On June 9, 2025 Daiichi Sankyo reported that the first patient has been dosed in the DESTINY- Endometrial01 phase 3 trial evaluating ENHERTU (trastuzumab deruxtecan) in combination with rilvegostomig or pembrolizumab versus platinum-based chemotherapy (carboplatin and paclitaxel) in combination with pembrolizumab as a first-line therapy in patients with HER2 expressing (IHC 3+/ 2+), mismatch repair proficient (pMMR) primary advanced or recurrent endometrial cancer (Press release, Daiichi Sankyo, JUN 9, 2025, View Source [SID1234653780]). DESTINY- Endometrial01 will be conducted in collaboration with The GOG Foundation, Inc. (GOG-F) and the European Network of Gynecological Oncological Trial (ENGOT).

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ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Endometrial cancer that is recurrent or diagnosed in advanced stages has a median overall survival of up to 30 months.1 While there have been recent treatment advances, there is still a need to further improve outcomes for patients. HER2 expression (IHC 3+/2+) is associated with aggressive disease and is present in 18% to 56% of endometrial cancers.2,3,4,5,6 There currently are no HER2 directed medicines approved in the first-line endometrial cancer setting.

"Following the positive results in the endometrial cancer cohort of DESTINY-PanTumor02, which contributed to a tumor agnostic approval for previously treated patients with HER2 positive metastatic tumors in several regions, we are initiating this first phase 3 trial of ENHERTU in the first-line setting of advanced endometrial cancer," said Mark Rutstein, MD, Head, Therapeutic Area Oncology Development, Daiichi Sankyo. "The DESTINY-Endometrial01 trial will help us better understand the role of ENHERTU in combination with immunotherapy as a potential treatment strategy to help improve outcomes compared to the current standard of care in this specific gynecological cancer setting."

About DESTINY-Endometrial01
DESTINY-Endometrial01 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) in combination with rilvegostomig or pembrolizumab versus platinum-based chemotherapy (carboplatin and paclitaxel) in combination with pembrolizumab as a first-line therapy in patients with HER2 expressing (IHC 3+/2+), pMMR, primary advanced (stage III/IV) or first recurrent endometrial cancer of any histologic subtype except sarcoma. Patients will be randomized in a 1:1:1 ratio to receive either ENHERTU in combination with rilvegostomig, ENHERTU in combination with pembrolizumab or platinum-based chemotherapy in combination with pembrolizumab.

The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review (BICR). The key secondary endpoint is overall survival. Additional secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response and safety.

DESTINY-Endometrial01 will enroll approximately 600 patients across multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody. The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN). Pembrolizumab (KEYTRUDA) is Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy.

About Endometrial Cancer
Endometrial cancer is the second most common gynecologic cancer and the sixth most common cancer among women worldwide.7 Approximately 420,000 endometrial cancer cases were diagnosed in 2022, with more than 97,000 deaths globally.8 Incidence and mortality rates of endometrial cancer are expected to increase by approximately 61% and 87% respectively by 2050.9 Patients with advanced or recurrent endometrial cancer have a poor prognosis, with a median overall survival of up to 30 months.1

Endometrial cancer comprises several molecular subtypes.10 Approximately 20% to 30% of all endometrial cancers exhibit high microsatellite instability (MSI) due to a defective mismatch repair system and are classified as MSI-high or MMR deficient (dMMR).10 The remaining 70% to 80% of cases are considered mismatch repair proficient (pMMR) tumors.10

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors.11 HER2 expression (IHC 3+/ 2+) is present in 18% to 56% of endometrial cancers and is associated with markers of aggressive disease.2,3,4,5,6 HER2 expression is observed almost exclusively in pMMR tumors.2

Standard of care first-line treatment of advanced or recurrent endometrial cancer has long included carboplatin plus paclitaxel.12 The treatment paradigm has recently evolved to incorporate an immune checkpoint inhibitor with carboplatin and paclitaxel, particularly for patients with dMMR endometrial cancer; however, the benefit of this treatment regimen in pMMR endometrial cancer is less pronounced.13,14,15,16 There currently are no HER2 directed medicines approved in the first-line endometrial cancer setting.

About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4 mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) 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 the results from the DESTINY-Breast03 trial.

ENHERTU (5.4 mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) 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.

ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that has progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

ENHERTU (5.4 mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 70 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (5.4 mg/kg) is approved in Brazil, Israel, Russia, Saudi Arabia, Switzerland, Taiwan, U.K. and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the ENHERTU Clinical Development Program
A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2 targetable cancers.

On June 9, 2025 TuHURA Biosciences, Inc. (NASDAQ:HURA) ("TuHURA" or the "Company"), a Phase 3 immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, reported that the FDA has removed the manufacturing-related partial clinical hold on the Company’s Phase 3 accelerated approval trial for IFx-2.0, thereby allowing the trial to proceed as agreed to under the previously announced SPA Agreement with the FDA (Press release, TuHURA Biosciences, JUN 9, 2025, View Source [SID1234653778]).

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"We are grateful for the collaborative interaction with the reviewers at the Office of Therapeutic Products (OTP) and the Oncology Center of Excellence (OCE), including their quick response time and, importantly, their helpful recommendations going forward," stated James Bianco, M.D., President and Chief Executive Officer of TuHURA Biosciences.

"The removal of the partial clinical hold allows TuHURA to begin the trial’s initiation and activation of clinical sites for the Phase 3 accelerated approval trial of IFx-2.0," continued Dr. Bianco. "We are also pleased that the removal of the partial clinical hold represents the achievement of the second milestone funding condition under our recently announced private placement, thereunder trigging the payment to the Company of an additional $2.23 million under the financing."

The Company’s Phase 3 accelerated approval trial of IFx-2.0, will be conducted under an SPA Agreement with the U.S. FDA, and will evaluate IFx-2.0 as an adjunctive therapy administered weekly for three weeks concurrent with the approved dose and schedule for Keytruda compared to Keytruda plus placebo in the first line treatment of patients with advanced or metastatic MCC. Keytruda is currently approved in MCC under accelerated approval based on Overall Response Rate (ORR). The pivotal trial for IFx-2.0 is expected to enroll 118 across approximately 22 to 25 U.S. sites. Trial participants will be randomized on a 1:1 basis and receive Keytruda in both arms, for up to two years, or until disease progression or Keytruda related toxicities. The primary endpoint for the trial is ORR with a key secondary endpoint of Progression Free Survival (PFS). Other secondary endpoints are safety, duration of response, and overall survival. Accelerated approval is based on the successful achievement of the ORR primary endpoint. PFS, the key secondary endpoint, if successfully achieved, without a detrimental effect on overall survival, could satisfy the requirement for regular approval without the requirement for a post approval confirmatory trial (in contrast to most accelerated approval trials).

On June 9, 2025 ModeX Therapeutics Inc., an OPKO Health company (NASDAQ: OPK), reported the creation of a Scientific Advisory Board to provide counsel and insight into the development of ModeX’s immunology and oncology-focused pipeline featuring potential first-in-class multispecific antibodies and vaccines developed with its proprietary MSTAR platform technology (Press release, Opko Health, JUN 9, 2025, View Source [SID1234653777]). Aligned with the company’s primary areas of focus, the board is comprised of established leaders across complex diseases involving the immune system including cancer, immune-mediated disease, and infectious diseases.

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The founding members include Drs. John Heymach, Ronald Levy, Myron Cohen, and Rafi Ahmed. Each of these globally recognized researchers brings notable contributions to biomedical research and the translation of therapeutics to impact public health.

"We are excited to welcome to our team four eminent scientists who share our vision of advancing next-generation immune therapies that simultaneously attack multiple targets and help patients overcome devastating diseases," said Gary Nabel, M.D., Ph.D., President and Chief Executive Officer of ModeX, and Chief Innovation Officer of OPKO.

Members of the ModeX Scientific Advisory Board include the following:

