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Phase 3 DESTINY-Lung04 trial shows first-line trastuzumab deruxtecan improves progression-free survival in her2-mutant NSCLC. Posted date September 14, 2026 A new study led by researchers at Dana-Farber Cancer Institute found that first-line trastuzumab deruxtecan (T-DXd) significantly improved progression-free survival compared with pembrolizumab plus platinum-based chemotherapy in patients with advanced or metastatic HER2-mutant non-small cell lung cancer (NSCLC). The findings suggest T-DXd could become a new first-line treatment option for this patient population. The results were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) in SEOUL, Republic of Korea on Sept. 14, 2026, by Julia Rotow, MD, clinical director of the Lowe Center for Thoracic Oncology and director of clinical research in thoracic oncology at Dana-Farber. DESTINY-Lung04 is the first global randomized phase 3 trial to show that a HER2-directed therapy can outperform standard first-line chemoimmunotherapy in patients with HER2-mutant NSCLC. In the trial, median progression-free survival by blinded independent central review was 14.3 months with T-DXd, compared with 8.3 months with pembrolizumab plus chemotherapy, representing a 37% reduction in the risk of progression or death. "DESTINY-Lung04 is the first phase 3 trial to demonstrate the benefit of a HER2-directed therapy vs global standard of care as upfront treatment for patients with HER2-mutant NSCLC," said Rotow. The study enrolled 454 previously untreated patients with unresectable locally advanced or metastatic nonsquamous NSCLC harboring HER2 exon 19 or exon 20 mutations. Patients were randomly assigned to receive either single-agent T-DXd every three weeks or pembrolizumab plus platinum chemotherapy and pemetrexed. T-DXd also produced higher response rates than pembrolizumab plus chemotherapy. The objective response rate was 70.0% with T-DXd versus 44.5% with standard treatment, and median duration of response was 13.4 months versus 9.7 months. "These results demonstrate substantial improvements in progression-free survival and response with first-line trastuzumab deruxtecan for patients with advanced or metastatic HER2-mutant NSCLC," said Rotow. "The findings support T-DXd as a new first-line treatment option for this patient population, for whom more effective HER2-directed approaches are needed." Median overall survival was 29.3 months with T-DXd and 33.1 months with pembrolizumab plus chemotherapy, though investigators noted that differences in subsequent therapies between the groups complicated interpretation. The DESTINY-Lung04 findings support first-line T-DXd as an important new treatment option for patients with HER2-mutant NSCLC. Lung Cancers Lung Cancer, non-small cell Related Doctors and Researchers Media Contacts If you are a journalist and have a question about this story, please call 617-632-4090 and ask to speak to a member of the media team, or email [email protected]. The Media Team cannot respond to patient inquiries. For more information, please see Contact Us. Julia Rotow, MD

Command palette. 5 hours ago Researchers from St. Jude Children's Research Hospital, the University of Pavia, Dana-Farber Cancer Institute, and Harvard Medical School have unveiled AdaptiveFlow, an open-source artificial intelligence platform engineered to transform ultra-large-scale virtual drug screening. Published this week in Nature Biotechnology, the framework eliminates longstanding computational bottlenecks by enabling the routine examination of billions of drug-like molecules while cutting processing costs by a factor of one thousand compared to conventional methods. The platform achieves unprecedented scalability through an architecture that maintains linear performance efficiency across up to 5.6 million virtual central processing units. This design circumvents the communication overhead that typically degrades high-performance computing systems as processor counts rise. AdaptiveFlow centers on an eighteen-dimensional computational grid, with each axis encoding a specific molecular characteristic. This multidimensional mapping allows automated prioritization of chemically diverse candidates, which are filtered through a machine-learning classifier trained on prescreening outputs. The system integrates more than fifteen hundred molecular docking protocols to evaluate and rank compounds based on predicted target binding affinity. To demonstrate practical utility, the development team executed a virtual screen of sixty-nine billion molecules, establishing the largest ready-to-dock library utilized in a single discovery campaign. AdaptiveFlow successfully isolated high-affinity inhibitors for poly(ADP-ribose) polymerase 1, a validated oncology target, and ferroptosis suppressor protein 1, an emerging target implicated in cancer cell survival. The successful targeting of FSP1, which features a structurally complex binding pocket containing an additional cofactor, confirms the platform's capability to navigate challenging pharmacological environments. Initial candidate quality from AdaptiveFlow consistently surpassed traditional screening outputs, substantially shortening the lead optimization timeline. By merging advanced machine learning with massively parallel cloud infrastructure, the platform democratizes access to comprehensive chemical space exploration. The creators emphasize that removing cost and technical barriers will accelerate therapeutic pipeline development, particularly for historically intractable biological targets. The entire framework, along with implementation documentation and usage tutorials, is available free of charge on GitHub and the official project repository. AdaptiveFlow marks a definitive transition toward scalable, economically viable computational drug discovery, enabling research institutions to systematically convert massive chemical datasets into clinically viable therapeutics. This news is intelligently aggregated by AI to deliver industry updates efficiently. It does not constitute opinions or advice.

