Tremelimumab

None Written by: Philippe Menu, MD, Ph.D, MBA – EVP, Chief Medical Officer and Chief Product Officer, SOPHiA GENETICSThe Multimodal Imperative: How AI-Driven Technology is Driving Impactful ChangesIn today’s fast-moving biopharma landscape, companies face increasing pressure to deliver the right treatment, to the right patient, at the right time, faster and more efficiently. As our understanding of disease biology complexity grows, legacy R&D models are increasingly strained to deliver timely and impactful innovations.Just two decades ago, cancer was largely considered an organ-based disease. For example, lung cancer, despite known histological subtypes, was uniformly treated as a single disease — chemotherapy for all. Today, thanks to advances in clinical genomics, we recognize lung cancer as a collection of rare diseases, defined by a long tail of distinct genomic alterations. Targeted therapies have emerged to improve patient outcomes for eligible patients; however, high unmet medical needs remain. Most patients with metastatic lung cancer do not have a molecularly defined cause and are treated with immunotherapy as standard of care. Despite massive investments, single-biomarker approaches have repeatedly failed to reliably predict which patients will respond to immunotherapy.To address these challenges, precision medicine must evolve from a siloed, single-biomarker approach to a more integrated, multimodal approach combining genomic, imaging, clinical, and biological data. Intuitively, taking a more holistic view of the patient, tumor, and host environment should open a stronger window into the biology of health and disease. However, to fully realize this potential, we must transform the data infrastructure that underpins precision medicine. This includes breaking down silos across data types, harmonizing and standardizing inputs, and fostering real-world knowledge sharing across institutions.The Challenge of Unveiling Novel InsightsOver the past decade, we have seen a dual revolution in healthcare: the explosion of multiple types of digital health data being produced at scale in clinical routine (e.g., genomics, imaging, EHR entries) and generational breakthroughs in analytics capabilities (e.g., machine learning, foundational models). In theory, this combination should have unlocked the full potential of precision medicine, but in practice, we are arguably still at its Stone Age. One of the root causes is data fragmentation: healthcare data is still siloed, unharmonized, and difficult to integrate. The tools needed to bring these diverse data types together are often inadequate, and the ecosystem lacks strong incentives for large-scale data and insights sharing across institutions, while preserving privacy.On the biopharma side, we see increasing interest and expertise for AI-driven approaches on specific data modalities (e.g., digital pathology), however, these initiatives are still rarely connected within a truly multimodal framework. Proprietary clinical trial databases, meanwhile, remain difficult to harmonize and merge together due to heterogeneous patient consent, compliance issues, and required investments.What Happens When You Connect the Proverbial (Multimodal) Dots?Multimodal AI-driven technology is already driving significant advances in our understanding of health and disease. By seamlessly integrating and analyzing diverse data sources, it enables a more holistic perspective of complex diseases like cancer, and the patient beyond the disease.The practical application of AI-powered multimodal technology can help biopharma companies address drug development challenges and overall optimize this process (Figure 1).Figure 1. Driving Efficiency Across the Drug Development Continuum with Multimodal AI-driven Technologies.At SOPHiA GENETICS we believe that multimodal AI is no longer an option but a necessity to accelerate precision medicine. Our cloud-based SOPHiA DDM™ Platform seamlessly integrates and standardizes diverse data types into a unified analytical framework, comprising state-of-the-art specialized computational modules for data processing and analysis (e.g., genomics, radiomics), and a dedicated multimodal factory. This engine combines, extracts, and structures complex multimodal data to fuel the development of predictive analytics, delivering actionable insights that empower data-driven decision-making (Figure 2).Figure 2. The SOPHiA DDM™ Platform enables the analysis of multimodal data at scale.The potential of multimodal approaches is evident in the initiatives we are leading here at SOPHiA GENETICS, notably the TRIDENT project (Skoulidis et al, 2024). In this retrospective multimodal re-analysis of AstraZeneca’s Phase 3 POSEIDON trial (NCT03164616), AI-powered models were trained on integrated clinical trial data to predict treatment benefit. The goal was to identify patient subpopulations that may derive greater benefit from the addition of a CTLA-4 inhibitor to a PD-L1 and chemotherapy backbone in treatment-naïve metastatic lung cancer. These models yielded signatures identifying approximately 50% of the trial population in scope that would be predicted to benefit from the addition of CTLA-4 inhibition, with a hazard ratio reduction from 0.88 (95% CI, 0.68-1.12) to 0.56 (95% CI, 0.33-0.97) in the non-squamous histology population (Figure 3). These multimodal signatures are clinically interpretable and can be readily deployed in the real-world setting on the SOPHiA DDM™ Platform for further clinical research.Figure 3. Multimodal re-analysis of the non-squamous patient population in the Phase 3 POSEIDON trial.The Future of Precision Medicine is MultimodalThe transition from single-modality to multimodal AI-driven analysis represents a paradigm shift in precision medicine. Organizations that successfully integrate diverse data modalities and multimodal technology will be best positioned to drive better patient outcomes and maximize drug development success.Realizing this potential, however, demands more than technical innovation. It demands systemic transformation across the healthcare landscape — from evolving regulatory frameworks for multimodal CDx to updated reimbursement models, standardized deployment practices, and greater education for both clinicians and patients.For biopharma companies, the path forward is clear:Break Down Data Silos: Support the democratization of access to different data modalities, both in the real-world setting as well as in the clinical trial space.Invest in Multimodal Technology and Expertise: Partner with technology leaders to integrate multimodal approaches into drug development, go-to-market strategies, and post-marketing decision support.Foster Collaborations to Shape the Ecosystem: Engage with regulators, payors, academic institutions, and technology partners to validate, standardize, and endorse multimodal approaches.About twenty years ago, cancer was still considered an organ disease. Looking back today, this may look like distant, medieval times. Twenty years from now, new generations of life sciences professionals may look at 2025 in a disturbingly similar way. The multimodal revolution is only getting started.ReferencesSkoulidis, F. et al. 1325P TRIDENT: Machine learning (ML) multimodal signatures to identify patients that would benefit most from Tremelimumab (T) addition to durvalumab (D) + chemotherapy (CT) with data from the POSEIDON trial. Ann. Oncol. 35, S842–S843 (2024).