Rafi Ahmed, Ph.D. – Director of the Emory Vaccine Center and Georgia Research Alliance Eminent Scholar, Emory University School of Medicine. Dr. Ahmed’s work in immunology has been highly influential in shaping our understanding of immunological memory to vaccines and T cell exhaustion during chronic viral infection. These findings have led to improved vaccination strategies and to the development of PD-1 directed immunotherapy for cancer. Dr. Ahmed is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences.
Myron Cohen, M.D. – Professor of Medicine, Microbiology, and Immunology at the University of North Carolina (UNC), Director at the UNC Institute for Global Health and Infectious Diseases, Associate Vice Chancellor for Global Health at UNC, and Associate Director of the UNC Center for AIDS Research. Dr. Cohen’s career has focused on the transmission of STDs, including HIV, and strategies for prevention. He was an architect of landmark studies that demonstrated that treatment of HIV prevents its transmission, a catalyst for current global HIV prevention efforts.
John Heymach, M.D., Ph.D. – Chair of Thoracic/Head and Neck Medical Oncology and a professor at the University of Texas MD Anderson Cancer Center. He is a co-leader of the Center’s Lung Cancer Moon Shot and serves as a Principal Investigator of lung cancer programs funded by the National Cancer Institute, LUNGevity, and the American Association for Cancer Research (AACR) (Free AACR Whitepaper). His research has led to novel therapeutic approaches for multiple types of lung cancer, and as a clinical investigator, he leads several biomarker-directed clinical trials using targeted and immunotherapy agents.
Ronald Levy, M.D. – Professor of Medicine and Co-Director of the Hematologic Malignancies Program at Stanford University. He also serves as Associate Director of Translational Science for the Stanford Cancer Institute. His research has focused on monoclonal antibodies and the study of malignant lymphoma. Dr. Levy was a pioneer in successfully treating cancer with monoclonal antibodies and played a role in the development of rituximab for the treatment of lymphomas.
"Through my research I have witnessed how targeted antibody therapies have transformed the treatment of cancer and profoundly impacted patients’ lives globally," said Dr. Ronald Levy, a Professor of Medicine, and Co-Director of the Hematologic Malignancies Program at Stanford University. "Multispecific treatments are writing the next chapter by overcoming the limitations of existing antibody treatments and expanding accessibility to many more patients. Alongside the experts joining me on this advisory board, I look forward to helping the ModeX team fulfill this mission."

"Drs. Heymach, Levy, Cohen, and Ahmed are globally recognized leaders in their respective field. We are grateful for their interest, counsel and support to achieve the full potential of our proprietary multispecific antibody technologies including to revolutionize the treatment landscape for millions of patients," said Phillip Frost, M.D., Chairman and Chief Executive Officer, and Elias Zerhouni, M.D., Vice Chairman and President, of OPKO.

Beyond bispecifics: ModeX’s multispecific antibody platform
Multispecific therapeutics represent the future of medicine. Many untreatable or complex conditions arise from multiple disease pathways, yet most medicines only act on a single target. ​​ ModeX overcomes these challenges by combining natural protein structures to create unique multispecific medicines that can harness the immune system and address the complexity of disease.

On June 9, 2025 Neurogene presented its corporate presentation (Presentation, Neurogene, JUN 9, 2025, View Source [SID1234653776]).

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On June 9, 2025 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies for cancer and autoimmune diseases, reported that Patient 009 in the Phase 1 trial of INB-200 for newly-diagnosed GBM has recently reached a significant clinical milestone (Press release, In8bio, JUN 9, 2025, View Source [SID1234653774]). The patient, with a grade 4, IDH-mutant glioma, has been in remission and surviving for 4 years having been treated with INB-200. The patient is doing well, has returned to work and has a good quality of life post-treatment with INB-200. Patient 009’s clinical progress and 4-year remission far surpasses progression-free outcomes observed in other clinical trials of IDH-mutant glioma patients.

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"Surviving four years without progression in newly diagnosed astrocytoma WHO4 IDH mutated is a significant achievement demonstrating the potential activity of gamma-delta T cells," said Dr. Burt Nabors, Principal Investigator of the INB-200 trial and Vice-Chair of Research of Neurology and Director for the UAB Division of Neuro-oncology. "This outcome further highlights the potential impact of INB-200 in one of the most aggressive, difficult-to-treat and deadly cancers."

IN8bio recently presented updated Phase 1 data from the INB-200 trial at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The results showed that repeated doses of INB-200 demonstrated an extended mPFS of 16.1 months, more than double the expected 6.9 months typically observed with the standard-of-care Stupp protocol in newly diagnosed GBM. INB-200 is the first genetically modified gamma-delta T cell therapy evaluated in GBM and has demonstrated a favorable safety profile and signals of long-term benefit.

"We are thrilled that our study participant has reached this incredible milestone," said William Ho, CEO and co-founder, IN8bio. "This type of long-term survival and life changing clinical impact is exactly what we strive to achieve at IN8bio. The current standard-of-care for newly diagnosed GBM has not advanced beyond an overall survival of 14-16 months in over two decades. This is a powerful testament to what’s possible when we harness the unique biology of gamma-delta T cells."