1 antibody pembrolizumab.

BT-001 is based on Transgene’s patented oncolytic vector and is encoding BioInvent’s proprietary anti‑CTLA‑4 antibody; it is codeveloped by the two biotechnology companies.

About the trial

The ongoing Phase I/IIa (NCT04725331) study is a multicenter, open label, dose-escalation trial evaluating BT-001 as a single agent and in combination with pembrolizumab (anti-PD-1 treatment). Patient inclusions are ongoing in Europe (France, Belgium) and the trial has been authorized in the US.

This Phase I is divided into two parts. In part A, patients with metastatic/advanced tumors receive single agent, intra-tumoral administrations of BT-001. Part B will explore the combination of intra-tumoral injections of BT-001 with pembrolizumab. The Phase IIa will evaluate the combination regimen in several patient cohorts with different tumor types. These expansion cohorts will offer the possibility of exploring the activity of this approach to treat other malignancies not traditionally addressed with this type of treatment.

About BT-001

BT-001 is an oncolytic virus generated using Transgene’s Invir.IO platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and the human GM-CSF cytokine. By selectively targeting the tumor microenvironment, BT-001 is expected to elicit a much stronger and more effective antitumoral response. As a consequence, by reducing systemic exposure, the safety and tolerability profile of the anti-CTLA-4 antibody may be greatly improved.

BT-001 is being co-developed as part of a 50/50 collaboration on oncolytic viruses between Transgene and BioInvent. To know more on BT-001, watch our video here.

On June 27, 2022 Alaunos Therapeutics, Inc. ("Alaunos" or the "Company") (Nasdaq: TCRT), a clinical-stage oncology-focused cell therapy company, reported that the Company has extended its Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), an institute of the National Institutes of Health, using the Alaunos Sleeping Beauty technology through January 2025 (Press release, Alaunos Therapeutics, JUN 27, 2022, View Source [SID1234616291]).

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!

Under the terms of the CRADA, the NCI will work to generate proof of concept utilizing the Company’s proprietary non-viral Sleeping Beauty technology for personalized TCR-T cell therapy. In this setting, T-cell receptors (TCRs) that react to the patient’s tumor will be identified from the patient and used to generate a TCR-T cell therapy. This approach could potentially apply to a wide range of solid tumor cancer patients. Alaunos believes that the non-viral Sleeping Beauty technology could rapidly and cost effectively produce safe and potent TCR-T cell therapies without the complexity of gene editing or viral approaches. Research conducted under the CRADA will be led by Steven A. Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at the NCI’s Center for Cancer Research.

"We are privileged to extend the productive collaboration with Dr. Rosenberg, a cell therapy pioneer. Dr. Rosenberg and the NCI are working to develop personalized cancer therapies using our novel TCR-T cell platform," commented Kevin S. Boyle, Sr., Chief Executive Officer of Alaunos. "Our collaboration reinforces our commitment to improving the lives of cancer patients with solid tumors. We look forward to continuing our collaborating with Dr. Rosenberg and his team to generate proof of concept in this personalized TCR-T approach."

Drew Deniger, Ph.D., Vice President, Research & Development at Alaunos added, "Having worked alongside Dr. Rosenberg for many years, I am confident that his team at the NCI will be successful in developing personalized TCR-T therapies using our non-viral Sleeping Beauty technology. As the world’s experts in Sleeping Beauty, we believe that our non-viral means of adding the TCR to T cells is well suited for a personalized approach, with potential to further increase the addressable population for TCR-T therapies."

On June 27, 2022 INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help protect people from infectious diseases and treat people with cancer and HPV-associated diseases, reported the appointment of Dr. Michael Sumner, MB BS, MBA, as Chief Medical Officer (CMO) (Press release, Inovio, JUN 27, 2022, View Source [SID1234616290]). Dr. Sumner will oversee INOVIO’s clinical-stage pipeline of DNA medicines, global clinical development, clinical operations and biostatistics efforts, as well as regulatory affairs, pharmacovigilance and medical affairs. He will serve on the company’s executive leadership team and will report to INOVIO’s President and Chief Executive Officer, Dr. Jacqueline Shea.

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!

INOVIO’s President and Chief Executive Officer, Jacqueline Shea, Ph.D., said, "INOVIO is pleased to welcome Dr. Sumner to INOVIO. An industry veteran and a member of the Royal College of Physicians, Dr. Sumner’s clinical development and medical affairs expertise and track record of helping guide companies through regulatory approval and commercialization make him an important addition to the INOVIO team."

Dr. Sumner joins INOVIO after serving as CMO of Orexo AB since 2013. He previously held numerous European- and US-based leadership roles at Novartis Pharmaceuticals, Aventis Behring, Novo Nordisk and Shire Pharmaceuticals. Dr. Sumner brings over 25 years of extensive pharmaceutical, medical and clinical experience driving numerous late-stage product approvals and supporting successful commercial products on a global basis across multiple therapeutic areas.

Dr. Sumner received his medical degree from the University of London, is a member of the Royal College of Physicians, and holds a Master of Business Administration from Henley Management College, UK.

"I am pleased to join INOVIO as CMO and look forward to working with the team to unlock the power of the DNA Medicines platform to address unmet medical need," said Dr. Sumner.

On June 27, 2022 Hoffmann-La Roche reported to invite you to an analyst event on Tuesday, 26 July 2022, to discuss Roche’s Diagnostics Division, in conjunction with the American Association for Clinical Chemistry (AACC) Annual Meeting and Clinical Lab Exposition in Chicago, Illinois (July 24-28, 2022) (Press release, Hoffmann-La Roche, JUN 27, 2022, View Source [SID1234616289]).

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!

AACC brings together the global leaders in clinical chemistry, molecular diagnostics and lab management, and is the largest dedicated exhibition of equipment, instruments and services for clinical laboratories in the world.

The Analyst Event will start with a presentation on the Diagnostics Division and on AACC highlights followed by a Q&A session.