Two-thirds (67.4%) of patients treated with IMFINZI-based perioperative regimen remained event-free at two years First and only immunotherapy to demonstrate statistically significant event-free survival in a global Phase III trial in this setting WILMINGTON, DE, USA I June 01, 2025 I Positive results from the MATTERHORN Phase III trial showed perioperative treatment with AstraZeneca’s IMFINZI ® (durvalumab) in combination with standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS) versus chemotherapy alone. Patients were treated with neoadjuvant IMFINZIin combination with chemotherapy before surgery, followed by adjuvant IMFINZI in combination with chemotherapy, then IMFINZI monotherapy. The trial evaluated this regimen versus perioperative chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers. These results will be presented today during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL (abstract #LBA5) and simultaneously published in The New England Journal of Medicine . In a planned interim analysis, patients treated with the IMFINZI-basedperioperative regimen showed a 29% reduction in the risk of disease progression, recurrence or death versus chemotherapy alone (based on an EFS hazard ratio [HR] of 0.71; 95% confidence interval [CI] 0.58-0.86; p<0.001). Estimated median EFS was not yet reached for the IMFINZIarm versus 32.8 months for the comparator arm. An estimated 78.2% of patients treated with the IMFINZI-based perioperative regimen were event-free at one year compared to 74.0% in the comparator arm; the estimated 24-month EFS rate was 67.4% versus 58.5%, respectively, signaling a greater magnitude of benefit over time for the IMFINZI-based regimen. For the secondary endpoint of overall survival (OS), a strong trend was observed in favor of the IMFINZI-basedperioperative regimen (HR=0.78; 95% CI 0.62-0.97; p=0.025). The trial will continue to follow OS, which will be formally assessed at the final analysis. Yelena Y. Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, and principal investigator for the trial, said: “Despite receiving curative-intent surgery and chemotherapy, patients with gastric and gastroesophageal cancers frequently develop recurrent disease. Results from the MATTERHORN trial showed that more than two-thirds of patients treated with a durvalumab-based perioperative regimen had not experienced a recurrence or were progression-free after two years. This new treatment approach should become the new standard of care in this setting based on these results.” Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “This immunotherapy-based perioperative regimen has the potential to change the clinical paradigm in early gastric and gastroesophageal junction cancers based on the reduction in risk of progression, recurrence or death by nearly a third and the strong trend towards improved survival. As the third positive trial of perioperative treatment with IMFINZI across multiple tumor types, the MATTERHORN trial further validates this approach and highlights our commitment to bringing novel therapies to early stages of disease where there is the greatest chance for cure.” Summary of results: MATTERHORN The safety profile for IMFINZIand FLOT chemotherapy was consistent with the known profiles of each medicine, and the percentage of patients that completed surgery was similar compared to chemotherapy alone. Grade 3 or higher adverse events due to any cause were similar between the two arms. In a previously reported interim analysis for the key secondary endpoint of pathologic complete response (pCR), the IMFINZI – based regimen more than doubled the pCR rate compared to neoadjuvant chemotherapy alone (19% versus 7%, odds ratio 3.08; p<0.001). Please see additional Important Safety Information throughout and Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO . You may report side effects related to AstraZeneca products . Notes Gastric and gastroesophageal junction cancers Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-highest leading cause of cancer mortality. 1 Nearly one million new patients were diagnosed with gastric cancer in 2022, with approximately 660,000 deaths reported globally. 1 In many regions, its incidence has been increasing in patients younger than 50 years old, along with other gastrointestinal (GI) malignancies. 2 In 2024, there were approximately 43,000 drug-treated patients in the US, European Union (EU) and Japan with early-stage and locally advanced gastric or GEJ cancer. 3 Approximately 62,000 patients in these regions are expected to be newly diagnosed in this setting by 2030. 4 GEJ cancer is a type of gastric cancer that arises from and spans the area where the esophagus connects to the stomach. 5 Disease recurrence is common in patients with resectable gastric cancer despite undergoing surgery with curative intent and treatment with neoadjuvant/adjuvant chemotherapy. Approximately one in four patients with gastric cancer who undergo surgery develop recurrent disease within one year, and one in four patients do not survive beyond two years, reflecting high unmet medical need. 6-7 Additionally, the five-year survival rate remains poor, with less than half of patients alive at five years. 