PICI invests more than $1 million in five Early Career researchers advancing the future of Cancer Immunotherapy. PICI has now awarded more than $23.9 million total to fund 63 research projects in the last decade, powering the next generation of cancer immunotherapies SAN FRANCISCO - August 19, 2026 - The Parker Institute for Cancer Immunotherapy (PICI) today announced its 2026 class of Early Career Researcher awardees. The five investigators selected this year will receive more than $1 million in combined funding to advance innovative research projects that leverage cutting-edge scientific approaches that will accelerate the development of next-generation immunotherapies for cancer patients. Now in its tenth year, PICI's Early Career Researcher Awards program has invested $23.9 million across 63 research projects. Beyond funding, the program provides promising scientists with access to PICI's collaborative research network and world-class scientific resources, empowering them to pursue bold, high-risk, high-reward ideas that have the potential to transform cancer treatment. "Some of the most transformative advances in cancer research begin with scientists willing to ask difficult questions and pursue ideas that challenge conventional thinking," said Dr. Karen Knudsen, CEO of PICI. "The Early Career Researcher Awards give these emerging leaders the resources, community and support to take their ideas further. We're excited to invest in this exceptional group of scientists and in the discoveries they may bring to patients." Four of this year's awardees are Parker Scholars, early career scientists entering their first postdoctoral appointment in a high-impact area of cancer immunotherapy. PICI has also recognized one Parker Bridge Fellow, an investigator who recently completed their MD or PhD and is ready to establish a laboratory or independent program in cancer immunotherapy. * Parker Scholar Sophie Louise Gray-Gaillard of the University of Pennsylvania is investigating how the spatial organization of the tumor microenvironment shapes tumor-infiltrating CD8 T lymphocyte function. Ms. Gray-Gaillard will study the cellular interactions and molecular signals that distinguish tumor-specific T cells from nontumor-specific "bystander" T cells, to inform more precise immunotherapeutic strategies for cancer patients. * Parker Scholar Jingya Qiu, PhD, of Gladstone Institutes is investigating how immune responses within tissue microenvironments contribute to cancer initiation. Dr. Qiu will use spatiotemporal imaging and digital pathology to understand how premalignant tissues interact with the immune system, with the goal of developing immune-based strategies for early cancer detection and intervention before cancer progresses to invasive disease. * Parker Scholar Xinyu Xiang of Stanford Medicine is developing a new platform to generate T cell receptor mimetics that can recognize tumor-associated peptide-MHC complexes with high specificity. Ms. Xiang will integrate protein engineering, synthetic co-evolution, and machine learning to systematically discover new binders and expand the range of cancer targets that can be recognized by targeted immunotherapies. * Parker Scholar Shaobo Yang, PhD, of Dana-Farber Cancer Institute is developing programmable bacterial "living medicines" for solid tumors. Dr. Yang will advance the Living Immune Modulating Engager (LIME) platform, using tumor-homing bacteria to connect cancer cells with T cells or natural killer cells directly within tumors and enhance responses to RAS-targeted therapy. * Parker Bridge Fellow Maxime Meylan, PhD, of Dana-Farber Cancer Institute is investigating how the organization of the tumor microenvironment shapes T-cell responses in cancer. Dr. Meylan will study how tumor cell states and spatial tissue organization create barriers to T-cell infiltration in triple-negative breast cancer, to identify strategies to overcome immune exclusion. Since 2016, PICI's Early Career Researcher program has awarded scientists from a highly competitive field of applicants across PICI's network of leading cancer research centers. Awardees are selected based on their project's proposed scientific approach, the potential impact it will have on the field of cancer immunotherapy, and its alignment with PICI's mission to develop and accelerate access to breakthrough cancer therapies in order to turn all cancers into curable diseases.