On March 3, 2025 Daiichi Sankyo reported positive topline results from the DESTINY-Gastric04 phase 3 trial showed ENHERTU (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of overall survival (OS) compared to ramucirumab and paclitaxel in patients with second-line HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (Press release, Daiichi Sankyo, MAR 3, 2025, View Source [SID1234650858]).

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At a planned interim analysis, the Independent Data Monitoring Committee recommended unblinding the trial based on the superior efficacy of ENHERTU.

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).

Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%.1,2 Following disease progression in the first-line metastatic setting of HER2 positive gastric cancer, there historically have been no HER2 directed medicines that have demonstrated a survival benefit in the second-line metastatic setting in a randomized clinical trial.3

ENHERTU is currently approved in more than 65 countries based on DESTINY-Gastric01, a randomized phase 2 trial, and DESTINY-Gastric02 and DESTINY-Gastric06, two single-arm phase 2 trials. DESTINY-Gastric04 is the first phase 3 trial of ENHERTU in HER2 positive advanced gastric cancer.

"ENHERTU is the first HER2 directed medicine to demonstrate an improvement in overall survival in a randomized phase 3 trial in the second-line metastatic setting of patients with HER2 positive gastric cancer, reinforcing previous findings seen in our other earlier phase gastric cancer trials," said Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo. "With these DESTINY-Gastric04 results, we will work with global regulatory authorities to seek approval in regions where ENHERTU is not currently indicated as a second-line option, as well as work to secure full approval in regions where ENHERTU is conditionally approved."

"We are committed to advancing the care of patients with metastatic gastric cancer and continuing to understand the role of ENHERTU in earlier lines of treatment," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. "The results of DESTINY-Gastric04 show that second-line treatment with ENHERTU can extend survival compared with a chemotherapy-based regimen and should be considered for all eligible patients with HER2 positive metastatic gastric cancer."

The safety profile seen in DESTINY-Gastric04 is consistent with the established safety profile of ENHERTU.

Data from DESTINY-Gastric04 will be presented at an upcoming medical meeting and shared with global regulatory authorities.

About DESTINY-Gastric04
DESTINY-Gastric04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (6.4 mg/kg) versus ramucirumab and paclitaxel in patients with HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen.

The primary endpoint is OS. Secondary endpoints include investigator-assessed progression-free survival, objective response rate, duration of response, disease control rate and safety.

DESTINY-Gastric04 enrolled 494 patients in Asia, Europe and South America. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Positive Gastric Cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth leading cause of cancer-related death.1,2 Approximately one million cases of gastric cancer were diagnosed in 2022.2 Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%.1,2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including gastric cancer.4 Approximately one in five gastric cancers are considered HER2 positive.4,5

Following disease progression in the first-line metastatic setting of HER2 positive gastric cancer, there historically have been no HER2 directed medicines that have demonstrated a survival benefit in the second-line metastatic setting in a randomized clinical trial.3

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 75 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 75 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 the U.S. for the treatment of adult patients with unresectable or metastatic HR positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA approved test, that have 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 50 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 65 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 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 monotherapy across multiple HER2 targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

On March 3, 2025 Immunovia (IMMNOV: Nasdaq Stockholm), the pancreatic cancer diagnostics company, reported that the results of its CLARITI study have been selected for a distinguished plenary presentation at the upcoming Digestive Disease Week (DDW) 2025 conference, taking place May 5, 2025 (Press release, Immunovia, MAR 3, 2025, View Source [SID1234650857]).

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The CLARITI study was selected as one of only six abstracts to be presented at the AGA Institute Council’s Pancreatic Disorders Section Distinguished Abstract Plenary—an honor reserved for research demonstrating exceptional scientific and clinical impact.