8 MATTERHORN MATTERHORN is a randomized, double-blind, placebo-controlled, multi-center, global Phase III trial evaluating IMFINZIas perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 948 patients were randomized to receive a 1500mg fixed dose of IMFINZI plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery. This was followed by IMFINZIor placebo every four weeks for up to 12 cycles after surgery (including two cycles of IMFINZIor placebo plus FLOT chemotherapy and 10 additional cycles of IMFINZI or placebo monotherapy). In the MATTERHORN trial, the primary endpoint is EFS, defined as time from randomization until the date of one of the following events (whichever occurred first): RECIST (version 1.1, per blinded independent central review assessment) progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period; RECIST progression/recurrence during the adjuvant period; non-RECIST progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period or discovered during surgery; progression/recurrence confirmed by biopsy post-surgery; or death due to any cause. Key secondary endpoints include pCR rate, defined as the proportion of patients who have no detectable cancer cells in resected tumor tissue following neoadjuvant therapy, and OS. The trial enrolled participants in 176 centers in 20 countries, including in the US, Canada, Europe, South America and Asia. IMFINZI IMFINZI ® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses. IMFINZI is also approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with IMJUDO ® (tremelimumab-actl) in unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in Japan and the EU. In addition to its indications in GI cancers, IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of IMJUDO and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy for the treatment of extensive-stage SCLC. IMFINZI is approved in the US and other countries as a perioperative treatment in combination with neoadjuvant chemotherapy for muscle-invasive bladder cancer based on the NIAGARA Phase III trial. Additionally, IMFINZI plus standard-of-care Bacillus Calmette-Guérin induction and maintenance therapy demonstrated a statistically significant and clinically meaningful improvement in disease-free survival for patients with high-risk non-muscle-invasive bladder cancer in the POTOMAC Phase III trial. IMFINZI in combination with chemotherapy followed by IMFINZI monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). IMFINZI in combination with chemotherapy followed by olaparib and IMFINZI is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan. Since the first approval in May 2017, more than 374,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several gastrointestinal cancers. AstraZeneca in GI cancers AstraZeneca has a broad development program for the treatment of GI cancers across several medicines and a variety of tumor types and stages of disease. In 2022, GI cancers collectively represented approximately 5 million new cancer cases leading to approximately 3.3 million deaths. 9 Within this program, the Company is committed to improving outcomes in gastric, liver, biliary tract, esophageal, pancreatic, and colorectal cancers. In addition to its indications in BTC and HCC, IMFINZIis being assessed in combinations, including with IMJUDO, in liver, esophageal and gastric cancers in an extensive development program spanning early to late-stage disease across settings. Fam-trastuzumab deruxtecan-nxki, a HER2-directed antibody drug conjugate, is approved in the US and several other countries for HER2-positive advanced gastric cancer. Fam-trastuzumab deruxtecan-nxkiis jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. Olaparib, a first-in-class PARP inhibitor, is approved the US and several other countries for the treatment of BRCA- mutated metastatic pancreatic cancer. Olaparib is developed and commercialized by AstraZeneca and Merck & Co., Inc., known as MSD outside the US and Canada. The Company is also assessing rilvegostomig (AZD2936), a PD-1/TIGIT bispecific antibody, in combination with chemotherapy as an adjuvant therapy in BTC, in combination with bevacizumab with or withoutIMJUDO as a 1st-line treatment in patients with advanced HCC, and as a 1st-line treatment in patients with HER2-negative, locally advanced unresectable or metastatic gastric and GEJ cancers. Rilvegostomig is also being evaluated in combination with fam-trastuzumab deruxtecan-nxki in previously untreated, HER2-expressing, locally advanced or metastatic BTC. AstraZeneca is advancing multiple modalities that provide complementary mechanisms for targeting Claudin 18.2, a promising therapeutic target in gastric cancer. These include sonesitatug vedotin, a potential first-in-class antibody drug conjugate licensed from KYM Biosciences Inc., currently in Phase III development; AZD5863, a novel Claudin 18.2/CD3 T-cell engager bispecific antibody licensed from Harbour Biomed in Phase I development; and AZD6422, an armored autologous chimeric antigen receptor T-cell (CAR T) therapy, currently being evaluated in an investigator-initiated trial (IIT) in collaboration with AbelZeta in China. In early development, AstraZeneca is developing two Glypican 3 (GPC3) armored CAR Ts in HCC. AZD5851, currently in Phase I development, is being developed globally, and C-CAR031 / AZD7003 is being co-developed with AbelZeta in China where it is under evaluation in an IIT. AstraZeneca in immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with IMJUDO as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. 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 catalyze 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. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca . References SOURCE: AstraZeneca