Dr. Aimee Lee Lucas, Chief of Gastroenterology and Hepatology at Mount Sinai West and Mount Sinai Morningside Hospitals and Professor of Medicine at Icahn School of Medicine, will present the CLARITI study findings at DDW 2025. Her presentation, titled "Clinical validation of a novel blood-based multi-biomarker test for the early detection of pancreatic ductal adenocarcinoma (PDAC) in an independent high-risk population shows similar high performance as observed in its model development study," highlights the study’s robust methodology and the strong performance of Immunovia’s next-generation test.

As a member of the Immunovia Scientific Advisory Board, Dr. Lucas was integral to the study’s design and played a key role in the collection of blood samples.

"I am excited to present these data at the world’s largest conference for gastroenterologists. Selection of these study results for a distinguished plenary oral presentation underscores the rigor of the CLARITI validation study and the strong performance of the Immunovia test in the study," says Dr. Aimee Lee Lucas.

"We are very proud to see the CLARITI study receive this remarkable recognition. It’s a strong statement about the quality of our science and it highlights the importance of the unmet clinical need our new test addresses," says Jeff Borcherding, Immunovia CEO.

On March 3, 2025 Compugen Ltd. (NASDAQ: CGEN) (TASE: CGEN) a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported that management will participate in a fireside chat at the Leerink Partners Global Healthcare Conference, Miami Beach, Florida, on Tuesday, March 11, 2025 at 8:00 AM ET (Press release, Compugen, MAR 3, 2025, View Source [SID1234650856]).

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A live webcast of the presentation will be available on the events page of the Investor Relations section of Compugen’s website at www.cgen.com. A replay will be available following the live event.

On March 3, 2025 CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, reported that the first patient has been successfully dosed in the global multicenter Phase I clinical trial of its novel PD-1/VEGF/CTLA-4 trispecific antibody, CS2009, with no infusion reactions or other adverse events observed (Press release, CStone Pharmaceauticals, MAR 3, 2025, View Source [SID1234650855]).

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This trial aims to evaluate the clinical potential of CS2009 in a wide range of advanced solid tumors including, but not limited to, non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer, in efforts to advance the development of innovative tumor immunotherapies.

CS2009, an innovative trispecific antibody designed and developed by CStone, combines three clinically validated targets—PD-1, VEGFA, and CTLA-4—and exerts multidimensional anti-tumor effects through synergistic actions. Specifically, anti-PD-1 activity that reverses T cell exhaustion, anti-CTLA-4 activity that promotes T cell activation and proliferation, while anti-VEGFA activity blocks tumor angiogenesis and improves the tumor micro-environment (TME). In the TME, anti-PD-1 and anti-CTLA-4 activities are significantly enhanced by crosslinking with VEGFA. Meanwhile, CS2009 preferentially blocks PD-1 and CTLA-4 on double-positive tumor-infiltrating T cells while minimizing interference with CTLA-4 regulation in peripheral T cells, thus potentially offering enhanced efficacy with lower systemic toxicity.

In preclinical studies, CS2009 demonstrated superior anti-tumor activity compared to potential competitors. By combining CTLA-4 inhibition with PD-1 and VEGFA blockade, CS2009 may further enhance benefits for patients with low or negative PD-L1 expression, who respond poorly to PD-(L)1 therapies. This well positions CS2009 as a next-generation, first- or best-in-class immunotherapy backbone, with the potential to replace current anti-PD-(L)1-based therapies.

Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, stated, "The initiation of the first-in-human study for CS2009 marks a breakthrough in our clinical development. Our robust preclinical data have confirmed CS2009’s potential across a wide range of solid tumor indications. In in vitro studies, CS2009 demonstrated its ability to effectively and specifically activate tumor-infiltrating T cells, as well as robust synergistic effect with anti-VEGF activity; in immunocompetent mouse models, CS2009 showed stronger anti-tumor effects than both PD-1/CTLA-4 and PD-1/VEGF bispecific antibodies; and in toxicology studies, CS2009 exhibited a safety margin which was greater than the PD-1/CTLA-4 bispecific antibody and comparable to the PD-1/VEGF bispecific antibody. These results give us confidence in CS2009’s clinical potential. We look forward to sharing additional clinical data that will further validate its safety and anti-tumor activity, paving the way for a new era in cancer immunotherapy."

Dr. Qingmei Shi, Chief Medical Officer of CStone, added, "We are pleased to achieve the first-patient-dosed milestone for CS2009, an innovative trispecific antibody that can potentially offer balanced efficacy and safety while addressing the unmet medical needs in patients with low or negative PD-L1 expression. We expect to see rapid and encouraging progress in this study and are committed to bringing improved treatment options to patients with solid tumors worldwide. We appreciate the exceptional efforts of our clinical team, who managed through the entire process—from submitting the clinical trial application in Australia to dosing the first patient—in two months that overlapped with major holidays in China and Australia. This is another testament to CStone’s outstanding clinical development efficiency and unwavering commitment to serving patients."

Currently, the multicenter Phase I clinical trial of CS2009 is being conducted in Australia, with plans to expand into China and the United States in the near future.

About CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody)

CS2009 is a trispecific antibody targeting PD-1, VEGFA, and CTLA-4, with the potential to be first- or best-in-class for major tumor types. Its differentiated molecular design combines three clinically validated targets, preferentially invigorating exhausted tumor infiltrating lymphocytes (TILs) while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. CS2009 covers a wide range of cancers, including but not limited to non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer.

In November 2024, CStone presented preclinical data for CS2009 at the 39th SITC (Free SITC Whitepaper) Annual Meeting. These results show that CS2009 exhibits superior anti-tumor activity compared to potential competitors, including PD-1/CTLA-4 bispecific antibodies, PD-1/VEGF bispecific antibodies, and PD-1/CTLA-4 combination therapies.

On March 3, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported a research collaboration with ATTMOS as part of its efforts to build a physics-based computational small molecule discovery platform that rapidly unlocks what are currently perceived as undruggable oncology targets (Press release, Ideaya Biosciences, MAR 3, 2025, View Source [SID1234650854]).

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The collaboration will integrate IDEAYA’s differentiated and proven capabilities in structural biology and pharmaceutical drug discovery across multiple first-in-class oncology targets with ATTMOS’s capabilities in computational chemistry method development, high performance computing, and software development. The focus of the partnership will be to engineer and optimize a workflow solution for high-throughput absolute binding free energy perturbation predictions (ABFEP) of first-in-class drug candidate molecules. This approach enables application of gold-standard physics-based statistical mechanics calculations of protein-ligand affinities at the scale required for virtual screens and represents what could become the industry’s go-to standard for high-speed and high probability-of-success drug hit-finding against structurally-enabled novel biological targets.

"Current AI/ML-enabled drug discovery approaches have been largely applied to either already drugged targets or well-understood biological target classes and often fail when applied to first-in-class target opportunities. IDEAYA continues to enhance its computational drug discovery capabilities to pursue first-in-class oncology targets that are perceived as undruggable," said Michael White, Ph.D., Chief Scientific Officer, IDEAYA Biosciences. "Our partnership with ATTMOS will enable us to apply the principles of engineering to the field of drug discovery, at scale, for efficient prosecution of unprecedented oncology targets," said Paul Barsanti, Ph.D., Chief Technology Officer, IDEAYA Biosciences.

The collaboration will leverage the Amber molecular dynamics suite as the GPU-accelerated back-end free energy simulation engine. IDEAYA will train and evaluate ABFEP-based active learning cycles based on extensive ground-truth data sets derived from its successful wet-lab drug discovery campaigns against novel targets. These models will be used to screen enormous libraries of synthetically tractable chemical space for accurate and efficient de novo discovery of small molecule ligands for new targets. The work aims to overcome the limitations of current virtual screening approaches and accelerate the discovery of novel small molecule oncology therapeutics that address unmet clinical need.